研究者情報

マスター

アカウント（マスター）

• 氏名

  細川　雅史(ホソカワ　マサシ), ホソカワ　マサシ

所属（マスター）

• 水産科学研究院　海洋応用生命科学部門　生物資源化学分野

所属（マスター）

• 水産科学研究院　海洋応用生命科学部門　生物資源化学分野

独自項目

syllabus

• 2021, 生物資源化学特論Ⅰ, Advanced Marine Bioresources Chemistry Ⅰ, 修士課程, 水産科学院, 水産化学　海洋天然物化学　分析化学　分子栄養学　ケミカルバイオロジー　マリンバイオテクノロジー　アミノ酸　カロテノイド　脂質　生理活性物質　未利用資源
• 2021, 環境と人間, Environment and People, 学士課程, 全学教育, 生物資源，資源利用，機能性，マリンバイオマス，環境保全，マリンバイオテクノロジー，有効利用，高度利用，ゼロエミッション，SDGs
• 2021, 健康と社会, Health and Society, 学士課程, 全学教育, 魚、海藻、食生活、加工保蔵、嗜好性、栄養成分、機能性、健康、安全性
• 2021, 水産生物化学, Biochemistry of Fisheries Sciences, 学士課程, 水産学部, 水産食品，化成品，魚貝類，藻類，食品加工，変性，酸化，タンパク質，脂質，糖質，ヌクレオチド，核酸，エキス成分，色素成分，臭気成分，食品機能，
• 2021, 分子栄養学, Molecular Nutrition Biochemistry, 学士課程, 水産学部, 分子生物学、栄養化学、機能性食品成分、生理活性物質、遺伝子発現、受容体
• 2021, 栄養化学, Nutritional Chemistry, 学士課程, 水産学部, 栄養素、食物、消化・吸収・代謝、健康、水産食品
• 2021, 教科教育法（理科I）, Teaching Method of School Subjects(Science Ⅰ), 学士課程, 教育学部

PositionHistory

• 大学院水産科学研究院副研究院長, 2022年4月1日, 2024年3月31日

researchmap

プロフィール情報

学位

• 博士（水産学）（北海道大学）

プロフィール情報

• 姓

  細川, ホソカワ

• 名

  雅史, マサシ

• ID各種

  200901013802521530

対象リソース

https://fish-hokudai-bfmc.labby.jp/

業績リスト

研究キーワード

• n-3系高度不飽和脂肪酸   炎症予防物質   アスタキサンチン   フコキサンチン   EPA   DHA   カロテノイド   リン脂質   生活習慣病予防   Lipid Biochemistry   Food Chemistry   Molecular Nutrition   Fisheries Sciences   

研究分野

• ライフサイエンス / 水圏生産科学
• ライフサイエンス / 分子生物学
• ライフサイエンス / 食品科学
• ライフサイエンス / 水圏生命科学

経歴

• 2017年04月 - 現在 北海道大学 大学院水産科学研究院 生物資源化学講座 教授
• 2009年 - 2017年03月 北海道大学 水産科学研究科(研究院) 准教授

委員歴

• 2018年 - 現在   日本農芸化学会   代議員
• 2017年11月 - 現在   日本栄養食糧学会   代議員
• 2015年 - 現在   日本肥満学会   評議員
• 2013年 - 現在   日本油化学会   学術専門委員
• 2012年 - 現在   日本食品科学工学会   英文誌編集委員
• 2004年 - 現在   日本油化学会   国際交流委員
• 2016年 - 2022年   日本水産学会   出版委員会委員（2018-2019副委員長, 2020-委員長）
• 2004年 - 2020年   日本油化学会   関東支部 企画委員   日本油化学会
• 2015年03月 - 2018年   日本農芸化学会学術活動強化委員
• 2012年 - 2015年03月   日本農芸学会   北海道支部幹事
• 2012年   日本栄養食糧学会   支部参与
• 2012年   日本油化学会   関東支部評議員
• 2008年   脂質栄養学会   評議員   脂質栄養学会
• 2002年 - 2006年   日本油化学会   若手の会 幹事   日本油化学会
• 2003年 - 2005年   日本水産学会   若手の会 幹事   日本水産学会
• 2002年 - 2004年   日本水産学会   支部庶務幹事   日本水産学会

受賞

• 2024年04月 日本油化学会 令和5年度日本油化学会賞
   水産脂溶性成分の有効利用を目指した分子栄養学的研究 

  受賞者: 細川雅史
• 2014年 アスタキサンチン研究会 第9回 Astaxanthin Award
   

  受賞者: 細川 雅史
• 2012年 日本油化学会 WCOS2012 Outstanding Poster Presentation Award
   

  受賞者: 細川 雅史
• 2007年 平成18年度日本油化学会進歩賞
  
• 2003年 The American Oil Chemists' Society, Biotechnology Division, Outstanding Paper Presentation.
  
• 2003年 The American Oil Chemists' Society, Health & Nutrition Devision, Best Overall Poster Award.
  
• 2002年 平成14年度 日本油化学会オレオサイエンス賞
  
• 2001年 平成13年度 日本水産学会奨励賞
  

論文

• Identification of a novel monocyclic carotenoid and prediction of its biosynthetic genes in Algoriphagus sp. oki45.

  Naoki Takatani, Takashi Maoka, Tomoo Sawabe, Fumiaki Beppu, Masashi Hosokawa

  Applied microbiology and biotechnology 108 1 102 - 102 2024年12月 

  Bacteria belonging to the genus Algoriphagus have been isolated from various sources, such as Antarctic sea ice, seawater, and sediment, and some strains are known to produce orange to red pigments. However, the pigment composition and biosynthetic genes have not been fully elucidated. A new red-pigmented Algoriphagus sp. strain, oki45, was isolated from the surface of seaweed collected from Senaga-Jima Island, Okinawa, Japan. Genome comparison revealed oki45's average nucleotide identity of less than 95% to its closely related species, Algoriphagus confluentis NBRC 111222 T and Algoriphagus taiwanensis JCM 19755 T. Comprehensive chemical analyses of oki45's pigments, including 1H and 13C nuclear magnetic resonance and circular dichroism spectroscopy, revealed that the pigments were mixtures of monocyclic carotenoids, (3S)-flexixanthin ((3S)-3,1'-dihydroxy-3',4'-didehydro-1',2'-dihydro-β,ψ-caroten-4-one) and (2R,3S)-2-hydroxyflexixanthin ((2R,3S)-2,3,1'-trihydroxy-3',4'-didehydro-1',2'-dihydro-β,ψ-caroten-4-one); in particular, the latter compound was new and not previously reported. Both monocyclic carotenoids were also found in A. confluentis NBRC 111222 T and A. taiwanensis JCM 19755 T. Further genome comparisons of carotenoid biosynthetic genes revealed the presence of eight genes (crtE, crtB, crtI, cruF, crtD, crtYcd, crtW, and crtZ) for flexixanthin biosynthesis. In addition, a crtG homolog gene encoding 2,2'-β-hydroxylase was found in the genome of the strains oki45, A. confluentis NBRC 111222 T, and A. taiwanensis JCM 19755 T, suggesting that the gene is involved in 2-hydroxyflexixanthin synthesis via 2-hydroxylation of flexixanthin. These findings expand our knowledge of monocyclic carotenoid biosynthesis in Algoriphagus bacteria. KEY POINTS: • Algoriphagus sp. strain oki45 was isolated from seaweed collected in Okinawa, Japan. • A novel monocyclic carotenoid 2-hydroxyflexixanthin was identified from strain oki45. • Nine genes for 2-hydroxyflexixanthin biosynthesis were found in strain oki45 genome.
• Identification of the Active EPA/AA-Binding Ether-Type Phosphatidylcholine Derived from the Starfish Patiria pectinifera for C2C12 Myotube Growth

  Aoi Fukushima, Kyosuke Imamura, Naoki Takatani, Masashi Hosokawa, Fumiaki Beppu

  ACS Omega 2024年11月12日
• Dietary 7,10-dihydroxy-8(E)-octadecenoic acid reduces fat accumulation and prevents hyperglycemia and hyperlipidemia in diabetic/obese KK-Ay mice

  Fumiaki Beppu, Shota Fuji, Hak-Ryul Kim, Ching T. Hou, Kazuo Miyashita, Masashi Hosokawa

  BIOCATALYSIS AND AGRICULTURAL BIOTECHNOLOGY 61 2024年10月 

  7,10-Dihydroxy-8(E)-octadecenoic acid (DOD) is a dihydroxy fatty acid produced by Pseudomonas aeruginosa PR3 from oleic acid. Present study investigated preventive effects of dietary DOD on obesity, hyperlipidemia and hyperglycemia in diabetic/obese KK-A(y) mice. After one week of acclimation, mice (5-week-old) were divided three groups fed with AIN-93G-based high fat diet (20% fat, w/w) as follows; Control group: 3% soybean oil + 17% lard, DOD 1% group: 3% soybean oil + 16% lard +1% DOD, DOD 2% group: 3% soybean oil + 15% lard + 2% DOD. Four weeks feeding with 1% and 2% DOD diets suppressed body weight gain and visceral fat accumulation, and improved blood glucose and serum lipids levels as well as hepatic lipid accumulation compared to control group. RT-PCR analysis revealed no changes were observed in mRNA of adiponectin (Adipoq) and proinflammatory TNF-alpha (Tnfa) and MCP-1 (Ccl2), but a decreasing trend in leptin mRNA expression in mesenteric white adipose tissue (WAT), suggesting that suppressed fat accumulation by DOD contribute to prevention of over production of leptin. We also observed a reduction of mRNA expression of hepatic insulin-target gluconeogenic enzymes such as PEPCK and G6Pase and the transcription factor sterol regulatory element-binding protein-1. These results showed that dietary DOD is effective to improve glucose and lipid metabolism in KK-A(y )mice. The present study provides new insights showing potential use of dihydroxy fatty acids as functional lipids.
• Apo-12'-capsorubinal exhibits anti-inflammatory effects and activates nuclear factor erythroid 2-related factor 2 in RAW264.7 macrophages.

  Naoki Takatani, Hiroki Miyafusa, Yumiko Yamano, Fumiaki Beppu, Masashi Hosokawa

  Archives of biochemistry and biophysics 760 110125 - 110125 2024年08月16日 

  Apocarotenoids have short carbon chain structures cleaved at a polyene-conjugated double bond. They can be biosynthesized in plants and microorganisms. Animals ingest carotenoids through food and then metabolize them into apocarotenoids. Although several apocarotenoids have been identified in the body, their precise health functions are still poorly understood. This study investigated the anti-inflammatory activities of apo-12'-capsorubinal in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. It was confirmed that apo-12'-capsorubinal was not cytotoxic to the macrophages at the concentrations tested. Apo-12'-capsorubinal treatment led to a marked downregulation of interleukin (IL)-6 protein and Il6 mRNA levels. This apocarotenoid exhibited more potent inhibitory effects than its parent carotenoids, capsanthin and capsorubin. Furthermore, apo-12'-capsorubinal, but not its parent carotenoids, promoted the nuclear accumulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and upregulated the expression of Nrf2-target genes, such as heme oxygenase 1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO-1), in a dose-dependent manner. Furthermore, a comparison using apo-12'-zeaxanthinal and 7,8-dihydro-8-oxo-apo-12'-zeaxanthinal revealed that the α, β-unsaturated carbonyl group on the polyene linear chain mediated the enhanced nuclear Nrf2 translocation, HO-1 expression, and inhibition of IL-6 production. In contrast, apo-12'-mytiloxanthinal, which harbored a hydroxyl group at C-8 of apo-12'-capsorubinal, did not exhibit any of these activities. These results indicated that the β carbon of the α, β-unsaturated carbonyl group in the linear part of the polyene chain is crucial to the Nrf2-activating and anti-inflammatory effects of apo-12'-capsorubinal. This study will advance our knowledge of the physiological significance of xanthophyll-derived apocarotenoids and their potential use as nutraceuticals and pharmaceuticals.
• Identification and tissue distribution of fucoxanthinol and amarouciaxanthin A fatty acid esters in fucoxanthin-fed mice

  Naoki Takatani, Kana Sakimura, Kodai Nagata, Fumiaki Beppu, Yumiko Yamano, Takashi Maoka, Masashi Hosokawa

  Food Chemistry 410 2023年06月01日 

  Administered carotenoid fatty acid esters are thought to be hydrolyzed to their free forms and absorbed into the body, and information on the tissue distribution of carotenoid fatty acid esters has been limited. Fucoxanthin, a marine carotenoid, exhibits various health benefits, including anti-diabetic and anti-obesity effects. However, fucoxanthin metabolism in mammals remains unclear. Herein, we investigated the fatty acid esters of fucoxanthin metabolites, fucoxanthinol and amarouciaxanthin A, in the tissues of male C57BL/6J mice fed a fucoxanthin-containing diet for one week. Fucoxanthinol and amarouciaxanthin A-3-esters accumulated abundantly in the liver and epididymal white adipose tissue, respectively. These esters were less detectable in the serum and other tissues. Therefore, it is suggested that fucoxanthinol and amarouciaxanthin A are partially acylated in the liver and epididymal white adipose tissue after being transported through the body as their free forms. This study presents a novel carotenoid metabolic pathway in mammals.
• Dietary Combination of Fish Oil and Soy β-Conglycinin Inhibits Fat Accumulation and Reduces Blood Glucose Levels by Altering Gut Microbiome Composition in Diabetic/Obese KK-<i>A</i> ^<i>y</i> Mice

  Satoshi Wanezaki, Takumi Taniwaki, Junki Miyamoto, Masashi Hosokawa

  Journal of Oleo Science 72 3 303 - 312 2023年
• Identification and tissue distribution of fucoxanthinol and amarouciaxanthin A fatty acid esters in fucoxanthin-fed mice.

  Naoki Takatani, Kana Sakimura, Kodai Nagata, Fumiaki Beppu, Yumiko Yamano, Takashi Maoka, Masashi Hosokawa

  Food chemistry 410 135318 - 135318 2022年12月28日 

  Administered carotenoid fatty acid esters are thought to be hydrolyzed to their free forms and absorbed into the body, and information on the tissue distribution of carotenoid fatty acid esters has been limited. Fucoxanthin, a marine carotenoid, exhibits various health benefits, including anti-diabetic and anti-obesity effects. However, fucoxanthin metabolism in mammals remains unclear. Herein, we investigated the fatty acid esters of fucoxanthin metabolites, fucoxanthinol and amarouciaxanthin A, in the tissues of male C57BL/6J mice fed a fucoxanthin-containing diet for one week. Fucoxanthinol and amarouciaxanthin A-3-esters accumulated abundantly in the liver and epididymal white adipose tissue, respectively. These esters were less detectable in the serum and other tissues. Therefore, it is suggested that fucoxanthinol and amarouciaxanthin A are partially acylated in the liver and epididymal white adipose tissue after being transported through the body as their free forms. This study presents a novel carotenoid metabolic pathway in mammals.
• Monocaprin Enhances Bioavailability of Fucoxanthin in Diabetic/Obese KK-Ay Mice

  Kodai Nagata, Naoki Takatani, Fumiaki Beppu, Aya Abe, Etsuko Tominaga, Tomohisa Fukuhara, Makoto Ozeki, Masashi Hosokawa

  Marine Drugs 20 7 446 - 446 2022年07月07日 [査読有り]
   

  Fucoxanthin is a marine carotenoid found in brown seaweeds and several microalgae. It has been reported that fucoxanthin has health benefits such as anti-obesity and anti-diabetic effects. To facilitate fucoxanthin applications in the food industry, it is important to improve its low bioavailability. We attempted the combined feeding of fucoxanthin-containing seaweed oil (SO) and monocaprin in a powder diet and analyzed the fucoxanthin metabolite contents in the liver, small intestine and serum of diabetic/obese KK-Ay mice. After 4 weeks of feeding with the experimental diets, the serum fucoxanthinol concentrations of the mice fed 0.2% SO and 0.5% monocaprin were higher than those of the 0.2% SO-fed mice. Furthermore, fucoxanthinol accumulation in the liver and small intestine tended to increase in a combination diet of 0.2% SO and 0.125–0.5% monocaprin compared with a diet of 0.2% SO alone, although amarouciaxanthin A accumulation was not different among the 0.2% SO-fed groups. These results suggest that a combination of monocaprin with fucoxanthin-containing SO is an effective treatment for improving the bioavailability of fucoxanthin.
• Preparation of Apoastaxanthinals and Evaluation of Their Anti-inflammatory Action against Lipopolysaccharide-Stimulated Macrophages and Adipocytes

  Naoki Takatani, Fumiaki Beppu, Yumiko Yamano, Takashi Maoka, Kazuo Miyashita, Masashi Hosokawa

  ACS OMEGA 2022年06月 [査読有り]
   

  Apocarotenoids are carotenoid derivatives in which the polyene chain is cleaved via enzymatic or nonenzymatic action. They are found in animal tissues and carotenoid-containing foods. However, limited information on the biological functions of apocarotenoids is available. Here, we prepared apocarotenoids from astaxanthin via chemical oxidation and evaluated their anti-inflammatory action against macrophages and adipocytes. A series of astaxanthin-derived apoastaxanthinals, apo-11-, apo-15-, apo-14'-, apo-12'-, apo-10'-, and apo-8'astaxanthinals, were successfully characterized by chromatography and spectroscopic analysis. The apoastaxanthinals inhibited inflammatory cytokine production and mRNA expression against lipopolysaccharide-stimulated RAW 264.7 macrophages. Apoastaxanthinals suppressed interleukin-6 overexpression in an in vitro model with macrophages and adipocytes in the following cultures: (1) contact coculture of 3T3-L1 adipocytes and RAW264.7 macrophages and (2) 3T3-L1 adipocytes in a RAW264.7-derived conditioned media. These results indicate that the apoastaxanthinals have the potential for regulation of adipose tissue inflammation observed in obesity.
• Reduction of serum lipid levels in diabetic obese KK-A ^y mice using monoalkyldiacylglycerol-rich oil derived from Berryteuthis magister

  Masaki Kakimoto, Naoki Takatani, Masashi Hosokawa, Fumiaki Beppu

  Fisheries Science 2022年 

  Monoalkyldiacylglycerol (MADG), an ether analog of triacylglycerols, is abundant in some marine animals such as deep-sea sharks and echinoderms. The present study aims to investigate the effects of an MADG-rich neutral lipid derived from Berryteuthis magister (MNB) on the lipid metabolism of diabetic/obese KK-Ay mice. Male mice (5 weeks old) were fed soybean oil (control group), MNB, or fish oil (FO) which contain the same amount of EPA and DHA in the form of triacylglycerols. MNB or FO supplementation resulted in a decrease in adipose tissue weights and blood glucose levels compared to the control mice. Interestingly, serum lipid levels in the MNB group were significantly lower than those of the control and FO groups. Although there was no difference in EPA and DHA levels in the tissues between the FO and MNB groups, a decrease in the number of lipoprotein particles was characteristically observed in the mice fed with MNB. Our results suggest that the MADG structure-dependent effect on lipoprotein synthesis and/or secretion partly accounted for the reduced serum lipids in KK-Ay mice by dietary MNB. This study advances the understanding of MADG as a nutraceutical and provides insights into the role of ether lipids in lipoprotein metabolism that can contribute to the development of prevention and treatment strategies for hyperlipidemia.
• n-3 Polyunsaturated fatty acid-enriched phosphatidylglycerol suppresses inflammation in RAW264.7 cells through Nrf2 activation via alteration of fatty acids in cellular phospholipids

  Liping Chen, Fumiaki Beppu, Naoki Takatani, Kazuo Miyashita, Masashi Hosokawa

  FISHERIES SCIENCE 87 5 727 - 737 2021年09月 [査読有り]
   

  Phosphatidylglycerol (PG) is a naturally occurring phospholipid. The immunomodulatory activity of PG has been reported to be dependent on its fatty acid composition. In this study, the anti-inflammatory effect of n-3 polyunsaturated fatty acid-enriched PG (n-3 PUFA-PG) was investigated on macrophage-like RAW264.7 cells stimulated by lipopolysaccharide (LPS). n-3 PUFA-PG binding eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) significantly suppressed interleukin-6, interleukin-1 beta and nitric oxide production by RAW264.7 cells. Notably, the suppressive effect of n-3 PUFA-PG on inflammatory factor production was more potent compared to n-3 PUFA-phosphatidylcholine (PC) and soybean PG. n-3 PUFA-PG treatment markedly increased EPA and DHA in intracellular PC and phosphatidylethanolamine and decreased 18:1n-9 through downregulation of fatty acid synthase and stearoyl-CoA desaturase mRNA expression compared to n-3 PUFA-PC treatment. Furthermore, n-3 PUFA-PG enhanced nuclear factor erythroid E2-related factor (Nrf2) levels in the nucleus and increased heme oxygenase-1 mRNA expression. N-acetyl-L-cysteine, which is an inhibitor against Nrf-2 activation, alleviated the induction of HO-1 mRNA and anti-inflammatory effect of n-3 PUFA-PG. These data suggest that n-3 PUFA-PG exhibits anti-inflammatory effects on LPS-stimulated RAW264.7 cells through Nrf2 activation by altering cellular fatty acids.
• Seco-type β-Apocarotenoid Generated by β-Carotene Oxidation Exerts Anti-inflammatory Effects against Activated Macrophages.

  Naoki Takatani, Fumiaki Beppu, Yumiko Yamano, Takashi Maoka, Masashi Hosokawa

  Journal of oleo science 70 4 549 - 558 2021年04月02日 [査読有り]
   

  β-Apocarotenoids are the cleavage products of β-carotene. They are found in plants, carotenoid-containing foods, and animal tissues. However, limited information is available regarding the health benefits of β-apocarotenoids. Here, we prepared seco-type β-apocarotenoids through the chemical oxidation of β-carotene and investigated their anti-inflammatory effects against activated macrophages. Oxidation of β-carotene with potassium permanganate produced seco-β-apo-8'-carotenal, in which one end-group formed an "open" β-ring and the other was cleaved at the C-7',8' position. In lipopolysaccharide-stimulated murine macrophage-like RAW264.7 cells, seco-β-apo-8'-carotenal inhibited the secretion and mRNA expression of inflammatory mediators such as nitric oxide, interleukin (IL)-6 and IL-1β, and monocyte chemoattractant protein-1. Furthermore, seco-β-apo-8'-carotenal suppressed phosphorylation of c-Jun N-terminal kinase and the inhibitor of nuclear factor (NF)-κB as well as the nuclear accumulation of NF-κB p65. Notably, since seco-β-apo-8'-carotenal exhibited remarkable anti-inflammatory activity compared with β-apo-8'-carotenal, its anti-inflammatory action could depend on the opened β-ring structure. These results suggest that seco-β-apo-8'-carotenal has high potential for the prevention of inflammation-related diseases.
• Effects of Fucoxanthin on the Inhibition of Dexamethasone-Induced Skeletal Muscle Loss in Mice

  Maki Yoshikawa, Masashi Hosokawa, Kazuo Miyashita, Hoyoku Nishino, Takeshi Hashimoto

  NUTRIENTS 13 4 2021年04月 [査読有り]
   

  Fucoxanthin (Fx) has preventive effect against muscle atrophy and myotube loss in vitro, but it has not yet been examined in vivo. Therefore, we aimed to investigate the effect of Fx on dexamethasone (Dex)-induced muscle atrophy and fat mass in mice. ICR mice were fed with Fx diets from 2 weeks before Dex treatment to the end of the study. Muscle atrophy was induced in the mice by oral administration of Dex. Body weight was significantly lower by Dex treatment. Visceral fat mass in the Fx-treated group were significantly lower than those in the control group. The Dex-induced decrease in tibialis anterior muscle mass was ameliorated by Fx treatment. Fx treatment significantly attenuated muscle lipid peroxidation compared with the control and Dex-treated groups. The phosphorylation of AMPK was significantly higher in the Dex-treated group than in the control group. The expression of cytochrome c oxidase (COX) IV was significantly higher in the Fx-treated group than in the control group. These results suggest that Fx may be a beneficial material to prevent muscle atrophy in vivo, in addition to the effect of fat loss.
• Health-Promoting Functions of the Marine Carotenoid Fucoxanthin

  Masashi Hosokawa

  CAROTENOIDS: BIOSYNTHETIC AND BIOFUNCTIONAL APPROACHES 1261 273 - 284 2021年 [査読無し][招待有り]
   

  Fucoxanthin (Fx) is a marine carotenoid found in brown seaweeds and several marine microalgae. Recent studies have reported that dietary Fx exhibits many health-promoting functions such as anti-obesity and anti-diabetic effects in animal experiments. A human clinical trial of Fx showed high potential on reduction of body weight and fat content. The anti-obesity effect of Fx is due to several mechanisms, which include the suppression of adipocyte differentiation, anti-inflammation, and uncouple protein 1 induction in white adipose tissue. Furthermore, Fx reduced blood glucose level and improved insulin resistance through the regulation of adipokine mRNA expressions. In this chapter, we reviewed health beneficial effects and safety of Fx and discussed their molecular mechanisms.
• Identification of Paracentrone in Fucoxanthin-Fed Mice and Anti-Inflammatory Effect against Lipopolysaccharide-Stimulated Macrophages and Adipocytes

  Naoki Takatani, Daisuke Taya, Ami Katsuki, Fumiaki Beppu, Yumiko Yamano, Akimori Wada, Kazuo Miyashita, Masashi Hosokawa

  MOLECULAR NUTRITION & FOOD RESEARCH 65 2 e2000405  2021年01月 [査読有り]
   

  Scope Fucoxanthin is converted to fucoxanthinol and amarouciaxanthin A in the mouse body. However, further metabolism such as cleavage products (i.e., apocarotenoids) remains unclear. The fucoxanthin-derived apocarotenoid in vivo is investigated and the anti-inflammatory effect of apocarotenoids with fucoxanthin partial structure such as allenic bond and epoxide residue against activated macrophages and adipocytes in vitro is evaluated.Methods and Results LC-MS analysis indicates the presence of paracentrone, a C-31-allenic-apocarotenoid, in white adipose tissue of diabetic/obese KK-A(y) and normal C57BL/6J mice fed 0.2% fucoxanthin diet for 1 week. In lipopolysaccharide-activated RAW264.7 macrophages, paracentrone as well as C-26- and C-28-allenic-apocarotenoids suppresses the overexpression of inflammatory factors. Further, apo-10 '-fucoxanthinal, a fucoxanthin-derived apocarotenoid which retained epoxide residue, exhibits a most potent anti-inflammatory activity through regulating mitogen-activated protein kinases and nuclear factor-kappa B inflammatory signal pathways. In contrast, beta-apo-8 '-carotenal without allenic bond and epoxide residue lacks suppressed inflammation. In 3T3-L1 adipocytes, paracentrone, and apo-10 '-fucoxanthinal downregulate the mRNA expression of proinflammatory mediators and chemokines induced by co-culture with RAW264.7 cells.Conclusion Dietary fucoxanthin accumulates as paracentrone as well as fucoxanthinol and amarouciaxanthin A in the mouse body. Allenic bond and epoxide residue of fucoxanthin-derived apocarotenoids have pivotal roles for anti-inflammatory action against activated macrophages and adipocytes.
• Black chokeberry (Aronia melanocarpa) juice residue and its ethanol extract decrease serum lipid levels in high‑fat diet‑fed C57BL/6J mice

  Nana Mikami, Yukie Hosotani, Tomoko Saso, Tomoki Ohta, Kazuo Miyashita, Masashi Hosokawa

  International Journal of Functional Nutrition 1 2 2020年10月30日 [査読有り]
  
• Ecogenomics of the Marine Benthic Filamentous Cyanobacterium Adonisia

  Juline M. Walter, Felipe H. Coutinho, Luciana Leomil, Paulo I. Hargreaves, Mariana E. Campeao, Veronica V. Vieira, Beatriz S. Silva, Giovana O. Fistarol, Paulo S. Salomon, Tomoo Sawabe, Sayaka Mino, Masashi Hosokawa, Hideaki Miyashita, Fumito Maruyama, Marcel C. van Verk, Bas E. Dutilh, Cristiane C. Thompson, Fabiano L. Thompson

  MICROBIAL ECOLOGY 80 2 249 - 265 2020年08月 [査読有り][通常論文]
   

  Turfs are among the major benthic components of reef systems worldwide. The nearly complete genome sequences, basic physiological characteristics, and phylogenomic reconstruction of two phycobiliprotein-rich filamentous cyanobacteria strains isolated from turf assemblages from the Abrolhos Bank (Brazil) are investigated. Both Adonisia turfae CCMR0081(T) (= CBAS 745(T)) and CCMR0082 contain approximately 8 Mbp in genome size and experiments identified that both strains exhibit chromatic acclimation. Whereas CCMR0081(T) exhibits chromatic acclimation type 3 (CA3) regulating both phycocyanin (PC) and phycoerythrin (PE), CCMR0082 strain exhibits chromatic acclimation type 2 (CA2), in correspondence with genes encoding specific photosensors and regulators for PC and PE. Furthermore, a high number and diversity of secondary metabolite synthesis gene clusters were identified in both genomes, and they were able to grow at high temperatures (28 degrees C, with scant growth at 30 degrees C). These characteristics provide insights into their widespread distribution in reef systems.
• Bioactive significance of fucoxanthin and its effective extraction

  Kazuo Miyashita, Fumiaki Beppu, Masashi Hosokawa, Xiaoyong Liu, Shuzhou Wang

  BIOCATALYSIS AND AGRICULTURAL BIOTECHNOLOGY 26 2020年07月 [査読有り]
   

  Fucoxanthin (Fx) is a major carotenoid present in the chloroplasts of brown seaweeds and some kinds of microalgae. Because of the beneficial health effects of Fx, much attention has been focused on the considerable potential and promising applications of this compound in human health. Among the wide variety of biological activities of Fx, the interest has been mainly focused on its antiobesity effect, which is primarily based on the upregulation of thermogenesis through uncoupling protein 1 expression. Therefore, much effort has been made on the exploration for better Fx sources from different kinds of brown seaweeds and microalgae. The effective method to separate Fx has also attracted the interest of numerous researchers. Fx is conventionally extracted using organic solvents; however, solvents of petroleum origin are now strictly regulated worldwide. Thus, there is a growing demand for using greener, bio-based and renewable solvents for the extraction. From this viewpoint, edible oils may be promising green solvents. Edible oils can reduce the energy consumption in the extraction process and produce a barrier against Fx degradation. The edible oil extracts from brown seaweeds can be directly used as functional food materials containing Fx, without the need for purification.
• Preparation of Phosphatidyl-panthenol by phospholipase D-mediated transphosphatidylation and its anti-inflammatory activity on macrophage-like RAW264.7 cells

  Yukihiro Yamamoto, Kounosuke Suzuri, Tasuku Kunii, Hideyuki Kurihara, Kazuo Miyashita, Masashi Hosokawa

  BIOCATALYSIS AND AGRICULTURAL BIOTECHNOLOGY 26 101629 - 101629 2020年07月 [査読有り][通常論文]
   

  Panthenol is known to be pro-vitamin B-5 and show several functions such as wound-healing, anti-oxidative, and anti-inflammatory activities. In this study, panthenol was phosphatidylated via phospholipase D (PLD)-mediated transphosphatidylation and its anti-inflammatory effects were investigated on macrophage-like RAW264.7 cells. By PLD-mediated transphosphatidylation from phosphatidylcholine (PC), hydroxy group of p1 position in panthenol molecule was alternatively formed phosphate ester bond even though panthenol has three of hydroxy groups in the molecule. The yield was 96 mol% under optimum reaction conditions: 50 umol of PC, 1.6 U of PLD, 500 umol of panthenol, 1.6 mL/1.6 mL of ethyl acetate/0.2 M acetate buffer (pH 5.6) ratio, 10 mM of CaCl2 in the buffer, 37 degrees C for 24 h. Phosphatidyl-panthenol (P-panthenol) suppressed mRNA expression level of pro-inflammatory mediators such as IL-6, IL-1 beta, TNF-alpha and COX-2 more than precursor compounds, PC and panthenol, in activated RAW264.7 cells. P-panthenol also suppressed protein secretion levels of IL-6 and IL-1 beta in the culture medium of RAW264.7 cells. These results demonstrate that P-panthenol, which is easily synthesized in high yield, is potential compound for novel anti-inflammatory phospholipid.
• Fucoxanthin inhibits hepatic oxidative stress, inflammation, and fibrosis in diet-induced nonalcoholic steatohepatitis model mice

  Naoki Takatani, Yuka Kono, Fumiaki Beppu, Yuko Okamatsu-Ogura, Yumiko Yamano, Kazuo Miyashita, Masashi Hosokawa

  BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 528 2 305 - 310 2020年07月 [査読有り][通常論文]
   

  Nonalcoholic steatohepatitis (NASH) is associated with hepatocyte injury, excessive oxidative stress, and chronic inflammation in fatty liver, and can progress to more severe liver diseases, such as cirrhosis and hepatocellular carcinoma. However, currently there are no effective therapies for NASH. Marine carotenoid, fucoxanthin (Fx), abundant in brown seaweeds, has variable biological properties, such as anticancer, anti-inflammatory, anti-oxidative and anti-obesity. However, the effect of Fx on the development of NASH has not been explored. We investigated the protective effects of Fx in diet-induced NASH model mice fed choline-deficient L-amino acid-defined high fat diet (CDAHFD). Fx administration significantly attenuated liver weight gain and hepatic fat accumulation, resulting in the alleviation of hepatic injury. Furthermore, the Fx-fed mice, not only exhibited reduced hepatic lipid oxidation, but also decreased mRNA expression levels of inflammation and infiltration-related genes compared to that of the CDAHFD-fed mice. Moreover, fucoxanthinol and amarouciaxanthin A, two Fx metabolites exerted anti-inflammatory effects in the liver via inhibiting the chemokine production in hepatocytes. In case of fibrosis, one of the features of advanced NASH, the expression of fibrogenic factors including activatedhepatic stellate cell marker was significantly decreased in the liver of Fx-fed mice. Thus, the present study elucidated that dietary Fx not only inhibited hepatic oxidative stress and inflammation but also prevented early phase of fibrosis in the diet-induced NASH model mice. (C) 2020 Elsevier Inc. All rights reserved.
• Nutraceutical characteristics of the brown seaweed carotenoid fucoxanthin

  Kazuo Miyashita, Fumiaki Beppu, Masashi Hosokawa, Xiaoyong Liu, Shuzhou Wang

  ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS 686 108364 - 108364 2020年06月 [査読有り][通常論文]
   

  Fucoxanthin (Fx), a major carotenoid found in brown seaweed, is known to show a unique and wide variety of biological activities. Upon absorption, Fx is metabolized to fucoxanthinol and amarouciaxanthin, and these metabolites mainly accumulate in visceral white adipose tissue (WAT). As seen in other carotenoids, Fx can quench singlet oxygen and scavenge a wide range of free radicals. The antioxidant activity is related to the neuroprotective, photoprotective, and hepatoprotective effects of Fx. Fx is also reported to show anti-cancer activity through the regulation of several biomolecules and signaling pathways that are involved in either cell cycle arrest, apoptosis, or metastasis suppression. Among the biological activities of Fx, anti-obesity is the most well-studied and most promising effect. This effect is primarily based on the upregulation of thermogenesis by uncoupling protein 1 expression and the increase in the metabolic rate induced by mitochondrial activation. In addition, Fx shows anti-diabetic effects by improving insulin resistance and promoting glucose utilization in skeletal muscle.
• Fucoxanthinol attenuates oxidative stress-induced atrophy and loss in myotubes and reduces the triacylglycerol content in mature adipocytes

  Maki Yoshikawa, Masashi Hosokawa, Kazuo Miyashita, Takashi Fujita, Hoyoku Nishino, Takeshi Hashimoto

  MOLECULAR BIOLOGY REPORTS 47 4 2703 - 2711 2020年04月 [査読有り][通常論文]
   

  The combination of sarcopenia and obesity (i.e., sarcopenic obesity) is more strongly associated with disability and metabolic/cardiovascular diseases than obesity or sarcopenia alone. Therefore, countermeasures that simultaneously suppress fat gain and muscle atrophy to prevent an increase in sarcopenic obesity are warranted. The aim of this study was to investigate the simultaneous effects of fucoxanthinol (FXOH) on fat loss in mature adipocytes and the inhibition of atrophy and loss in myotubes induced by oxidative stress. C2C12 myotubes were treated with FXOH for 24 h and further incubated with hydrogen peroxide (H2O2) for 24 h. The area of myosin heavy chain-positive myotubes and the ROS concentration were measured. Mature 3T3-L1 adipocytes were treated with FXOH for 72 h. The triacylglycerol (TG) content and glycerol and fatty acid (FA) release were biochemically measured. The myotube area was smaller in H2O2-treated cells than that in control cells. However, FXOH protected against the H2O2-induced decreases in myotube area. Further, the ROS concentration was significantly higher in the FXOH-treated cells compared with that in the control cells, although it was significantly lower than that in the H2O2-treated cells. On the other hand, in the mature adipocytes, the TG content was significantly decreased by FXOH treatment compared to that in the control. Moreover, FXOH treatment significantly increased glycerol and FA release compared with that of the control. These results suggest that FXOH inhibits H2O2-induced atrophy and loss in myotubes and activates lipolysis and decreases the TG content in mature adipocytes. Accordingly, FXOH has the potential to exert anti-sarcopenic obesity effects.
• Effective extraction of carotenoids from brown seaweeds and vegetable leaves with edible oils

  Kazuyoshi Teramukai, Shusuke Kakui, Fumiaki Beppu, Masashi Hosokawa, Kazuo Miyashita

  INNOVATIVE FOOD SCIENCE & EMERGING TECHNOLOGIES 60 2020年03月 [査読有り]
   

  Factors affecting carotenoid extraction with edible oils were examined using edible brown seaweed, Sargassum horneri, as main sample. The results indicate that drying was essential to extract fucoxanthin (Fx) from S. horneri and physical (boiling) and chemical (acid/alkali) pretreatment of the wet sample increased the extraction rate of Fx. Additionally, more Fx was found from the dried S. horneri powder with a smaller particle size. The extraction rate of Fx is affected by the extraction temperature and time, showing that the effective extraction would be obtained at 50 degrees C within 12 hr extraction. Among the oils used, short-chain (C4 and C6) triacylglycerol (TAG) (SCT) and medium-chain (C8) TAG (MCT) could extract more Fx from S. horneri and more beta-carotene and lutein from spinach and olive leaves. The relatively lower viscosity of SCT and MCT would be the most likely reason for the higher extraction rates of both TAGs.
• Spirulina Lipids Alleviate Oxidative Stress and Inflammation in Mice Fed a High-Fat and High-Sucrose Diet

  Yuhong Yang, Lei Du, Masashi Hosokawa, Kazuo Miyashita

  MARINE DRUGS 18 3 2020年03月 [査読有り][通常論文]
   

  High-fat and high-sucrose diet (HFHSD)-induced obesity leads to oxidative stress and chronic inflammatory status. However, little is known about the beneficial effects of total lipids extracted from Spirulina. Hence, in the present study, Spirulina lipids were extracted with chloroform/methanol (SLC) or ethanol (SLE) and then their effects on oxidative stress and inflammation in the mice fed a HFHSD were investigated. The results show that the major lipid classes and fatty acid profiles of SLC and SLE were almost similar, but the gamma-linolenic acid (GLA) and carotenoid contents in SLE was a little higher than that in SLC. Dietary 4% SLC or SLE for 12 weeks effectively decreased the hepatic lipid hydroperoxide levels as well as increased the activities and mRNA levels of antioxidant enzymes in the mice fed a HFHSD. In addition, supplementation with SLC and SLE also markedly decreased the levels of serum pro-inflammatory cytokines and the mRNA expression of pro-inflammatory cytokines in the liver and epididymal white adipose tissue of mice fed a HFHSD, and the effects of SLC and SLE were comparable. These findings confirm for the first time that dietary Spirulina lipids could alleviate HFHSD-induced oxidative stress and inflammation.
• Preparation of n-3 Polyunsaturated Phosphatidylglycerol from Salmon Roe Lipids by Phospholipase D and In Vitro Digestion

  Liping Chen, Fumiaki Beppu, Kazuo Miyashita, Masashi Hosokawa

  EUROPEAN JOURNAL OF LIPID SCIENCE AND TECHNOLOGY 122 2 2020年02月 [査読有り]
   

  Phosphatidylglycerol (PG) is a highly functional phospholipid (PL), which has many physiological functions. However, naturally occurring PG binding n-3 polyunsaturated fatty acid (n-3 PUFA) is low in content, resulting in a scarcity of industrial bio-resources of n-3 PUFA enriched PG. The current study investigates the preparation of salmon roe PG (SRPG) from three types of salmon roe lipids and glycerol via phospholipase D (PLD)-mediated transphosphatidylation. The yields of SRPG obtained from salmon roe total lipid (SRTL) and salmon roe PL (SRPL) are higher than those obtained from purified salmon roe phosphatidylcholine (SRPC) in aqueous system. Following a 24 h reaction with 0.75 U PLD, SRTL, and SRPL yield up to 96.4 mol% and 96.7 mol% SRPG, respectively. In addition, more fatty acids are released from synthesized SRPG via hydrolysis by pancreatic enzymes than from SRPC and soybean PC in in vitro digestion model. Fatty acids at the sn-2 position of SRPG are completely liberated by 0.04 U of phospholipase A(2) (PLA(2)) during a 6 h reaction, whereas fatty acids of SRPC are partially unhydrolyzed even after a 24 h reaction. Our results suggest that SRPG converted from salmon lipids by PLD is a functional PL with high bioavailability of n-3 PUFAs. Practical Applications: Phosphatidylglycerol rich in n-3 PUFAs is prepared from salmon roe lipids (SRPG) catalyzed by PLD. The SRPG yields reach 96.4 mol% and 96.7 mol% of phosphatidylcholine contained in SRTL and SRPL, respectively, in aqueous reaction system. Fatty acids rich in n-3 PUFAs at sn-2 position of prepared SRPG are rapidly liberated by PLA(2) in an in vitro digestion model.
• Effect of Spirulina lipids on high-fat and high-sucrose diet induced obesity and hepatic lipid accumulation in C57BL/6J mice

  Yuhong Yang, Lei Du, Masashi Hosokawa, Kazuo Miyashita

  JOURNAL OF FUNCTIONAL FOODS 65 2020年02月 [査読有り][通常論文]
   

  Obesity is characterized by abnormal or excessive fat accumulation that impairs health. In this study, the effects of Spirulina lipids (SL) and fish oil (FO) on obesity and hepatic lipid accumulation in high-fat and high-sucrose diet induced obese C57BL/6J mice were evaluated and compared. After 12 weeks of feeding, 4% gamma-linolenic acid-enriched SL supplementation effectively reduced the gain of body weight, total white adipose tissue (WAT) weight and hepatic lipid levels in obese mice. Although dietary 4% FO also tended to suppress the increases of body weight and WAT weight in mice, no statistical difference was observed. The suppression of hepatic lipid accumulation by SL should be through regulating sterol regulatory element binding protein-1c (SREBP-1c), SREBP-2-mediated triacylglycerol and cholesterol synthesis pathway as well as via enhancement of peroxisome proliferator-activated receptor alpha (PPAR alpha)-mediated beta-oxidation. These findings firstly confirmed that SL could alleviate diet-induced obesity and hepatic lipid accumulation.
• 海洋性カロテノイドの健康機能性に関する最近の動向

  高谷 直己, 細川 雅史

  日本食品安全協会会誌 15 78 - 85 2020年 [査読無し]
  
• Total Lipids Content, Lipid Class and Fatty Acid Composition of Ten Species of Microalgae

  Yuhong Yang, Lei Du, Masashi Hosokawa, Kazuo Miyashita

  JOURNAL OF OLEO SCIENCE 69 10 1181 - 1189 2020年 [査読有り]
   

  Microalgae is a potential producer of functional lipids such as n-3 polyunsaturated fatty acids (PUFA) and fucoxanthin. In the present study, lipids from ten microalgae species were analyzed especially focusing on the fucoxanthin, lipid and fatty acid compositions. The study revealed a remarkable variation in total lipids content, fucoxanthin content, lipid class composition and n-3 PUFA content in individual species, although they belong to the same genus. Among microalgac examined, Pavlova lutheri contained the highest total lipids content (313.59 mg g(-1) dry weight) and considerable amount of fucoxanthin (3.13 mg g(-1) dry weight). It also had the highest level (28.01%) of total n-3 PUFA with high level of eicosapentaenoic acid (EPA) (17.76%) and docosahexaenoic acid (DHA) (7.61%). The highest fucoxanthin content (5.19 mg g(-1) dry weight) was observed in Chaetoceros gracilis. C gracilis also contained relatively high level of total lipids (228.87 mg g(-1). dry weight) and 10.67% EPA. The results also demonstrated that Nannochloropsis oculata contained the greatest amount of EPA (26.21%), while Isochrysis galbana had the highest level of DHA (8.76%). And both microalgae contained 1.71 and 4.44 mg g(-1) dry weight fucoxanthin, respectively. Microalgal lipids containing abundant fucoxanthin and n-3 PUFA such as EPA and DHA in the present study will be used as nutraceutical lipids with great commercial potential.
• The Effect of n-3 PUFA Binding Phosphatidylglycerol on Metabolic Syndrome-Related Parameters and n-3 PUFA Accretion in Diabetic/Obese KK-A(y) Mice

  Liping Chen, Naoki Takatani, Fumiaki Beppu, Kazuo Miyashita, Masashi Hosokawa

  NUTRIENTS 11 12 2019年12月 [査読有り][通常論文]
   

  n-3 Polyunsaturated fatty acid binding phospholipids (n-3 PUFA-PLs) are known to be potent carriers of n-3 PUFAs and provide health benefits. We previously prepared n-3 PUFA binding phosphatidylglycerol (n-3 PUFA-PG) by phospholipase D-mediated transphosphatidylation. Because PG has excellent emulsifiability, n-3 PUFA-PG is expected to work as a functional molecule with properties of both PG and n-3 PUFAs. In the present study, the health benefits and tissue accretion of dietary n-3 PUFA-PG were examined in diabetic/obese KK-A(y) mice. After a feeding duration over 30 days, n-3 PUFA-PG significantly reduced the total and non-HDL cholesterols in the serum of diabetic/obese KK-A(y) mice. In the mice fed n-3 PUFA-PG, but not n-3 PUFA-TAG, hepatic lipid content was markedly alleviated depending on the neutral lipid reduction compared with the SoyPC-fed mice. Further, the n-3 PUFA-PG diet increased eicosapentaenoic acid and docosahexaenoic acid (DHA) and reduced arachidonic acid in the small intestine, liver, perirenal white adipose tissue, and brain, and the ratio of the n-6 PUFAs to n-3 PUFAs in those tissues became lower compared to the SoyPC-fed mice. Especially, the DHA level was more significantly elevated in the brains of n-3 PUFA-PG-fed mice compared to the SoyPC-fed mice, whereas n-3 PUFA-TAG did not significantly alter DHA in the brain. The present results indicate that n-3 PUFA-PG is a functional lipid for reducing serum and liver lipids and is able to supply n-3 PUFAs to KK-A(y) mice.
• Variation in Lipid Components from 15 Species of Tropical and Temperate Seaweeds

  Eko Susanto, A. Suhaeli Fahmi, Masashi Hosokawa, Kazuo Miyashita

  MARINE DRUGS 17 11 2019年11月 [査読有り][通常論文]
   

  The present study describes the variation in lipid components from 15 species of seaweeds belonging to the Chlorophyta, Ochrophyta, and Rhodophyta phyla collected in tropical (Indonesia) and temperate (Japan) areas. Analyses were performed of multiple components, including chlorophylls, carotenoids, n-3 and n-6 polyunsaturated fatty acids (PUFAs), and alpha tocopherol (alpha-Toc). Chlorophyll (Chl) and carotenoid contents varied among phyla, but not with the sampling location. Chl a and b were the major chlorophylls in Chlorophyta. Chl a and Chl c were the main chlorophylls in Ochrophyta, while Chl a was the dominant chlorophylls in Rhodophyta. beta-Carotene and fucoxanthin were detected as major seaweed carotenoids. The former was present in all species in a variety of ranges, while the latter was mainly found in Ochrophyta and in small quantities in Rhodophyta, but not in Chlorophyta. The total lipids (TL) content and fatty acids composition were strongly affected by sampling location. The TL and n-3 PUFAs levels tended to be higher in temperate seaweeds compared with those in tropical seaweeds. The major n-3 PUFAs in different phyla, namely, eicosapentaenoic acid (EPA) and stearidonic acid (SDA) in Ochrophyta, alpha-linolenic acid (ALA) and SDA in Chlorophyta, and EPA in Rhodophyta, accumulated in temperate seaweeds. Chlorophylls, their derivatives, and carotenoids are known to have health benefits, such as antioxidant activities, while n-3 PUFAs are known to be essential nutrients that positively influence human nutrition and health. Therefore, seaweed lipids could be used as a source of ingredients with health benefits for functional foods and nutraceuticals.
• Phospholipase A 2 -Mediated preparation of phosphatidylcholine containing ricinoleic acid and its anti-inflammatory effect on murine macrophage-like RAW264.7 cells

  Yukihiro Yamamoto, Kazuki Harada, Suzuna Kasuga, Masashi Hosokawa

  Biocatalysis and Agricultural Biotechnology 19 2019年05月01日 

  Ricinoleic acid (RA) is a type of fatty acid found in castor oil and has been known to have anti-inflammatory effects. Phospholipids are useful functional compounds in food/medical fields due to their amphiphilic property and biocompatibility. The purpose of this study was to prepare phospholipid (PL) containing RA and to evaluate the anti-inflammatory activity of a prepared PL in vitro. Lyso-phosphatidylcholine (LPC) from egg yolk was subjected to phospholipase A 2 -mediated esterification for the preparation of phosphatidylcholine containing RA at sn-2 position (2-RA-PC). The prepared 2-RA-PC was then evaluated for its anti-inflammatory activity against the murine macrophage-like cell line RAW264.7 stimulated by lipopolysaccharide. Using glycerol as solvent and formamide as water mimic, 2-RA-PC was successfully prepared. Upon optimizing the molar ratio (RA/LPC), the amount of glycerol, and the reaction time, a maximum yield of 57.5 mol% was obtained. Analysis of fatty acid compositions of substrate LPC, RA, and synthesized PC suggested almost all RA was incorporated into sn-2 position of LPC. Down regulation of mRNA expression of pro-inflammatory cytokines, interleukin 6 and 1β was higher for 2-RA-PC than for RA or Soy-PC, which suggests that the anti-inflammatory effects of RA were improved following phosphatidylation. Our data suggest that 2-RA-PC is a potential lipid for use as an anti-inflammatory compound.
• Carotenoid Profiling of a Red Seaweed Pyropia yezoensis: Insights into Biosynthetic Pathways in the Order Bangiales

  Jiro Koizumi, Naoki Takatani, Noritoki Kobayashi, Koji Mikami, Kazuo Miyashita, Yumiko Yamano, Akimori Wada, Takashi Maoka, Masashi Hosokawa

  MARINE DRUGS 16 11 2018年11月 [査読有り][通常論文]
   

  Carotenoids are natural pigments that contribute to light harvesting and photo-protection in photosynthetic organisms. In this study, we analyzed the carotenoid profiles, including mono-hydroxy and epoxy-carotenoids, in the economically valuable red seaweed Pyropia yezoensis, to clarify the detailed biosynthetic and metabolic pathways in the order Bangiales. P. yezoensis contained lutein, zeaxanthin, -carotene, and -carotene, as major carotenoids in both the thallus and conchocelis stages. Monohydroxy intermediate carotenoids for the synthesis of lutein with an epsilon-ring from -carotene, -cryptoxanthin (,epsilon-caroten-3'-ol), and zeinoxanthin (,epsilon-caroten-3-ol) were identified. In addition, -cryptoxanthin, an intermediate in zeaxanthin synthesis from -carotene, was also detected. We also identified lutein-5,6-epoxide and antheraxanthin, which are metabolic products of epoxy conversion from lutein and zeaxanthin, respectively, by LC-MS and H-1-NMR. This is the first report of monohydroxy-carotenoids with an epsilon-ring and 5,6-epoxy-carotenoids in Bangiales. These results provide new insights into the biosynthetic and metabolic pathways of carotenoids in red seaweeds.
• Consumption of the edible sea urchin Mesocentrotus nudus attenuates body weight gain and hepatic lipid accumulation in mice

  Ryoko Yamamoto, Hisanori Minami, Hiromi Matsusaki, Mami Sakashita, Naoki Morita, Osamu Nishimiya, Naonobu Tsutsumi, Masashi Hosokawa, Yutaka Itabashi, Toshiro Matsui, Kazuhiro Urad

  JOURNAL OF FUNCTIONAL FOODS 47 40 - 47 2018年08月 [査読有り]
   

  The beneficial health effects of edible sea urchin consumption in mice fed a normal (ND) or high-fat diet (HFD) were investigated in this study. Notably, sea urchin-administered (250, 500, 1000 mg/kg) mice exhibited lower body, liver, and visceral fat weights, lower plasma levels of aspartate aminotransferase and alanine aminotransferase, and lower hepatic triacylglycerol levels than those fed carboxymethyl cellulose (CMC). Despite the high levels of cholesterol found in sea urchins, intake of these organisms had no effect on plasma cholesterol levels among the mice tested. Additionally, sea urchin consumption resulted in enhanced levels of arachidonic acid and docosahexaenoic acid within mouse livers. Lastly, mice fed HFD with sea urchin (500 mg/kg) exhibited increased mRNA expression of uncoupling protein-1 within brown adipose tissue, compared with those fed HFD with CMC. In conclusion, consumption of sea urchin might provide a protective effect against the development of obesity and/or nonalcoholic fatty liver disease.
• Detection and identification of furan fatty acids from fish lipids by high-performance liquid chromatography coupled to electrospray ionization quadrupole time-of-flight mass spectrometry

  Hajime Uchida, Yutaka Itabashi, Ryuichi Watanabe, Ryoji Matsushima, Hiroshi Oikawa, Toshiyuki Suzuki, Masashi Hosokawa, Naonobu Tsutsumi, Kazuhiro Ura, Donato Romanazzi, Matthew R. Miller

  FOOD CHEMISTRY 252 84 - 91 2018年06月 [査読有り][通常論文]
   

  Using high-performance liquid chromatography coupled to high-resolution electrospray ionization quadrupole time-of-flight mass spectrometry (HPLC/ESI-Q-TOF-MS), we have developed a new method for detection and identification of furan fatty acids (F-acids), which are widely distributed in living organisms and foods as minor lipid components and are known to have antioxidant and anti-inflammatory effects. For this purpose, total fatty acids prepared from the testis lipids of Japanese chum salmon (Oncorhynchus keta) were examined without any concentration or isolation of F-acids. In negative ESI mode, F-acids gave a prominent [M-H]-ion, by which individual F-acids could be detected and identified. High-resolution extracted ion chromatograms clearly showed the occurrence of five major F-acid homologs as already reported by GC/MS. The method was successfully applied to several fish samples and revealed the occurrence of F-acids for the first time in the two New Zealand fish, hoki (Macruronus novaezelandiae) and school shark (Galeorhinus galeus).
• Acrolein as a Major Volatile in the Early Stages of Fish Oil TAG Oxidation

  Ako Shibata, Mariko Uemura, Masashi Hosokawa, Kazuo Miyashita

  JOURNAL OF OLEO SCIENCE 67 5 515 - 524 2018年05月 [査読有り][通常論文]
   

  Fish oil rich in docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) is known to have an unpleasant smell, even at low oxidation levels. Therefore, it is highly important to know the major volatiles formed during the early stages of fish oil oxidation. Comparative study with solid-phase microextraction (SPME) and static headspace (SHS) methods showed that 2-propenal (acrolein) was formed as the major volatile from the beginning of fish oil triacylglycerol (TAG) oxidation. The effectiveness of SPME extraction on each volatile was different from each fiber. Among the three different SPME fibers used in the present study, carboxen/polydimethylsiloxane (CAR/PDMS) was determined to be a better fiber for measuring the volatiles, including acrolein. The present study also showed that the non-selective SHS method is useful for determining the characteristic volatile formation in the early stages of fish oil TAG oxidation.
• Comparison of oxidative stability of monogalactosyl diacylglycerol, digalactosyl diacylglycerol, and triacylglycerol containing polyunsaturated fatty acids.

  Hazahari, N.Y, B, Hosokawa, M, Miyashita, K

  Food Nutr. Sci. 9 221 - 234 2018年 [査読有り][通常論文]
  
• Health impact of marine carotenoids.

  Miyashita, K, Hosokawa, M

  J. Food Bioact. 1 34 - 40 2018年 [査読有り][通常論文]
  
• 高度不飽和脂肪酸に対するスフィンゴイド塩基とα-トコフェロールの相乗的抗酸化効果

  宮下和夫, 上村麻梨子, 細川雅史

  オレオサイエンス 18 317 - 324 2018年 [査読有り][通常論文]
  
• Effective Prevention of Oxidative Deterioration of Fish Oil: Focus on Flavor Deterioration

  Kazuo Miyashita, Mariko Uemura, Masashi Hosokawa

  ANNUAL REVIEW OF FOOD SCIENCE AND TECHNOLOGY, VOL 9 9 209 - 226 2018年 [査読有り][通常論文]
   

  Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), both abundant in fish oil, are known to have significant biochemical and physiological effects primarily linked to the improvement of human health, especially cardiovascular and brain health. However, the incorporation of fish oil into foods and beverages is often challenging, as fish oil is very easily oxidized and can cause undesirable flavors. This review discusses this rapid formation of the fishy and metallic off-flavors, focusing especially on an early stage of fish oil oxidation. Although oxidative stability and quality of commercialized fish oil have improved over the past few years, there is a still a problem with its application: Flavor deterioration can be found even at very low oxidation levels. This review also notes the effective way to inhibit the formation of the volatile compounds responsible for the flavor deterioration.
• Spatial and seasonal variations in the biofunctional lipid substances (fucoxanthin and fucosterol) of the laboratory-grown edible Japanese seaweed (Sargassum horneri Turner) cultured in the open sea

  Masaru Terasaki, Chikara Kawagoe, Atsushi Ito, Hiroko Kumon, Bhaskar Narayan, Masashi Hosokawa, Kazuo Miyashita

  SAUDI JOURNAL OF BIOLOGICAL SCIENCES 24 7 1475 - 1482 2017年11月 [査読有り][通常論文]
   

  This work studied the effect of spatial and seasonal differences on the accumulation of functional lipid components in Sargassum horneri (Turner), an edible Japanese seaweed popularly called Akamoku. S. horneri obtained from Samenoura bay area of Japan was laboratory cultured to evaluate the effect of temperature on the accumulation of total lipids (TL), fucoxanthin (Fx) and fucosterol (Fs) by the alga. The laboratory cultured 3 month old S. horneri were cultured in the open sea in two different geographical locations off Usujiri and Matsushima to evaluate the monthly variations, over a year, in their TL, Fx and Fs contents. S. horneri grown off the Usujiri area accumulated the maximum TL close to 193 mg g(-1) dry weight during the coldest part of the year. Fx and Fs contributed 5.6% and 16.2% of the TL in S. horneri harvested off Usujiri in February. Further, in spite of being the same species and parent stock, S. horneri grown off the Matsushima area accumulated less TL, Fx and Fs as compared to their Usujiri counterparts. Our study clearly indicates the role of temperature and light apart from nutritional profile and depth of waters where the seaweed was grown on the accumulation of functional lipid components in S. horneri. (C) 2016 The Authors. Production and hosting by Elsevier B.V. on behalf of King Saud University.
• Docosapentaenoic Acid (22:5n-3) Downregulates mRNA Expression of Pro-inflammatory Factors in LPS-activated Murine Macrophage Like RAW264.7 Cells

  Yanzhu Tian, Ami Katsuki, Donato Romanazzi, Matthew R. Miller, Serean L. Adams, Kazuo Miyashita, Masashi Hosokawa

  JOURNAL OF OLEO SCIENCE 66 10 1149 - 1156 2017年10月 [査読有り][通常論文]
   

  Docosapentaenoic acid (22:5n-3, n-3 DPA) is a n-3 polyunsaturated fatty acid (PUFA) found in fish oil, and has been reported to have health benefits. This study investigated conversion of n-3 DPA, and examined the anti-inflammatory effects of n-3 DPA on activated macrophages. Murine macrophage-like RAW264.7 cells were incubated in culture media containing n-3 DPA for 72 h. The level of n-3 DPA in the fatty acid composition of the total lipid fraction increased in a dose-dependent manner. Furthermore, the levels of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) were higher in treated cells than in control cells. In RAW264.7 cells stimulated by lipopolysaccharide (LPS), n-3 DPA significantly down regulated mRNA expression of pro-inflammatory factors such as IL-6, IL-1 beta, iNOS and COX-2. Production of IL-6 was also reduced by n-3 DPA in a dose-dependent manner. We found that n-3 DPA treatment resulted in greater IL-6 mRNA down-regulation than that achieved with EPA treatment, and was similar to that of DHA treatment. Furthermore, expression levels of IL-6 and IL-1 beta mRNAs were measured in the presence of the delta-6 desaturase inhibitor SC26196 in the culture medium to inhibit the conversion of n-3 DPA to DHA. There was no significant difference in the down-regulation in the mRNA expression of pro inflammatory cytokines in RAW264.7 cells by n-3 DPA with or without presence of SC26196. These results demonstrate that n-3 DPA exhibits anti-inflammatory effects in activated RAW264.7 cells, which are independent of DHA conversion.
• Fatty Acid and Lipid Class Composition of the Microalga Phaeodactylum tricornutum

  Yu-Hong Yang, Lei Du, Masashi Hosokawa, Kazuo Miyashita, Yume Kokubun, Hisayoshi Arai, Hiroyuki Taroda

  JOURNAL OF OLEO SCIENCE 66 4 363 - 368 2017年04月 [査読有り][通常論文]
   

  n-3 Polyunsaturated fatty acids (PUFAs) are essential for the prevention and/or risk reduction of some diseases, including cardiovascular diseases and cancer. Therefore, PUFAs-rich marine microalgae have received considerable research attention. The diatom Phaeodactylum tricornutum, a rich source of lipids and fucoxanthin, has commercial applications in the food and pharmaceutical industries. In this study, the lipid class composition and fatty acid distribution in P. tricornutum under high-density and scaleup cultivation were investigated by thin-layer chromatography and gas chromatography. The fucoxanthin content was quantified by reverse-phase high-performance liquid chromatography. Both total lipid and fucoxanthin contents were high, accounting for 321.89 and 4.47 mg/g dry weight, respectively. Neutral lipids were the major lipids, and triacylglycerol was the predominant neutral lipids (33.63% of total lipids). The glycolipids (GLs) and phospholipids (PLs) represented 20.95% and 31.39% of total lipids, respectively. Sulfoquinovosyl diacylglycerol (SQDG) was the largest GLs fraction (9.81% of total lipids). Phosphatidylglycerol (PG) was the major PLs and accounted for 13.53% of total lipids. The main fatty acids were hexadecanoic acid (C16:0), palmitoleic acid (C16:1), and eicosapentaenoic acid. In addition, docosahexaenoic acid only accumulated in the PLs fraction. These findings provide new information on the lipid types, fatty acid composition of each lipid class, and the fucoxanthin content in P tricornutum.
• Reduction of HbA1c levels by fucoxanthin-enriched akamoku oil possibly involves the thrifty allele of uncoupling protein 1 (UCP1): a randomised controlled trial in normal-weight and obese Japanese adults

  Nana Mikami, Masashi Hosokawa, Kazuo Miyashita, Hitoshi Sohma, Yoichi M. Ito, Yasuo Kokai

  JOURNAL OF NUTRITIONAL SCIENCE 6 e5  2017年02月 [査読有り][通常論文]
   

  Lifestyle-related problems are becoming a major health threat in East Asian countries. Therefore, finding an efficacious nutraceutical for this population is important. One candidate is fucoxanthin (Fx), a carotenoid abundantly found in edible brown seaweed that has been associated with a number of valuable health-promoting benefits. Unfortunately, clinical studies of Fx are limited. In the present study, we aimed to evaluate the effects of Fx on obesity-related parameters in Japanese subjects harbouring an SNP associated with lifestyle-related problems. In all, sixty normal-weight and obese Japanese adults with BMI over 22 kg/m(2) were single-blinded and randomly assigned to three Fx-dose cohorts and administered Fx-enriched akamoku oil containing Fx at 0, 1 or 2 mg/d for 8 weeks (n 20 per group). Parameters relating to obesity and serum Fx metabolites were measured before and after intervention, but no significant differences were observed between and within the groups. Despite no changes in visceral fat areas and resting energy expenditures after intervention, we observed a significant decline in HbA1c levels in the 2 mg/d Fx group compared with that in the 0 mg/d group (P < 0.05), which was correlated with an increase in serum fucoxanthinol (Fx metabolite) levels. In addition, HbA1c levels declined more significantly in subjects with G/G alleles of the uncoupling protein 1 (UCP1) gene than in those with the A/A and A/G alleles (P < 0.05). We conclude that although Fx supplementation does not affect visceral fat areas, it may reduce HbA1c levels in those harbouring the thrifty allele of UCP1-3826A/G.
• Squalene modulates fatty acid metabolism: Enhanced EPA/DHA in obese/diabetic mice (KK-A(y)) model

  Sangeetha Ravi Kumar, Ippei Yamauchi, Bhaskar Narayan, Ami Katsuki, Masashi Hosokawa, Kazuo Miyashita

  EUROPEAN JOURNAL OF LIPID SCIENCE AND TECHNOLOGY 118 12 1935 - 1941 2016年12月 [査読有り][通常論文]
   

  Biosynthesis of long-chain n-3 fatty acids from precursors is limited. In vivo effect of squalene (SQ) on the metabolic fate of n-3 fatty acid precursors in obese/diabetic KK-A(y) rodent model was evaluated in our work. Soybean oil, being rich in ALA (18:3 n-3; a known precursor of EPA/DHA), was chosen as the n-3 fatty acid precursor rich source. A high-fat diet (20%) containing 7% soybean oil (SO) was fed to obesity/diabetes-prone male KK-A(y) mice (control). In the case of diets fed to test groups, soybean oil was replaced with 5% SO and 2% SQ. Hepatic DHA levels increased (four fold) in SQ fed group over control (p<0.05). Gene and protein expressions of (5) and (6) desaturases, key enzymes involved in the fatty acid metabolism, further supported the results. Also, SQ exhibited a hypotriglyceridemic and hypoglycemic effect. The results clearly indicated the effect of SQ in modulating the n-3 fatty acid metabolism, including EPA/DHA synthesis in the presence of n-3 fatty acid precursor. This is the first report of enhancement of in vivo DHA/EPA by SQ and in turn, modulating the physiological fatty acid profile. Practical applications: Squalene (SQ) is an important marine biofunctional material that is found in some terrestrial sources as well. Squalene, being a cholesterol precursor, forms an interesting subject of research for its effect in vivo. SQ significantly enhanced proportions of EPA and/or DHA when their n-3 fatty acid precursors were available in the diet. The study further establishes the usefulness of SQ in functional food formulations. The work provides an important basis for further evaluation of the role of SQ in normal and disease conditions.KK-A(y) mice were fed high fat/sucrose diet to induce obesity/diabetes. Fat source in control diet was lard and soybean oil while experimental group diet contained 2% squalene+13% lard+5% soybean oil. Feeding squalene for 4weeks modulated fatty acid metabolism with increased docosahexaenoic acid (DHA) and decrease in triglycerides (TG), compared to control. The enhanced DHA in the fatty acid profile was supported by upregulated mRNA expression of (5)-desaturase enzyme and protein expression of (5) and (6) desaturases (FADS1 and FADS2). Additionally, squalene had a hypoglycemic effect in the mice.
• Bioconversion of Docosapentaenoic Acid in Human Cell Lines, Caco-2, HepG2, and THP-1

  Yanzhu Tian, Donato Romanazzi, Kazuo Miyashita, Masashi Hosokawa

  JOURNAL OF OLEO SCIENCE 65 12 1017 - 1022 2016年12月 [査読有り][通常論文]
   

  Docosapentaenoic acids (DPAs) are long chain polyunsaturated fatty acids that exist as two major structural isomers: n-3 DPA and n-6 DPA. n-3 DPA is found in seal meat, salmon and abalone, and n-6 DPA is found in several marine microbial oil. We investigated the bioconversion of n-3 and n-6 DPAs in three different human cell lines, Caco-2, HepG2, and THP-1. n-3 DPA was converted to docosahexaenoic acid only in HepG2 cells. In contrast, retro-conversion to eicosapentaenoic acid (EPA) was observed in all three cell lines. n-6 DPA was also retro-converted to arachidonic acid (AA) in Caco-2 and HepG2 cells. EPA and AA were particularly elevated in Caco-2 cells, compared to HepG2 cells. Further, the retro-conversion of n-3 DPA led to a greater increase of EPA in the phospholipid fraction than in the neutral lipid fraction.
• Inhibitory Effect of Dihydrosphingosine with α-Tocopherol on Volatile Formation during the Autoxidation of Polyunsaturated Triacylglycerols.

  Uemura M, Shibata A, Hosokawa M, Iwashima-Suzuki A, Shiota M, Miyashita K

  Journal of oleo science 65 9 713 - 722 2016年09月 [査読有り][通常論文]
   

  The effect of dihydrosphingosine (d18:0) on triacylglycerol (TAG) oxidation was examined with and without alpha-tocopherol. Three types of TAG from fish, linseed, and soybean oil were oxidized at 50 degrees C to determine the effect of dihydrosphingosine (d18:0) with or without alpha-tocopherol on triacylglycerol (TAG) oxidation. The analysis of oxygen consumption and total volatile formation demonstrated a small effect of d18:0 on TAG oxidation in the absence of alpha-tocopherol. On the other hand, the combination of d18:0 with alpha-tocopherol showed strong antioxidant activity and completely inhibited volatile formation within 1400 h for soybean oil TAG, 650 h for linseed oil TAG, and 380 h for fish oil TAG.
• Combined effect of astaxanthin and squalene on oxidative stress in vivo

  Sangeetha Ravi Kumar, Bhaskar Narayan, Yuki Sawada, Masashi Hosokawa, Kazuo Miyashita

  MOLECULAR AND CELLULAR BIOCHEMISTRY 417 1-2 57 - 65 2016年06月 [査読有り][通常論文]
   

  Obesity and diabetes, risk factors for metabolic syndrome, are characterized by oxidative stress and inflammatory responses. Marine biofunctionals, astaxanthin (Ax) and squalene (SQ), were evaluated for their combined effect. Groups of male KK-A (y) mice were fed high fat/sucrose diet for 4 weeks, supplemented with either 0.1 %Ax, 2 %SQ or 0.1 %Ax + 2 %SQ. In comparison to control, Sod was elevated in only Ax + SQ. However, Gpx was highest in Ax + SQ, indicating the combined antioxidant effect of Ax and SQ. This was supported by elevated mRNA expression of Sod1 and Gpx1. Except adiponectin (elevated in Ax and Ax + SQ), expression of other inflammatory markers was not altered. Blood glucose levels were decreased in SQ and Ax + SQ while liver triglycerides decreased in SQ group. This is the first in vivo study demonstrating combined effects of Ax and SQ resulting in antioxidant effects and modulation of glucose/triglyceride levels. This study highlights the benefit of utilizing Ax and SQ together for management of obesity/diabetes.
• Does squalene alter the antioxidant potential of astaxanthin and fucoxanthinol? In vitro evidence in RAW 264.7 cells, a murine macrophage

  Sangeetha Ravi Kumar, Bhaskar Narayan, Yuki Kizawa, Masashi Hosokawa, Kazuo Miyashita

  JOURNAL OF FOOD SCIENCE AND TECHNOLOGY-MYSORE 53 4 2139 - 2143 2016年04月 [査読有り][通常論文]
   

  Astaxanthin (Ax) and fucoxanthin/fucoxanthinol (FuOH) are marine xanthophylls exhibiting anti-oxidant effects. Squalene (SQ) is a triterpenoid and is a precursor of sterols. This study aimed to determine if SQ can improve the effect of Ax/FuOH on lipid peroxidation. RAW 264.7 cells were treated with different concentrations of Ax, FuOH and SQ and corresponding rate of cell survival was noted. In addition,combination groups - Ax + SQ and FuOH + SQ- were also run. Cells treated with Ax, FuOH, SQ, Ax + SQ and FuOH + SQ were stimulated with lipopolysaccharide and lipid hydroperoxides were estimated. Results showed that 5 mu M Ax, 2 mu M FuOH and 10 mu M SQ supported cell survival. In presence of SQ, cell viability improved for higher concentrations of FuOH (5, 10 mu M). Lipid hydroperoxides were supressed by Ax, FuOH, Ax + SQ and FUOH +SQ and were significantly lower in Ax + SQ, indicating the synergistic effect of Ax and SQ. To conclude, combination of Ax with SQ enhances its ability to supress lipid peroxidation while with FuOH, SQ attenuates the toxic effect at higher doses. Moreover, this is the first time that the combined effect of SQ and carotenoids has been studied and reported.
• Lipids, Fatty Acids, and Fucoxanthin Content from Temperate and Tropical Brown Seaweeds

  Eko Susanto, Akhmad Suhaeli Fahmi, Masayuki Abe, Masashi Hosokawa, Kazuo Miyashita

  2ND INTERNATIONAL SYMPOSIUM ON AQUATIC PRODUCTS PROCESSING AND HEALTH, ISAPPROSH 2015 7 66 - 75 2016年 [査読有り][通常論文]
   

  Brown seaweeds lipid fraction contains several bioactive components such as Fx, polyphenol and n-3 PUFA. In this research, total lipids, Fx and FA compositions of brown seaweeds harvested from cold waters and warm waters were evaluated. The seven brown seaweeds studied were collected in different months from two different geographical areas, viz. cold waters (Japan) and warm waters (Indonesia). The result show that total lipid and Fucoxanthin in temperate brown seaweeds were higher than tropical brown seaweeds. The major PUFA from warm water seaweeds were 16: 0, 18: 1n-9, 20: 4n-6, and cold water continued dominantly 16: 0, 20: 4n-6, 20: 5n-3. Temperate brown seaweeds [S. horneri (Turner) J. Agardh] was rich in fucoxanthin and n-3 PUFA especially EPA. (C) 2016 The Authors. Published by Elsevier B.V.
• A protocol for human serum fucoxanthinol quantitation using LC-MS/MS system.

  Mikami, N, Hosokawa, M, Abe, M, Miyashita, K, Sohma, H, Kokai, Y

  J. Nutri. Med. Diet. Care. 2 019  2016年 [査読有り][通常論文]
  
• The dietary effect of milk sphingomyelin on the lipid metabolism of obese/diabetic KK-A(y) mice and wild-type C57BL/6J mice

  Ippei Yamauchi, Mariko Uemura, Masashi Hosokawa, Ai Iwashima-Suzuki, Makoto Shiota, Kazuo Miyashita

  FOOD & FUNCTION 7 9 3854 - 3867 2016年 [査読有り][通常論文]
   

  Purified milk sphingomyelin (SM) was obtained from lipid concentrated butter serum (LC-BS) by successive separations involving solvent fractionation, selective saponification, and silicic acid column chromatography. The SM obtained was given to obese/diabetic KK-A(y) mice and wild-type C57BL/6J mice. SM supplementation significantly increased fecal lipids paralleled with a decrease in non-HDL cholesterol levels in the serum and neutral lipids and in cholesterol levels in the livers of KK-A(y) mice. The reduction of liver lipid levels also resulted in a decrease in the total fatty acid content of the KK-A(y) mice livers, while n-3 fatty acids derived from the conversion of a-linolenic acid (18:3n-3) increased due to SM supplementation. In contrast to the KK-A(y) mice, little change in the serum and liver lipids was observed in wild-type C57BL/6J mice. The present study suggests that SM may be effective only in subjects with metabolic disorders.
• Dietary ALA from Spinach Enhances Liver n-3 Fatty Acid Content to Greater Extent than Linseed Oil in Mice Fed Equivalent Amounts of ALA

  Miho Kuroe, Hiroyuki Kamogawa, Masashi Hosokawa, Kazuo Miyashita

  LIPIDS 51 1 39 - 48 2016年01月 [査読有り][通常論文]
   

  Although several works have reported absorption rate differences of n-3 polyunsaturated fatty acids (PUFA) bound to different lipid forms, such as ethyl ester, triacylglycerol (TAG), and phospholipids, no studies have investigated the effect of n-3 PUFA from glycolipids (GL). The present study compared the fatty acid contents of tissue and serum lipids from normal C57BL/6J mice fed two types of alpha-linolenic acid (ALA)-rich lipids, spinach lipid (SPL), and linseed oil (LO). ALA was primarily present as the GL form in SPL, while it existed as TAG in LO. Supplementation of both lipids increased ALA and its n-3 metabolites, eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid, and decreased n-6 PUFA, linoleic acid and arachidonic acid, in the livers, small intestines, and sera of the treated mice compared with those of the control group. When the comparison between the SPL and LO diets containing the same amount of ALA was conducted, the EPA and DPA levels in the liver lipids from mice fed the SPL diet were significantly higher than those fed the LO diet. Additionally, the total contents of n-3 PUFA of lipids from the livers, small intestines, and sera of the SPL group were higher than those of the LO group.
• Formation of Acrolein in the Autoxidation of Triacylglycerols with Different Fatty Acid Compositions

  Ako Shibata, Mariko Uemura, Masashi Hosokawa, Kazuo Miyashita

  JOURNAL OF THE AMERICAN OIL CHEMISTS SOCIETY 92 11-12 1661 - 1670 2015年12月 [査読有り][通常論文]
   

  Fish, echium, linseed, and soybean oil triacyglycerols (TAGs) were oxidized at 50 or 60 A degrees C to determine the effect of the polyunsaturated fatty acid composition on the volatile product formation. The analysis of the oxygen consumption and total volatile formation demonstrated that the soybean oil TAG had the highest oxidative stability followed by linseed, echium, and fish oil TAGs. Our results were in agreement with the expected average number of bis-allylic positions of each TAG. Higher quantities of acrolein (2-propenal) and propanal were detected using the static headspace gas chromatography method at the early stages of oxidation of echium and fish oil TAGs; however, a considerable amount of propanal and only a small amount of acrolein were found in the oxidized linseed oil TAG. The peak area ratios of acrolein to propanal were 0.115, 0.569, and 2.554 after the 8-h oxidation of linseed, echium, and fish oil TAG, respectively, suggesting the preferential formation of acrolein, especially during the fish oil TAG oxidation. The acrolein quickly increased during the first stage of oxidation, but thereafter it either did not change or slightly decreased during the fish oil oxidation. Because fish oil induces flavor deterioration from the very early stage of the oxidation, the acrolein formation observed in the present study may be important for fish oil deterioration.
• The Beneficial Health Effects of Fucoxanthin

  Kazuo Miyashita, Masashi Hosokawa

  Genomics, Proteomics and Metabolomics in Nutraceuticals and Functional Foods: Second Edition 122 - 134 2015年10月05日 [査読無し][通常論文]
   

  The beneficial effects of carotenoids on human health are thought to come from their antioxidant properties. However, there are other physiological activities that carotenoids have that may play a larger role in influencing human health. The beneficial effect of fucoxanthin supplementation on improving metabolic disorders such as hyperglycemia is due largely to its regulatory effect on gene and protein expression rather than the ability of fucoxanthin to scavenge active oxygen species and/or free radicals. Fucoxanthin inhibits cancer cell growth more effectively than other carotenoids by arresting the cell cycle and triggering apoptosis. The higher activity of fucoxanthin is related to the allenic bond of its chemical structure. This unique structure is responsible for the anti-obesity effect based on the specific molecular mechanism that has not been found in other carotenoids. Nutrigenomic studies reveal that fucoxanthin induces uncoupling protein 1 (UCP1) expression in abdominal white adipose tissue (WAT) mitochondria that leads to the oxidation of fatty acids and heat production in the WAT. The induction of UCP1 expression in abdominal WAT is unusual because UCP1 is usually only found in brown adipose tissue. Fucoxanthin supplementation also improves insulin resistance and decreases blood glucose levels through the regulation of adipokine secretions from WAT and the upregulation of glucose transporter 4 expression and its translocation to muscle cell membranes.
• Anticancer effects of fucoxanthin and fucoxanthinol on colorectal cancer cell lines and colorectal cancer tissues

  Kazuto Takahashi, Masashi Hosokawa, Hiroyuki Kasajima, Kazuteru Hatanaka, Kazuhiro Kudo, Norihiko Shimoyama, Kazuo Miyashita

  ONCOLOGY LETTERS 10 3 1463 - 1467 2015年09月 [査読有り][通常論文]
   

  Colorectal cancer is one of the most malignant neoplasms worldwide. Fucoxanthin is a carotenoid present in the chloroplasts of brown seaweeds. In the present study, the anticancer effects of fucoxanthin and its metabolite, fucoxanthinol, on 6 colorectal cancer cell lines and 20 tissue samples from surgically resected Clinical colorectal cancer specimens were examined using a collagen-gel droplet embedded culture drug sensitivity test (CD-DST). The in vitro sensitivity to fiicoxanthin, fucoxanthinol and the anticancer drugs is expressed as T/C (%), where T is the absorbance of cells which stained by neutral red treated with carotenoids and C is the absorbance of non-staining cells. Fucoxanthin and fucoxanthinol decreased the T/C (%) of Caco-2, WiDr, HCI116, and DLD-1 cell lines at doses of 20 mu M. Fucoxanthinol also decreased the TIC (%) of SW620 cells, while the T/C (%) of Colo205 cells was not reduced by treatment with either carotenoid. Specifically, the TIC (%) of Caco-2 and Wi Dr cells, which were incubated in carotenoid-free medium for 6 days following treatment with 20 mu M fucaxanthinol for 24 h, was markedly decreased to 1.4 +/- 0.2 and 12.0 +/- 0.3%, respectively. Furthermore, fucoxanthin and fucoxanthinol decreased the TV (%) in colorectal cancer tissue samples. Notably, 20 mu M fucoxanthinol treatment resulted in a higher proportion of colorectal cancer samples with a T/C (%) of <50% (13/20, 65%) compared with samples treated with 20 mu M fucoxanthin (2/20, 10%). The median TIC (%) value of 35.1% for the 20 cancers specimens treated with 20 mu M fucoxanthinol was lower than the median T/C (%) values of 86.3% and 75.8% for those treated with fluorouracil and paclitaxel, respectively. These results suggested that fucoxanthin and fucoxanthinol may be of use as Chemotherapeutic agents in colorectal cancer.
• Fucoxanthinol, Metabolite of Fucoxanthin, Improves Obesity-Induced Inflammation in Adipocyte Cells

  Hayato Maeda, Shogo Kanno, Mei Kodate, Masashi Hosokawa, Kazuo Miyashita

  MARINE DRUGS 13 8 4799 - 4813 2015年08月 [査読有り][通常論文]
   

  Fucoxanthin (Fx) is a marine carotenoid found in edible brown seaweeds. We previously reported that dietary Fx metabolite into fucoxanthinol (FxOH), attenuates the weight gain of white adipose tissue of diabetic/obese KK-A(y) mice. In this study, to evaluate anti-diabetic effects of Fx, we investigated improving the effect of insulin resistance on the diabetic model of KK-A(y) mice. Furthermore, preventing the effect of FxOH on low-grade chronic inflammation related to oxidative stress was evaluated on 3T3-L1 adipocyte cells and a RAW264.7 macrophage cell co-culture system. A diet containing 0.1% Fx was fed to diabetic model KK-A(y) mice for three weeks, then glucose tolerance was observed. Fx diet significantly improved glucose tolerance compared with the control diet group. In in vitro studies, FxOH showed suppressed tumor necrosis factor- (TNF-), and monocyte chemotactic protein-1 (MCP-1) mRNA expression and protein levels in a co-culture of adipocyte and macrophage cells. These findings suggest that Fx ameliorates glucose tolerance in the diabetic model mice. Furthermore, FxOH, a metabolite of Fx, suppresses low-grade chronic inflammation in adipocyte cells.
• Structure of a novel monocyclic carotenoid, 3 ''-hydroxy-2 '-isopentenylsaproxanthin ((3R,2 ' S)-2 -(3-hydroxy-3 -methylbuty1)-3 ', 4 '-didehydro-1 ', 2 '-dihydro-beta, Psi-carotene-3, 1 '-diol), from a flavobacterium Gillisia limnaea strain DSM 15749

  Naoki Takatani, Tomoo Sawabe, Takashi Maoka, Kazuo Miyashita, Masashi Hosokawa

  BIOCATALYSIS AND AGRICULTURAL BIOTECHNOLOGY 4 2 174 - 179 2015年04月 [査読有り][通常論文]
   

  Gillisia lirtinaea strain DSM 15749 (=R-8282(T), =LMG21470,=CIP108418) is a Gram-negative, strictly aerobic, psychrophilic, and non-photosynthetic bacterium that belongs to the family Flavobacteriaceae, which was isolated from a microbial mat in Lake Fryxell, Antarctica (Van. Trapp en eI. al., 2004). The bacteriurn shows yellow colored colony, but the cat otenoid composition has never been determined yet. In this study, we elucidated the structure of carotenoids produced by the strain DSM 15749. G. lirtinaea strain DSM 15749 synthesized a novel monocyclic-type carotenoid, 3 ''-hydroxy-2'-isopentenylsaproxanthin ((3R, 2'S')-2 '-(3-hydroxy-3-methylbutyl)-3 '', 4'-didehydro-1', 2'-dihydro-beta, Psi-carotene-3, 1'-diol), as well as (3R, TR)-zeaxanthin. Furthermore, another monocyclic carotenoid, 2'-isopentenylsaproxanthin, was also detected in the strain DSM 15749. 3 ''-Hydroxy-2'-isopentenylsaproxanthin is "Chimera'like unique structures, in that one end group forms the same structure of zeaxanthin, and the other end group is the same as bacterioruberin which is produced by several extremophilic bacteria and archaea. This structure involved the hydroxy derivative of 2'-isopentenylsaproxanthin. The present study is the First report about the carotenoids produced by the genus Gillisto, of the family Flavobacteriaceae. (C) 2015 Elsevier Ltd. All rights reserved.
• 褐藻カロテノイド、フコキサンチン

  宮下和夫, 細川雅史

  FFIジャーナル 220 2 101 - 109 FFIジャーナル編集委員会 2015年 [査読無し][通常論文]
  
• Identification of a novel carotenoid, 2 '-isopentenylsaproxanthin, by Jejuia pallidilutea strain 11shimoA1 and its increased production under alkaline condition

  N. Takatani, K. Nishida, T. Sawabe, T. Maoka, K. Miyashita, M. Hosokawa

  APPLIED MICROBIOLOGY AND BIOTECHNOLOGY 98 15 6633 - 6640 2014年08月 [査読有り][通常論文]
   

  Carotenoids are a class of naturally occurring pigment, carrying out important biological functions in photosynthesis and involved in environmental responses including nutrition in organisms. Saproxanthin and myxol, which have monocyclic carotenoids with a gamma-carotene skeleton, have been reported to show a stronger antioxidant activity than those with beta-carotene and zeaxanthin. In this research, a yellow-orange bacterium of strain 11shimoA1 (JCM19538) was isolated from a seaweed collected at Nabeta Bay (Shizuoka, Japan). The 16S rRNA gene sequence of strain 11shimoA1 revealed more than 99.99 % similarity with those of Jejuia pallidilutea strains in the family Flavobacteriaceae. Strain 11shimoA1 synthesized two types of carotenoids. One of them was (3R, 3'R)-zeaxanthin with dicyclic structure and another was identified as (3R, 2'S)-2'-isopentenylsaproxanthin, a novel monocyclic carotenoid with pentenyl residue at C-2' position of saproxanthin, using FAB-MS, H-1 NMR, and CD analyses. Culturing strain 11shimoA1 in an alkaline medium at pH 9.2 resulted in a markedly increased in production of 2'-isopentenylsaproxanthin per dry cell weight, but a decreased in zeaxanthin production as compared to their respective production levels in medium with pH 7.0. These carotenoids are likely to play some roles in the adaptation of the bacterium to the environmental conditions.
• Source-sink manipulation of Camelina sativa L. related to grain yield under stressful environment of Hokkaido, Japan

  Kounosuke Fujita, Shohei Fujita, Takayuki Fujita, Satoshi Konishi, Johann Vollmann, Pravat Kumar Mohapatra, Masashi Hosokawa, Masato Kuwahara, Hirofumi Saneoka, Toshiaki Tadano

  SOIL SCIENCE AND PLANT NUTRITION 60 2 156 - 161 2014年04月 [査読有り][通常論文]
   

  Five cultivars of camelina species (Camelina sativa L.) were grown in the field at two levels of nitrogen (N) under the climate conditions of Hokkaido Island, Japan. N nutrition as well as the genetic difference between cultivars influenced biomass and grain production. Three cultivars responded positively to N application, but not the other two. Increase in grain yield was associated more with grain number than grain size. The plants accommodated the extra grains by increasing pod number. Irrespective of the N level in the soil, a linolenic acid concentration of the grain was very high at 31% of the total fatty acids. In cultivar Calena, lower leaves on the main stem were excised to find the effect of reduced source area on yield. Defoliation of lower leaves did not affect grain yield, indicating that these leaves do not contribute to source capacity of the plant during grain filling. However, removal of all leaves decreased grain yield to 70% relative to the control plant. In contrast to defoliation, shading of the whole panicle consisting of the pod shell and rachis was more effective in reducing grain yield. Shading of the panicle prior to the grain filling period at the levels of 33 and 6% irradiance relative to control decreased grain yield to 39 and 26%, respectively. These results suggested that the pod shell and rachis are more important source organs for photosynthetic carbon supply to grains than the upper leaves, and they can sustain grain filling in exigency. The presence of attributes like extended source area for grain filling and high alpha-linolenic acid content of leaves is an indicator for successful adaptation of Camelina in the stress-prone environment of Hokkaido Island.
• The extracts of Japanese willow tree species are effective forapoptotic desperation or differentiation of acute myeloid leukemia cells

  Kounosuke Fujita, Yuji Nomura, Masahiko Sawajiri, Pravat K. Mohapatra, Hany A. El-Shemy, Nguyen T. Nguyen, Masashi Hosokawa, Kazuo Miyashita, Teruo Maeda, Hirofumi Saneoka, Shohei Fujita, Takayuki Fujita

  PHARMACOGNOSY MAGAZINE 10 38 125 - 131 2014年04月 [査読有り][通常論文]
   

  Background: The antileukemic activity of hot water extract of plant parts of some Japanese willow tree species grown at different levels of nitrogen were examined. Materials and Methods: Water extracts of willow leaves were prepared for this studies in different level of nitrogen nutrition. Results: The extracts obtained from the leaves and stem exhibited anti-leukemic activities prominently. The crude hot water extracts of the young growing parts including apex, matured leaves and stem, killed the blasts of acute myeloid leukemia (AML) cells, (HL60 and NB4) after 48h incubation, however, such desperation was far less in the root extract. Similar to the plant parts, response of extracts obtained from different willow species was not identical; the proportion of dead cells relative to whole cells of the culture medium ranged from 21% to 93% among the species. Leaf extracts obtained from the responsive willow species decreased the live cell percentage and increased the dead cell percentage at higher level of nitrogen nutrition. The mode of desperation of leaf extract treated AML cells in such species appeared to be cell apoptosis as shown by binding with fluorescein isothiocyanate (FITC) -labeled Annexin V. Conclusion: Differentiation of alive AML cells continued unabated and apoptosis was poor when extract of an unresponsive species added to the culture medium.
• Regulation of Polyunsaturated Fatty Acid Biosynthesis by Seaweed Fucoxanthin and Its Metabolite in Cultured Hepatocytes

  Tsunehiro Aki, Masaya Yamamoto, Toshiaki Takahashi, Kohki Tomita, Rieko Toyoura, Kazuhiro Iwashita, Seiji Kawamoto, Masashi Hosokawa, Kazuo Miyashita, Kazuhisa Ono

  LIPIDS 49 2 133 - 141 2014年02月 [査読有り][通常論文]
   

  The effects of a seaweed carotenoid, fucoxanthin, and its physiological metabolite, fucoxanthinol, on the biosynthesis of polyunsaturated fatty acids (PUFA) were investigated using cultured rat hepatoma BRL-3A. The metabolism of alpha-linolenic acid (18:3n-3) was suppressed by the addition of these carotenoids, resulting in a decrease in the content of eicosapentaenoic acid (20:5n-3), which suggested a down-regulation of metabolic enzymes such as fatty acid desaturase and elongase. An increase in the content of docosahexaenoic acid (22:6n-3), as observed in previous studies in vivo, might be a buffering action to maintain the membrane fluidity. The suppressive effect of fucoxanthinol on a dagger 6 fatty acid desaturase was not at the level of gene expression but due to specific modifications of the protein via a ubiquitin-proteasome system. A proteomic analysis revealed several factors such as phosphatidylethanolamine-binding protein that might be involved in the observed action of fucoxanthin. These findings will contribute to studies on the elucidation of the precise molecular mechanisms underlying the regulation of PUFA biosynthesis by fucoxanthin.
• Carotenoids as a Nutraceutical Therapy for Visceral Obesity

  Kazuo Miyashita, Masashi Hosokawa

  Nutrition in the Prevention and Treatment of Abdominal Obesity 329 - 340 2014年 [査読有り][通常論文]
   

  Obesity is linked to several diseases with a rapidly growing prevalence in most of the world. A few molecular targets are key to the successful development of antiobesity therapeutics: one of the most promising targets for activation is uncoupling protein 1 (UCP 1). Fucoxanthin, a marine carotenoid found in edible brown seaweeds, shows antiobesity effect that are mainly based on increasing energy expenditure in abdominal white adipose tissue (WAT) through UCP 1 induction. The key fucoxanthin structure involved in the antiobesity effect is suggested to be carotenoid end of the polyene chromophore containing an allenic bond. Fucoxanthin also improves insulin resistance and decreases blood glucose level through regulating adipocytokine secretions from abdominal WAT. Another important molecular mechanism for improving glucose utilization by fucoxanthin is solute carrier family 2, facilitated glucose transporter member 4 (GLUT4) upregulation and its translocation to the cell membrane from the cytosol. Interestingly, fucoxanthin effects are seen only in subjects with obesity and metabolic disorders, and not in normal healthy individuals. Therefore, fucoxanthin is a promising nutraceutical drug for treating obesity and related metabolic disorders. © 2014 Elsevier Inc. All rights reserved.
• Studies on chemical composition of three species of Enteromorpha

  K. Ganesan, K. Suresh Kumar, P. V. Subba Rao, Y. Tsukui, N. Bhaskar, M. Hosokawa, K. Miyashita

  Biomedicine and Preventive Nutrition 4 3 365 - 369 2014年 [査読有り][通常論文]
   

  Studies on proximate, mineral, fatty and amino acid composition of edible Enteromorpha species, viz. Enteromorphacompressa, Enteromorphalinza and Enteromorphatubulosa, collected from the Northwest coast of India, revealed for species-dependent nutrient composition variation. The present study showed a higher amount of sugar (51.05. ±. 1.22%), protein (19.09. ±. 0.91%) and lipid content (5.56. ±. 0.16%) E.tubulosa. Amongst the seventeen elements analyzed (Ca, K, Mg, Na, P, As, Cd, Co, Cu, Fe, Hg, Mn, Mo, Ni, Zn, Cr, Pb), all three species showed a higher amount of calcium content. E.compressa was obtained with rich amount of macro-elements (11.42. ±. 0.017. g/100. g dry wt), while maximum micro- and trace-elements (81.51. ±. 6.65. mg/100. g dry wt) were recorded in E.linza. Amino acid analysis revealed seven out of the 10 essential amino acids were present either in excess or at-par with the reference proteins. Moreover, all the three species studied possessed relatively high n-3 fatty acids additionally they had more unsaturated fatty acids than saturate ones, except in E.compressa. Therefore, based on the present investigation, it could be stated that the three species studied could be used as food supplements to improve the nutritive value in the omnivorous diet. © 2014 Elsevier Masson SAS.
• Draft genome sequences of marine flavobacterium Nonlabens strains NR17, NR24, NR27, NR32, NR33, and Ara13

  Masato Nakanishi, Pedro Meirelles, Ryohei Suzuki, Naoki Takatani, Sayaka Mino, Wataru Suda, Kenshiro Oshima, Masahira Hattori, Moriya Ohkuma, Masashi Hosokawa, Kazuo Miyashita, Fabiano L. Thompson, Ako Niwa, Toko Sawabe, Tomoo Sawabe

  Genome Announcements 2 6 2014年 [査読有り][通常論文]
   

  Here, we present the draft genome sequences of six carotenoid producers affiliated with Nonlabens spp. isolated from marine environments in both the northern and southern parts of Japan. The genomic information will help to elucidate the function and evolution of carotenoid synthetic gene clusters not only in the genus Nonlabens but also in the family Flavobacteriaceae.
• Draft genome sequences of marine flavobacterium Algibacter lectus strains SS8 and NR4

  Naoki Takatani, Masato Nakanishi, Pedro Meirelles, Sayaka Mino, Wataru Suda, Kenshiro Oshima, Masahira Hattori, Moriya Ohkuma, Masashi Hosokawa, Kazuo Miyashita, Fabiano L. Thompson, Ako Niwa, Toko Sawabe, Tomoo Sawabe

  Genome Announcements 2 6 2014年 [査読有り][通常論文]
   

  Here, we present the draft genome sequences of a zeaxanthin-producing flavobacterium, Algibacter lectus strains SS8 and NR4, isolated from coastal sediment and rock surfaces in Hakodate, Japan, respectively. This genomic information represents the first Algibacter genome sequences, which will help us to elucidate the biology and evolution of Flavobacteriaceae bacteria.
• Draft genome sequence of marine flavobacterium Jejuia pallidilutea strain 11shimoA1 and pigmentation mutants

  Naoki Takatani, Masato Nakanishi, Pedro Meirelles, Sayaka Mino, Wataru Suda, Kenshiro Oshima, Masahira Hattori, Moriya Ohkuma, Masashi Hosokawa, Kazuo Miyashita, Fabiano L. Thompson, Ako Niwa, Toko Sawabe, Tomoo Sawabe

  Genome Announcements 2 6 2014年 [査読有り][通常論文]
   

  Here, we present the draft genome sequence of a novel carotenoid 2'-isopentenylsaproxanthin producer, Jejuia pallidilutea strain 11shimoA1, isolated from the surface of seaweed in Japan, and the ethyl methanesulfonate-induced pigmentation mutants. This genomic information will help to not only elucidate the 2'-isopentenylsaproxanthin biosynthetic pathway but also understand the evolution of flavobacteria.
• Fucoxanthin: A Marine Carotenoid Exerting Anti-Cancer Effects by Affecting Multiple Mechanisms

  Sangeetha Ravi Kumar, Masashi Hosokawa, Kazuo Miyashita

  MARINE DRUGS 11 12 5130 - 5147 2013年12月 [査読有り][通常論文]
   

  Fucoxanthin is a marine carotenoid exhibiting several health benefits. The anti-cancer effect of fucoxanthin and its deacetylated metabolite, fucoxanthinol, is well documented. In view of its potent anti-carcinogenic activity, the need to understand the underlying mechanisms has gained prominence. Towards achieving this goal, several researchers have carried out studies in various cell lines and in vivo and have deciphered that fucoxanthin exerts its anti-proliferative and cancer preventing influence via different molecules and pathways including the Bcl-2 proteins, MAPK, NFB, Caspases, GADD45, and several other molecules that are involved in either cell cycle arrest, apoptosis, or metastasis. Thus, in addition to decreasing the frequency of occurrence and growth of tumours, fucoxanthin has a cytotoxic effect on cancer cells. Some studies show that this effect is selective, i.e., fucoxanthin has the capability to target cancer cells only, leaving normal physiological cells unaffected/less affected. Hence, fucoxanthin and its metabolites show great promise as chemotherapeutic agents in cancer.
• Chemical and nutritional characteristics of brown seaweed lipids: A review

  Kazuo Miyashita, Nana Mikami, Masashi Hosokawa

  JOURNAL OF FUNCTIONAL FOODS 5 4 1507 - 1517 2013年10月 [査読有り][通常論文]
   

  Several brown seaweeds show high total lipids (TL) contents, ranging from 10 to 20 wt.% per dry weight. The main lipid class is glycoglycerolipids (GL), which are rich in 18:4n-3, 20:5n-3 and 20:4n-6. Brown seaweed TL also contains fucoxanthin as a key functional compound. Despite the high levels of 18:4n-3, 20:5n-3 and 20:4n-6, brown seaweed lipids are stable to oxidation. Their high oxidative stability is partly related to the presence of these polyunsaturated fatty acids in their GL forms. Brown seaweed lipids show anti-obesity and anti-diabetic effects, which are mainly due to the up-regulatory effect of fucoxanthin on energy expenditure in abdominal white adipose tissue and glucose utilization in muscle. (C) 2013 Published by Elsevier Ltd.
• Oxidative Stability of Lipids Rich in EPA and DHA Extracted from Fermented Scallop Ovary

  Naohiro Hamaoka, Junki Shimajiri, Masayuki Abe, Masashi Hosokawa, Kazuo Miyashita

  JOURNAL OF FOOD SCIENCE 78 9 C1348 - C1353 2013年09月 [査読有り][通常論文]
   

  A novel seafood paste was developed by the fermentation of scallop ovary using rice malt (koji) and yeast culture. Chemical analysis of the product showed the formation of high level of free amino acids and organic acids during the fermentation. The product color and flavor resembled to Japanese traditional soybean miso. The contents of total lipids (TLs) extracted from the fermented products were ranged from 9.18% to 11.59% or 11.38% to 13.57%/dry sample weight. Although the TL was rich in oxidatively unstable polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), little decrease was found in these PUFAs during the fermentation, showing the high oxidative stability of the TL from the fermented scallop ovary. Moreover, the oxidative stability of the TL extracted from the fermented products increased with increasing the fermentation time. This would be mainly due to the formation of lipid soluble antioxidants such as tocopherols, which might be derived from yeast used for fermentation.
• Synergistic antioxidant activity of milk sphingomyeline and its sphingoid base with α-tocopherol on fish oil triacylglycerol.

  Shimajiri J, Shiota M, Hosokawa M, Miyashita K

  Journal of agricultural and food chemistry 61 33 7969 - 7975 33 2013年08月 [査読有り][通常論文]
   

  The effects of milk phospholipids (PLs), sphingolipids (SLs), and their sphingoid backbone on the oxidation of fish oil triacylglycerol (TAG) were examined with or without alpha-tocopherol. All compounds had little effect on the TAG oxidation in the absence of alpha-tocopherol. On the other hand, they could act synergistically with alpha-tocopherol. The highest synergistic activity was shown by sphingoid bases, followed by sphingomyelin (SPM) and other amine-containing PLs and SLs. This result showed that the synergistic activity increased with an increasing concentration of amine group of PLs, SLs, or sphingoid bases in the reaction mixture. The comparison of changes in alpha-tocopherol content in fish oil TAG and tricaprylin suggested that antioxidant compounds would be formed from the amine group and the lipid oxidation products in a mild oxidation condition controlled by alpha-tocopherol.
• Seasonal variations of total lipids, fatty acid composition, and fucoxanthin contents of Sargassum horneri (Turner) and Cystoseira hakodatensis (Yendo) from the northern seashore of Japan

  Masatoshi Nomura, Hiroyuki Kamogawa, Eko Susanto, Chikara Kawagoe, Hajime Yasui, Naotsune Saga, Masashi Hosokawa, Kazuo Miyashita

  JOURNAL OF APPLIED PHYCOLOGY 25 4 1159 - 1169 2013年08月 [査読有り][通常論文]
   

  The present study describes the seasonal changes in lipid components of two brown algae, Sargassum horneri (Turner) and Cystoseira hakodatensis (Yendo), with specific reference to fucoxanthin (Fx) and n-3 (omega-3) polyunsaturated fatty acids (PUFAs). Young thalli of S. horneri were collected from different places, Nesaki and Matsushima, and cultivated in the same place. Total lipids (TL) and Fx contents of S. horneri increased from October or November and reached a maximum in January and then decreased thereafter. TL and Fx of S. horneri originated from Matsushima were always higher than those originated from Nesaki, suggesting that genetic variation might be a reason for the different TL and Fx contents found in both S. horneri seeds from different origin. Similar seasonal variation in the TL and Fx content has been more clearly observed in C. hakodatensis. Maximum TL content of S. horneri and C. hakodatensis reached to more than 14 and 15 % in winter season. These values were much higher than those found in previous studies showing TL content range from 1 to 5 %. Fatty acid composition of lipids from S. horneri and C. hakodatensis also changed seasonally. Total monounsaturated fatty acids showed the lower values from January to April, while there were no big variations in total saturated fatty acids and total n-6 PUFAs. On the other hand, total n-3 PUFAs became highest in winter. Overall, S. horneri and C. hakodatensis harvested from winter to spring will be used as good n-3 PUFA source with high levels of TL and Fx.
• Biosynthetic Pathway and Health Benefits of Fucoxanthin, an Algae-Specific Xanthophyll in Brown Seaweeds

  Koji Mikami, Masashi Hosokawa

  INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 14 7 13763 - 13781 2013年07月 [査読有り][通常論文]
   

  Fucoxanthin is the main carotenoid produced in brown algae as a component of the light-harvesting complex for photosynthesis and photoprotection. In contrast to the complete elucidation of the carotenoid biosynthetic pathways in red and green algae, the biosynthetic pathway of fucoxanthin in brown algae is not fully understood. Recently, two models for the fucoxanthin biosynthetic pathway have been proposed in unicellular diatoms; however, there is no such information for the pathway in brown seaweeds to date. Here, we propose a biosynthetic pathway for fucoxanthin in the brown seaweed, Ectocarpus siliculosus, derived from comparison of carotenogenic genes in its sequenced genome with those in the genomes of two diatoms, Thalassiosira pseudonana and Phaeodactylum tricornutum. Currently, fucoxanthin is receiving attention, due to its potential benefits for human health. Therefore, new knowledge regarding the medical and nutraceutical properties of fucoxanthin from brown seaweeds is also summarized here.
• Down-Regulation of Hepatic Stearoyl-CoA Desaturase-1 Expression by Fucoxanthin via Leptin Signaling in Diabetic/Obese KK-A (y) Mice

  Fumiaki Beppu, Masashi Hosokawa, Mi-Jin Yim, Taro Shinoda, Kazuo Miyashita

  LIPIDS 48 5 449 - 455 2013年05月 [査読有り][通常論文]
   

  Stearoyl-coenzyme A desaturase-1 (SCD1) is a rate-limiting enzyme that catalyzes the biosynthesis of monounsaturated fatty acids from saturated fatty acids. Recently, SCD1 down-regulation has been implicated in the prevention of obesity, and the improvement of insulin and leptin sensitivity. In this study, we examined the effect of fucoxanthin, a marine carotenoid, on hepatic SCD1 in obese mouse models of hyperleptinemia KK-A (y) and leptin-deficiency ob/ob. In KK-A (y) mice, providing a diet containing 0.2 % fucoxanthin for 2 weeks markedly suppressed SCD1 mRNA and protein expressions in the liver. The fatty acid composition of liver lipids was also affected by an observed decrease in the ratio of oleic acid to stearic acid. Furthermore, serum leptin levels were significantly decreased in hyperleptinemia KK-A (y) mice after 2 weeks of fucoxanthin feeding. However, the suppressive effects of fucoxanthin on hepatic SCD1 and body weight gain were not observed in ob/ob mice. These results show that fucoxanthin down-regulates SCD1 expression and alters fatty acid composition of the liver via regulation of leptin signaling in hyperleptinemia KK-A (y) mice but not in leptin-deficient ob/ob mice.
• Substrate and Droplet Size: Important Factors for Understanding Aqueous Lipid Oxidation

  Kazuo Miyashita, Masashi Hosokawa

  Lipid Oxidation: Challenges in Food Systems 155 - 176 2013年04月02日 [査読有り][通常論文]
   

  Lipid oxidation generally proceeds from the interface to the interior of the oil droplet in Oil-in-Water (O/W) emulsions therefore, the oxidation of lipids at the interface is an important factor to predict the oxidative stability of lipids in emulsion. In emulsions, the membranes surrounding the emulsion droplets consist of surface-active substances such as emulsifiers and/or proteins, together with lipids and water. They can sometimes provide a protective barrier for the penetration and diffusion of metals or radicals that initiate lipid oxidation. Therefore, the chemical and physical nature of the emulsifier and proteins is an important factor for the protection of PUFAs against oxidation in the aqueous phase. The different affinities of antioxidants and/or pro-oxidants to the interface are another important factor. Overall, the major factors affecting lipid oxidation at the interface are: affinity (partition) of antioxidants and/or pro-oxidants to the interface and chemical, physical, and stereo chemical susceptibility of interface lipids to oxidation. The behavior of antioxidants and pro-oxidants at the interface is related to their polarity and electrical charge. The oxidative stability of lipids at the interface is influenced by the size and concentration of the emulsion droplets, the thickness and the packing degree of interface molecules, and the extent of droplet-droplet interactions. Moreover, substrate lipid class and the degree of unsaturation have been reported to affect the oxidative characteristics at the interface. This chapter focuses on the effect of emulsifier, substrate lipids, and droplet size as a series of factors that affect lipid oxidation at the interface in O/W emulsion.
• Bovine lactoferrin reduces visceral fat and liver triglycerides in ICR mice

  Satoru Morishita, Tomoji Ono, Chikako Fujisaki, Yasuharu Ishihara, Michiaki Murakoshi, Hisanori Kato, Masashi Hosokawa, Kazuo Miyashita, Keikichi Sugiyama, Hoyoku Nishino

  JOURNAL OF OLEO SCIENCE 62 2 97 - 103 2013年02月 [査読有り][通常論文]
   

  Lactoferrin (LF) is a multi-functional glycoprotein found in milk. In a previous clinical trial, we showed that enteric-coated bovine LF (bLF) tablets could reduce visceral fat accumulation. We also showed that bLF had anti-adipogenic activity in vitro. However, the mechanisms responsible for these phenomena remain unclear. In this study, we established an animal model of visceral fat reduction via oral bLF administration. We used gastric intubation to ensure that LF was absorbed in the small intestine. bLF administration for 4 weeks significantly reduced mesenteric fat tissue (P < 0.05) and hepatic triglyceride levels (P < 0.01). Furthermore, these two outcomes were positively correlated (R = 0.581, P < 0.05). Overall, these findings suggest that bLF affects mesenteric adipocytes and fatty acid metabolism in the liver.
• Marine nutraceuticals: Sources, recovery and effective utilization

  Nimish Mol Stephen, N. Bhaskar, M. Hosokawa, K. Miyashita

  Advances in Food Science and Technology 1 - 17 2013年01月 

  The unique and phenomenal biodiversity of the marine environment makes seafoods, including marine macro/micro algae, a large a pool of novel and bioactive molecules apart from being nutritious food items. Till recently, marine nutraceuticals were largely limited to popular fish oils that afford n-3 fatty acids and of late to some carotenoids. Recent advances in biotechnological processes and their application for product development have resulted in identification of several evidence-based marine nutrients that have nutraceutical potential. Further, the uniqueness of marine environment confers a dual role of a functional ingredient and a nutraceutical to most of the marine bioactive molecules because of which they can be termed as marine functional materials. Most of these marine functional materials form basis for functional foods, dietary and nutritional supplements, nutraceuticals, probiotics, prebiotics and other functional health enhancing food products. Further, this ability to manipulate the formulation of a food would allow a greater creativity in designing new, healthful and specific food products. With the world food consumption transiting from traditional foods and herbal remedies to designer healthful functional foods/nutraceuticals with guaranteed health effects, such an approach would lead to a significant increase in the utilization of marine nutraceuticals.In the foregoing sections, an attempt will be made first to discuss the various marine functional materials. As n-3 polyunsaturated fatty acids (PUFA) mainly eicosapentenoic acid (EPA) and docosahexaenoic acid (DHA) have been thoroughly explored for their nutraceutical potential and functionality, the current chapter mainly focuses on bioactive molecules in addition to PUFA, their possible recovery methods and general analysis of target based applications for their effective utilization. © 2012 by Nova Science Publishers, Inc. All rights reserved.
• Chemopreventive Effects of Astaxanthin on Inflammatory Bowel Disease and Inflammation-Related Colon Carcinogenesis

  Masashi Hosokawa, Yumiko Yasui

  Carotenoids and Vitamin A in Translational Medicine 289 - 306 2013年01月01日 

  Carotenoids are a family of natural pigments with at least 750 members. They possess a polyisoprenoid structure and are synthesized by plants, seaweeds, and microorganisms, but not by animals. Fruits and vegetables are the major sources of dietary carotenoids [1]. Yellow-orange vegetables and fruits provide a-and β-carotene, orange fruits provide β-cryptoxanthin, dark green leaves and vegetables.
• Fucoxanthin as potential nutraceutical for obesity therapy: A Review.

  Miyashita K, Maeda H, Nishikawa S, Tsukui T, Widjaja-Adhi MA-K, Hosokawa M

  Carotenoid Sci. 17 1 - 7 2013年 [査読有り][通常論文]
  
• Effects of dietary fucoxanthin on cholesterol metabolism in diabetic/obese KK-A(y) mice

  Fumiaki Beppu, Masashi Hosokawa, Yoshimi Niwano, Kazuo Miyashita

  LIPIDS IN HEALTH AND DISEASE 11 112  2012年09月 [査読有り][通常論文]
   

  Background: Fucoxanthin is a xanthophyll present in brown seaweeds and has several beneficial effects, including anti-obesity and anti-diabetic effects. However, we and another group previously observed that fucoxanthin increases serum cholesterol levels in rodents. Cholesterol is an important component of cell membranes and biosynthesis of bile acids. Serum cholesterol levels are also closely associated with atherosclerosis. Therefore, we sought to identify the mechanism underlying the increase in serum cholesterol levels by fucoxanthin. Methods: Diabetic/obese KK-A(y) mice were fed a diet containing 0.2% fucoxanthin for 4 weeks. The mice were sacrificed, and total blood samples were collected for the measurement of serum total cholesterol, HDL-cholesterol and non-HDL-cholesterol levels. Cholesterol content in tissues was also analyzed. Real-time PCR and Western blotting were performed to determine hepatic mRNA and protein expression of genes involved in cholesterol metabolism, respectively. Results: Dietary fucoxanthin significantly increased serum HDL and non-HDL cholesterol levels, and reduced hepatic cholesterol content. In liver, the expression of SREBP1, SREBP2 and their target genes involved in cholesterol biosynthesis significantly increased and tended to increase in the fucoxanthin-fed mice, respectively. In contrast, hepatic levels of LDLR and SR-B1 proteins which is important factors for LDL-cholesterol and HDL-cholesterol uptake in the liver from serum, decreased to 60% and 80% in the fucoxanthin-fed mice, respectively, compared with the control mice. Further, we found that dietary fucoxanthin significantly increased the mRNA expression of proprotein convertase subtilisin/kexin type 9 (PCSK9), which enhances intracellular degradation of LDLR in lysosomes. Conclusions: Fucoxanthin increased HDL-cholesterol and non-HDL-cholesterol levels in KK-A(y) mice by inducing SREBP expression and reduced cholesterol uptake in the liver via down-regulation of LDLR and SR-B1, resulted in increased serum cholesterol in the mice.
• Oxidative Stability of Glyceroglycolipids Containing Polyunsaturated Fatty Acids

  Tomoyo Yamaguchi, Rumiko Sugimura, Junki Shimajiri, Masatake Suda, Masayuki Abe, Masashi Hosokawa, Kazuo Miyashita

  JOURNAL OF OLEO SCIENCE 61 9 505 - 513 2012年09月 [査読有り][通常論文]
   

  The oxidative stability of glyceroglycolipids (GLs) from spinach or brown edible seaweed (Laminaria japonica) was compared with those of phosphatidylcholines (PCs) from salmon roe and triacyglycerols (TAGs) from soybean oil or sardine oil. All the lipids were subjected to autoxidation after removing oxidants and/or antioxidants such as chlorophylls, tocopherols, and carotenoids. The oxidative stability of the lipids decreased with increasing number of bisallylic positions in the molecule. Due to the higher mean number of bisallylic positions, salmon roe PC and sardine oil TAG were oxidized more rapidly than soybean oil TAG. Spinach GL and brown edible seaweed GL showed the same oxidative stability as that found in soybean oil TAG, although the mean number of bisallylic positions of both GLs was much higher than that of soybean oil TAG and approached the number found in sardine oil TAG and salmon roe PC. The present study indicates the important effect of galactosyl and sulfoquinovosyl moieties on the oxidative stability of GL.
• Effect of Caffeine and Capsaicin on the Blood Glucose Levels of Obese/Diabetic KK-A(gamma) Mice

  Tomoyuki Okumura, Takayuki Tsukui, Masashi Hosokawa, Kazuo Miyashita

  JOURNAL OF OLEO SCIENCE 61 9 515 - 523 2012年09月 [査読有り][通常論文]
   

  The present study is aimed to measure the effect of caffeine and capsaicin on the blood glucose level of obese/diabetic model mice. The blood glucose level of KK-A(gamma) obese/diabetic mice decreased significantly after dietary supplementations with less than 0.031% caffeine and less than 0.0042% capsaicin, while both food ingredients and the combination had little effect on body weight gain and abdominal white adipose tissue (WAT) weight at this dose. The blood glucose level of the control mice was 234.4 mg/dL at 10 days after feeding and it increased to 500.6 mg/dL after 28 days, while levels after intake of caffeine, capsaicin, and both together increased from 180, 131.6, and 140 mg/dL to 183.7, 255.1, and 151.6 mg/dL, respectively. The anti-diabetic activity of caffeine and capsaicin was confirmed by a decrease in total drinking water and in the blood insulin level.
• Stability of Fucoxanthin in Dried Undaria Pinnatifida (Wakame) and Baked Products (Scones) Containing Wakame Powder

  Rumiko Sugimura, Masatake Suda, Ayumi Sho, Tomoya Takahashi, Tokutake Sashima, Masayuki Abe, Masashi Hosokawa, Kazuo Miyashita

  FOOD SCIENCE AND TECHNOLOGY RESEARCH 18 5 687 - 693 2012年09月 [査読有り][通常論文]
   

  Stability of fucoxanthin was assessed in dried Undaria pinnatifida (wakame). After 210 days storage of dried wakame in the dark at 50 degrees C, the stability of fucoxanthin was higher than that of purified fucoxanthin incubated at both 20 degrees C and 40 degrees C. Furthermore, we analyzed the stability of fucoxanthin in scones containing 0.5 - 2 wt% commercial dried wakame powder. More than 85% of the fucoxanthin remained unchanged in the scones after heating the dough at 190 degrees C for 30 min. Sensory analysis indicated that although the addition of wakame powder darkened the appearance and strengthened both the taste and smell of the scones, they remained acceptable. Furthermore, overall sensory scores showed that scones containing 0.5 wt% and 2 wt% wakame powder were more favorable than control scones.
• Effects of dietary fucoxanthin on cholesterol metabolism in diabetic/obese KK-A(y) mice

  Fumiaki Beppu, Masashi Hosokawa, Yoshimi Niwano, Kazuo Miyashita

  LIPIDS IN HEALTH AND DISEASE 11 112  2012年09月 [査読有り][通常論文]
   

  Background: Fucoxanthin is a xanthophyll present in brown seaweeds and has several beneficial effects, including anti-obesity and anti-diabetic effects. However, we and another group previously observed that fucoxanthin increases serum cholesterol levels in rodents. Cholesterol is an important component of cell membranes and biosynthesis of bile acids. Serum cholesterol levels are also closely associated with atherosclerosis. Therefore, we sought to identify the mechanism underlying the increase in serum cholesterol levels by fucoxanthin.Methods: Diabetic/obese KK-A(y) mice were fed a diet containing 0.2% fucoxanthin for 4 weeks. The mice were sacrificed, and total blood samples were collected for the measurement of serum total cholesterol, HDL-cholesterol and non-HDL-cholesterol levels. Cholesterol content in tissues was also analyzed. Real-time PCR and Western blotting were performed to determine hepatic mRNA and protein expression of genes involved in cholesterol metabolism, respectively.Results: Dietary fucoxanthin significantly increased serum HDL and non-HDL cholesterol levels, and reduced hepatic cholesterol content. In liver, the expression of SREBP1, SREBP2 and their target genes involved in cholesterol biosynthesis significantly increased and tended to increase in the fucoxanthin-fed mice, respectively. In contrast, hepatic levels of LDLR and SR-B1 proteins which is important factors for LDL-cholesterol and HDL-cholesterol uptake in the liver from serum, decreased to 60% and 80% in the fucoxanthin-fed mice, respectively, compared with the control mice. Further, we found that dietary fucoxanthin significantly increased the mRNA expression of proprotein convertase subtilisin/kexin type 9 (PCSK9), which enhances intracellular degradation of LDLR in lysosomes.Conclusions: Fucoxanthin increased HDL-cholesterol and non-HDL-cholesterol levels in KK-A(y) mice by inducing SREBP expression and reduced cholesterol uptake in the liver via down-regulation of LDLR and SR-B1, resulted in increased serum cholesterol in the mice.
• Dietary Combination of Fish Oil and Taurine Decreases Fat Accumulation and Ameliorates Blood Glucose Levels in Type 2 Diabetic/Obese KK-A(y) Mice

  Nana Mikami, Masashi Hosokawa, Kazuo Miyashita

  JOURNAL OF FOOD SCIENCE 77 6 H114 - H120 2012年06月 [査読有り][通常論文]
   

  n-3 Polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and taurine are functional compounds abundantly present in seafoods. In this study, we examined the combined effects of EPA- and DHA-rich fish oil and taurine on white adipose tissue (WAT) weight and blood glucose levels in diabetic/obese KK-A(y) mice. After a 4-wk administration of experimental diets (soybean oil or fish oil, supplemented with 0%, 2%, or 4% taurine), the increase in WAT weight of the mice fed the "fish oil + 4% taurine" diet was significantly suppressed compared to the "soybean oil + 4% taurine" and "fish oil only" diets. Serum triglycerides, free fatty acids, and total cholesterol levels decreased by fish oil administration. In addition, fish oil and taurine increased the activity of acyl-CoA oxidase, which is the rate-limiting enzyme of peroxisomal beta-oxidation, increased in the liver of KK-A(y) mice. The activity of fatty acid synthase decreased by fish oil diets. Furthermore, blood glucose and insulin levels were significantly lower in the mice fed fish oil than in the soybean oil-fed mice. In fish oil + 4% taurine group, hyperglycemia and hyperinsulinemia were effectively improved in KK-A(y) mice compared to the fish oil only groups. In particular, the combination of fish oil and taurine enhanced the glucose transporter 4 (GLUT4) distribution in the plasma membrane of muscle tissue. These results suggest that EPA- and DHA-rich fish oil, especially in combination with taurine, exhibits preventive effects on WAT weight gain and hyperglycemia in diabetic/obese KK-A(y) mice.
• Fucoxanthin promotes translocation and induction of glucose transporter 4 in skeletal muscles of diabetic/obese KK-A(y) mice

  Sho Nishikawa, Masashi Hosokawa, Kazuo Miyashita

  PHYTOMEDICINE 19 5 389 - 394 2012年03月 [査読有り][通常論文]
   

  Fucoxanthin (Fx) isolated from Undaria pinnatifida suppresses the development of hyperglycemia and hyperinsulinemia of diabetic/obese KK-A(y) mice after 2 weeks of feeding 0.2% Fx-containing diet. In the soleus muscle of KK-A(y) mice that were fed Fx, glucose transporter 4 (GLUT4) translocation to plasma membranes from cytosol was promoted. On the other hand, Fx increased GLUT4 expression levels in the extensor digitorum longus (EDL) muscle, although GLUT4 translocation tended to increase. The expression levels of insulin receptor (IR) mRNA and phosphorylation of Akt, which are in upstream of the insulin signaling pathway regulating GLUT4 translocation, were also enhanced in the soleus and EDL muscles of the mice fed Fx. Furthermore, Fx induced peroxisome proliferator activated receptor gamma coactivator-1 alpha (PGC-1 alpha), which has been reported to increase GLUT4 expression, in both soleus and EDL muscles. These results suggest that in diabetic/obese KK-A(y) mice, Fx improves hyperglycemia by activating the insulin signaling pathway, including GLUT4 translocation, and inducing GLUT4 expression in the soleus and EDL muscles, respectively, of diabetic/obese KK-A(y) mice. (C) 2011 Elsevier GmbH. All rights reserved.
• Skin Photoprotection by Marine Carotenoids

  Masashi Hosokawa

  Marine Cosmeceuticals: Trends and Prospects 2012年
• Therapeutic Effect of Fucoxanthin on Metabolic Syndrome and Type 2 Diabetes

  Kazuo Miyashita, Show Nishikawa, Masashi Hosokawa

  Nutritional and Therapeutic Interventions for Diabetes and Metabolic Syndrome 367 - 379 2012年 [査読無し][通常論文]
  
• Analyses on the functions and developments for the utilization technology of health functional components derived from fisheries products -Effective utilization and development for the next stage-

  Hideki Ushio, Naohiro Gotoh, Reiko Nagasaka, Masashi Hosokawa

  Nippon Suisan Gakkaishi (Japanese Edition) 78 5 1053 - 1056 2012年 [査読無し][通常論文]
  
• Carotenoid Profile of Edible Japanese Seaweeds: An Improved HPLC Method for Separation of Major Carotenoids

  Masaru Terasaki, Bhaskar Narayan, Hiroyuki Kamogawa, Masatoshi Nomura, Nimish Mol Stephen, Chikara Kawagoe, Masashi Hosokawa, Kazuo Miyashita

  JOURNAL OF AQUATIC FOOD PRODUCT TECHNOLOGY 21 5 468 - 479 2012年 [査読有り][通常論文]
   

  An improved multi-step gradient reverse phase high performance liquid chromatography (HPLC) method to simultaneously separate major carotenoids from natural as well as food samples was developed. Quantitative profiling of carotenoid compounds was carried out on three edible brown seaweeds (Sargassum horneri, Cystoseira hakodatensis, and Undaria pinnatifida) and three red seaweeds (Gracilaria vermiculophylla, Grateloupia asiatica, and Grateloupia livida). Fucoxanthin (Fx) was detected in all the brown seaweeds with quantities (mg g-1 dry weight [dwt]) ranging from 1.3 +/- 0.3 in C. hakodatensis to 2.4 +/- 0.1 in S. horneri. U. pinnatifida, commonly known as wakame, had a Fx content of 2.3 +/- 0.1 mg g-1 dwt. In the case of red seaweeds, zeaxanthin (Zx) was the major carotenoid, and G. vermiculophylla had the highest Zx content (80.2 mu g g-1 dwt) among the red seaweeds apart from small amounts of Fx (9.1 mu g g-1 dwt). Similarly, the other two species of red seaweeds, G. asiatica and G. livida, contained (mu g g-1 dwt) lutein (Lut), Fx, and Zx as the major carotenoids (G. asiatica: Lut 10.4, Fx 1.5, Zx 1.1; G. livida: Lut 9.3, Fx 3.5, Zx 1.0). The results suggest the usefulness of edible varieties (barring wakame) of seaweeds as dietary sources of carotenoids.
• In vivo antioxidant activity of fucoxanthin on obese/diabetes KK-Ay mice.

  S. Iwasaki, M. A-K. Widjaja-Adhi, A. Koide, T. Kaga, S. Nakano, F. Beppu, M. Hosokawa, K. Miyashita

  Food Nutr. Sci. 3 1491 - 1499 2012年 [査読有り][通常論文]
  
• Brown Seaweed Lipids as Potential Source of Omega-3 PUFA in Biological Systems

  Kazuo Miyashita, Bhaskar Narayan, Takayuki Tsukui, Hiroyuki Kamogawa, Masayuki Abe, Masashi Hosokawa

  Handbook of Marine Macroalgae: Biotechnology and Applied Phycology 329 - 339 2011年11月21日 [査読無し][通常論文]
  
• Algal Carotenoids as Potent Antioxidants

  Kazuo Miyashita, M. Airanthi K. Widjaja-Adhi, Masayuki Abe, Masashi Hosokawa

  Handbook of Marine Macroalgae: Biotechnology and Applied Phycology 403 - 414 2011年11月21日 [査読無し][通常論文]
  
• Cancer Chemopreventive Ability of Conjugated Linolenic Acids

  Takuji Tanaka, Masashi Hosokawa, Yumiko Yasui, Rikako Ishigamori, Kazuo Miyashita

  INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 12 11 7495 - 7509 2011年11月 [査読有り][通常論文]
   

  Conjugated fatty acids (CFA) have received increased interest because of their beneficial effects on human health, including preventing cancer development. Conjugated linoleic acids (CLA) are such CFA, and have been reviewed extensively for their multiple biological activities. In contrast to other types of CFAs including CLA that are found at low concentrations (less than 1%) in natural products, conjugated linolenic acids (CLN) are the only CFAs that occur in higher quantities in natural products. Some plant seeds contain a considerably high concentration of CLN (30 to 70 wt% lipid). Our research group has screened CLN from different plant seed oils to determine their cancer chemopreventive ability. This review describes the physiological functions of CLN isomers that occur in certain plant seeds. CLN are able to induce apoptosis through decrease of Bcl-2 protein in certain human cancer cell lines, increase expression of peroxisome proliferator-activated receptor (PPAR)-gamma, and up-regulate gene expression of p53. Findings in our preclinical animal studies have indicated that feeding with CLN resulted in inhibition of colorectal tumorigenesis through modulation of apoptosis and expression of PPAR gamma and p53. In this review, we summarize chemopreventive efficacy of CLN against cancer development, especially colorectal cancer.
• The effect of milk polar lipids separated from butter serum on the lipid levels in the liver and the plasma of obese-model mouse (KK-A(y))

  Shiomi Watanabe, Tomoki Takahashi, Leo Tanaka, Yuko Haruta, Makoto Shiota, Masashi Hosokawa, Kazuo Miyashita

  JOURNAL OF FUNCTIONAL FOODS 3 4 313 - 320 2011年10月 [査読有り][通常論文]
   

  The effect of lipid concentrated-butter serum (LC-BS) on the plasma and hepatic cholesterol and triacylglycerol levels of obese-model mouse (KK-A(Y)) was evaluated. The same analysis was done on the main lipid fractions from LC-BS, namely, ceramide rich fraction (Ceramide-fr), phosphatidylethanolamine (PE) rich fraction (PE-fr), and sphingomyelin (SPM) rich fraction (SPM-fr). Plasma cholesterol of mice fed LC-BS and Ceramide-fr was significantly (P < 0.05) lower than that of the control. Hepatic total cholesterol and triacylglycerol levels was also reduced significantly by Ceramide-fr feeding (P < 0.05). Although there was no significant difference in the fatty acid composition of all dietary lipids, significant decrease (P < 0.05) in content of 18:1n-9 was found in the liver lipids of the mice fed Ceramide-fr containing diet. The level of 16:1n-7 and 18:1n-7 was also reduced by Ceramide-fr feeding. This result suggests the down-regulation of stearoyl-CoA desaturase-1 (SCD1) by milk ceramides, which would be related to the decrease in triacylglycerol and cholesterol levels in the liver and in the plasma. (C) 2011 Elsevier Ltd. All rights reserved.
• Nitrocapsanthin and Nitrofucoxanthin, Respective Products of Capsanthin and Fucoxanthin Reaction with Peroxynitrite

  Makoto Tsuboi, Hideo Etoh, Kyuki Kato, Hiroki Nakatugawa, Hideki Kato, Yasunori Maejima, Gaku Matsumoto, Hironobu Mori, Masashi Hosokawa, Kazuo Miyashita, Harukuni Tokuda, Nobukuni Suzuki, Takashi Maoka

  JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 59 19 10572 - 10578 2011年10月 [査読有り][通常論文]
   

  The in vitro reactivity of capsanthin (1) and fucoxanthin (2) with peroxynitrite was investigated, and the reaction products produced by scavenging with peroxynitrite were analyzed. (14'Z)-Nitrocapsanthin (3) and 12-nitrocapsanthin (4) were isolated from the products of the reaction of capsanthin with peroxynitrite. Similarly, (14Z)-15-nitrofucoxanthin (5), (11Z)-11-nitrofucoxanthin (6), and (14Z,9'Z)-15-nitrofucoxanthin (7) were obtained from the reaction of peroxynitrite reaction with fucoxanthin. Capsanthin and fucoxanthin inhibited the nitration of tyrosine by peroxynitrite. Furthermore, nitrocapsanthins (3 and 4) and nitrofucoxanthins (5 and 6) exhibited an inhibitory effect on Epstein Barr virus early antigen activation in Raji cells and an antiproliferative effect on human pancreatic carcinoma. Moreover, nitrocapsanthins (3 and 4) inhibited carcinogensis of mouse skin tumors initiated by 7,12-dimethylbenz[a]anthracene (DMBN).
• Dietary astaxanthin inhibits colitis and colitis-associated colon carcinogenesis in mice via modulation of the inflammatory cytokines

  Yumiko Yasui, Masashi Hosokawa, Nana Mikami, Kazuo Miyashita, Takuji Tanaka

  CHEMICO-BIOLOGICAL INTERACTIONS 193 1 79 - 87 2011年08月 [査読有り][通常論文]
   

  Astaxanthin (AX) is one of the marine carotenoid pigments, which possess powerful biological antioxidant, anti-inflammatory and anti-cancer properties. The purpose of this study is to investigate possible inhibitory effect of AX against inflammation-related mouse colon carcinogenesis and dextran sulfate sodium (DSS)-induced colitis in male ICR mice. We conducted two different experiments. In the first experiment, we evaluated the effects of AX at three dose levels, 50, 100 and 200 ppm in diet, on colitis-associated colon carcinogenesis induced by azoxymethane (AOM)/DSS in mice. In the second, the effects of the AX (10(1 and 200 ppm) in diet on DSS-induced colitis were determined. We found that dietary AX significantly inhibited the occurrence of colonic mucosal ulcers, dysplastic crypts, and colonic adenocarcinoma at week 20. AX-feeding suppressed expression of inflammatory cytokines, including nuclear factor (NF)-kappa B, tumor necrosis factor (TINIF)-alpha and interleukin (IL)-1 beta, inhibited proliferation, and induced apoptosis in the colonic adenocarcinomas. Feeding with 200 ppm AX, but not 100 ppm, significantly inhibited the development of DSS-induced colitis. AX feeding (200 ppm in diet) also lowered the protein expression of NF-kappa B, and the mRNA expression of inflammatory cytokines, including IL-1 beta, IL-6, and cyclooxygenase (COX)-2. Our results suggest that the dietary AX suppresses the colitis and colitis-related colon carcinogenesis in mice, partly through inhibition of the expression of inflammatory cytokine and proliferation. Our findings suggest that AX is one of the candidates for prevention of colitis and inflammation-associated colon carcinogenesis in humans. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
• The allenic carotenoid fucoxanthin, a novel marine nutraceutical from brown seaweeds

  Kazuo Miyashita, Sho Nishikawa, Fumiaki Beppu, Takayuki Tsukui, Masayuki Abe, Andmasashi Hosokawa

  JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE 91 7 1166 - 1174 2011年05月 [査読有り][通常論文]
   

  Obesity and type 2 diabetes are pathologies with rapidly growing prevalence throughout the world. A few molecular targets offer the mosthope for anti-obesity and anti-diabetic therapeutics. One of the keys to success will be the induction of uncoupling protein 1 (UCP1) in abdominal white adipose tissue (WAT) and the regulation of cytokine secretions from both abdominal adipose cells and macrophage cells infiltrated into adipose tissue. Anti-obesity and anti-diabetic effects of fucoxanthin, a characteristic carotenoid found in brown seaweeds, have been reported. Nutrigenomic studies reveal that fucoxanthin induces UCP1 in abdominal WAT mitochondria, leading to the oxidation of fatty acids and heat production in WAT. Fucoxanthin improves insulin resistance and decreases blood glucose levels through the regulation of cytokine secretions from WAT. The key structure of carotenoids for the expression of anti-obesity effect is suggested to be the carotenoid end of the polyene chromophore, which contains an allenic bond and two hydroxyl groups. (C) 2011 Society of Chemical Industry
• Effect of Brown Seaweed Lipids on Fatty Acid Composition and Lipid Hydroperoxide Levels of Mouse Liver

  M. K. Widjaja-Adhi Airanthi, Naoya Sasaki, Sayaka Iwasaki, Nobuko Baba, Masayuki Abe, Masashi Hosokawa, Kazuo Miyashita

  JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 59 8 4156 - 4163 2011年04月 [査読有り][通常論文]
   

  Brown seaweed lipids from Undaria pinnahfida (Wakame), Sargassum horneri (Akamoku), and Cystoseira hakodatensis (Uganomoku) contained several bioactive compounds, namely, fucoxanthin, polyphenols, and omega-3 polyunsaturated fatty acids (PUPA). Fucoxanthin and polyphenol contents of Akamoku and Uganomoku lipids were higher than those of Wakame lipids, while Wakame lipids showed higher total omega-3 PUFA content than Akamoku and Uganomolcu lipids. The levels of docosahexaenoic acid (DHA) and arachidonic acid (AA) in liver lipids of KK-A(y) mouse significantly increased by Akamoku and Uganomoku lipid feeding as compared with the control, but not by Wakame lipid feeding. Fucoxanthin has been reported to accelerate the bioconversion of omega-3 PUFA and omega-6 PUPA to DHA and AA, respectively. The higher hepatic DHA and AA level of mice fed Akamoku and Uganomoku lipids would be attributed to the higher content of fucoxanthin of Akamoku and Uganomoku lipids. The lipid hydroperoxide levels of the liver of mice fed brown seaweed lipids were significantly lower than those of control mice, even though total PUFA content was higher in the liver of mice fed brown seaweed lipids. This would be, at least in part, due to the antioxidant activity of fucoxanthin metabolites in the liver.
• Suppressive Effects of Amarouciaxanthin A on 3T3-L1 Adipocyte Differentiation through Down-regulation of PPAR gamma and C/EBP alpha mRNA Expression

  Mi-Jin Yim, Masashi Hosokawa, Yoshiyuki Mizushina, Hiromi Yoshida, Yasunori Saito, Kazuo Miyashita

  JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 59 5 1646 - 1652 2011年03月 [査読有り][通常論文]
   

  Fucoxanthin is converted to fucoxanthinol and amarouciaxanthin A in mice. It was previously reported that fucoxanthinol attenuated the adipogenesis of 3T3-L1 cells. However, the effects of amarouciaxanthin A on adipocyte differentiation have not been clarified. This study examined the effects of amarouciaxanthin A on 3T3-L1 adipogenesis by comparing the effects of fucoxanthinol, isofucoxanthinol, and amarouciaxanthin B. Amarouciaxanthin A significantly decreased glycerol-3-phosphate dehydrogenase (GPDH) activity, which was measured as an indicator of adipocyte differentiation. The suppressive effect of amarouciaxanthin A was stronger than that of fucoxanthinol, amarouciaxanthin B, and isofucoxanthinol. The mRNA expressions of adipocyte fatty acid-binding protein (aP2), lipoprotein lipase (LPL), and glucose-transporter 4 (Glut4) in 3T3-L1 cells were markedly down-regulated by amarouciaxanthin A compared to fucoxanthinol. Furthermore, the expression levels of peroxisome proliferator-activated receptor gamma (PPAR gamma) and CCAAT-enhancer-binding protein alpha (C/EBP alpha) which are the key adipogenic transcriptional factors, were also de creased by amarouciaxanthin A during adipocyte differentiation. These results show that amarouciaxanthin A, which is a dominant metabolite of fucoxanthin in white adipose tissue, suppressed 3T3-L1 adipocyte differentiation.
• Synthesis of novel phospholipids that bind phenylalkanols and hydroquinone via phospholipase D-catalyzed transphosphatidylation

  Yukihiro Yamamoto, Hideyuki Kurihara, Kazuo Miyashita, Masashi Hosokawa

  NEW BIOTECHNOLOGY 28 1 1 - 6 2011年01月 [査読有り][通常論文]
   

  Phenylalkanols such as tyrosol and hydroxytyrosol (h-tyrosol), which possess antioxidant and anticancer properties, were phosphatidylated by phospholipase D (PLD)-catalyzed transphosphatidylation. After a 24-hour reaction of phosphatidylcholine (PC) and tyrosol with PLD, a new product was detected by TLC and identified to phosphatidyl-tyrosol by high-resolution MS and NMR analyses. The optimum reaction conditions were as follows: soyPC 50 mu mol, tyrosol 500 mu mol, ethyl acetate 1.6 ml, PLD 1.6 U, 0.2 M sodium acetate buffer (pH 5.6) 0.8 ml, 37 degrees C for 24 hours. Under the optimum reaction conditions, the yields of phosphatidyl-tyrosol, hydroquinone (HQ), 2-(4-aminophenyl) ethanol (4APE), h-tyrosol and 2-phenylethanol (PEA) were 87 +/- 3.7, 13 +/- 1.3, 90 +/- 2.3, 64 +/- 5.5 and 85 +/- 1.0 mol%, respectively. Furthermore, from the results of transphosphatidylation of soyPC with several phenylethanols and phenylpropanols, we established the following details about the reaction specificity of transphosphatidylation by PLD from Streptomyces sp.: (1) para-amino and para-hydroxyl groups in the benzene ring of PEA derivatives do not affect the transphosphatidylation by PLD, whereas meta-hydroxyl group slightly inhibits the transphosphatidylation. (2) Meta- and ortho-methyl groups in the benzene ring of PEA derivatives also slightly inhibit the transphosphatidylation. (3) Secondary and tertiary alcohols and hydroquinone are difficult to transphosphatidylate by PLD.
• Comparative Antioxidant Activity of Edible Japanese Brown Seaweeds

  M. K. Widjaja-Adhi Airanthi, Masashi Hosokawa, Kazuo Miyashita

  JOURNAL OF FOOD SCIENCE 76 1 C104 - C111 2011年01月 [査読有り][通常論文]
   

  Japanese edible brown seaweeds, Eisenia bicyclis (Arame), Kjellmaniella crassifolia (Gagome), Alaria crassifolia (Chigaiso), Sargassum horneri (Akamoku), and Cystoseira hakodatensis (Uganomoku) were assayed for total phenolic content (TPC), fucoxanthin content, radical scavenging activities (DPPH, peroxyl radical, ABTS, and nitric oxide), and antioxidant activity in a liposome system. Among the solvents used for extraction, methanol was the most effective to extract total phenolics (TPC) from brown seaweeds. Among 5 kinds of brown seaweeds analyzed, methanol extract from C. hakodatensis was the best source for antioxidants. The high antioxidant activity of the extract was based not only on the high content of phenolics, but on the presence of fucoxanthin. No significant correlation (P > 0.05) was observed between TPC per gram extract with DPPH radical scavenging activity of the methanol extracts. These observed discrepancy would be due to structural variations in the phenolic compounds, and different levels of fucoxanthin in the extracts. The present study also demonstrated the synergy in the antioxidant activity of the combination of brown seaweed phenolics and fucoxanthin.
• Antiobesity Effects of Undaria Lipid Capsules Prepared with Scallop Phospholipids

  Tomoko Okada, Yasuyuki Mizuno, Shinichi Sibayama, Masashi Hosokawa, Kazuo Miyashita

  JOURNAL OF FOOD SCIENCE 76 1 H2 - H6 2011年01月 [査読有り][通常論文]
   

  Based on previous research findings, a capsule was developed containing n-3 polyunsaturated fatty acid rich scallop phospholipids (PLs) with an incorporation of brown seaweed (Undaria pinnatifida) lipids (ULs) containing fucoxanthin. The antiobesity effects of the capsules were evaluated with an animal model using 3-wk-old male KK-A(y) mice. Each group received different combinations of lipid (UL, PL, UL + PL, or UL + PL capsule) either incorporated into the diet or into drinking water. Animals were sacrificed after a 4-wk experimental feeding period, and adipose tissues and organs were dissected and weighed. Blood samples were obtained to determine plasma lipid profiles. Uncoupling protein 1 (UCP1) mRNA expression levels were determined by real-time polymerase chain reaction analysis, and UCP1 expression was determined by western blotting analysis. Treatment with either UL alone or UL + PL (capsule) through drinking water resulted in a significant reduction in body weight, compared to the control group. The total white adipose tissue weight of mice fed the UL + PL capsule in drinking water was significantly reduced. Both UCP1 and UCP1 mRNA expression in epididymal fat from mice fed the capsule were significantly higher than in the control group. These results suggest that incorporation of UL into scallop-derived PL by means of capsulation may lead to an additive increase in the antiobesity properties of these bioactive lipids.
• Fucoxanthin regulates adipocytokine mRNA expression in white adipose tissue of diabetic/obese KK-A(y) mice

  Masashi Hosokawa, Tatsuya Miyashita, Sho Nishikawa, Shingo Emi, TakaYuki Tsukui, Fumiaki Beppu, Tomoko Okada, Kazuo Miyashita

  ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS 504 1 17 - 25 2010年12月 [査読有り][通常論文]
   

  Fucoxanthin, a marine carotenoid found in edible brown seaweeds, attenuates white adipose tissue (WAT) weight gain and hyperglycemia in diabetic/obese KK-A(y) mice, although it does not affect these parameters in lean C57BL/6J mice. In perigonadal and mesenteric WATs of KK-A(y) mice fed fucoxanthin, mRNA expression levels of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-a (TNF-alpha), which are considered to induce insulin resistance, were markedly reduced compared to control mice. In contrast to KK-A(y) mice, fucoxanthin did not alter MCP-1 and TNF-a mRNA expression levels in the WAT of lean C57BL/6J mice. Interleukin-6 (IL-6) and plasminogen activator inhibitor-1 mRNA expression levels in WAT were also decreased by fucoxanthin in KK-A(y) mice. In differentiating 3T3-F442A adipocytes, fucoxanthinol, which is a fucoxanthin metabolite found in WAT, attenuated TNF-alpha-induced MCP-1 and IL-6 mRNA overexpression and protein secretion into the culture medium. In addition, fucoxanthinol decreased TNF-a, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) mRNA expression in RAW264.7 macrophage-like cells stimulated by palmitic acid. These findings indicate that fucoxanthin regulates mRNA expression of inflammatory adipocytokines involved in insulin resistance, iNOS, and COX-2 in WAT and has specific effects on diabetic/obese KK-A(y) mice, but not on lean C57BL/6J mice. (C) 2010 Elsevier Inc. All rights reserved.
• Anti-obesity and anti-diabetic effects of allenic carotenoid, fucoxanthin

  Kazuo Miyashita, Hayato Maeda, Tomoko Okada, Masayuki Abe, Masashi Hosokawa

  AGRO FOOD INDUSTRY HI-TECH 21 6 24 - 27 2010年11月 [査読無し][通常論文]
   

  Fucoxanthin, a characteristic carotenoid found in brown seaweeds, shows anti-obesity and anti-diabetic effects on the basis of specific molecular mechanism. Fucoxanthin induces uncoupling protein 1 expression in white adipose tissue (WAT) mitochondria leading to oxidation of fatty acids and heat production in WAT. Fucoxanthin improves insulin resistance and decreases blood glucose level through the down-regulation of adipokines such as TNF alpha, MCP-1, IL-6, and PAI-1 in WAT and up-regulation of glucose transporter 4 (GLUT4) in skeletal muscle. The anti-obesity effect of fucoxanthin is likely linked to its structural characteristic - an allene bond and an additional hydroxyl substituent on the side group of the fucoxanthin metabolites, fucoxanthinol and amarouciaxanthin A.
• Value Addition to Seafood Processing Discards

  Sachindra M. Nakkarike, Bhaskar Narayan, Masashi Hosokawa, Kazuo Miyashita

  Handbook of Seafood Quality, Safety and Health Applications 390 - 401 2010年09月02日 [査読無し][通常論文]
  
• Purified Canola Lutein Selectively Inhibits Specific Isoforms of Mammalian DNA Polymerases and Reduces Inflammatory Response

  Sho Horie, Chiaki Okuda, Takatoshi Yamashita, Kenichi Watanabe, Kouji Kuramochi, Masashi Hosokawa, Toshifumi Takeuchi, Makiko Kakuda, Kazuo Miyashita, Fumio Sugawara, Hiromi Yoshida, Yoshiyuki Mizushina

  LIPIDS 45 8 713 - 721 2010年08月 [査読有り][通常論文]
   

  In the screening of DNA polymerase (pol) inhibitor, we isolated lutein, a carotenoid, from the crude (unrefined) pressed oil of canola (low erucic acid rapeseed, Brassica napus L.). Commercially prepared carotenoids such as lutein (1), zeaxanthin (2), beta-cryptoxanthin (3), astaxanthin (4), canthaxanthin (5), beta-carotene (6), lycopene (7), capsanthin (8), fucoxanthin (9) and fucoxanthinol (10), were investigated for the inhibitory activities of pols. Compounds 1, 2 and 8 exhibited strong inhibition of the activities of mammalian pols beta and lambda, which are DNA repair- and/or recombination-related pols. On the other hand, all carotenoids tested had no influence on the activity of a mammalian pol alpha, which is a DNA replicative pol. Lutein (1) was the strongest pol inhibitor of mammalian pols beta and lambda in the prepared ten carotenoids tested, but did not influence of the activities of mammalian pols alpha, gamma, delta and epsilon. The tendency for pols beta and lambda inhibition by these carotenoids showed a positive correlation with the suppression of TPA (12-O-tetradecanoylphorbol-13-acetate)-induced inflammation. These results suggest that cold pressed unrefined canola/rapeseed oil, or other oils with high levels of lutein and other carotenoids, may be useful for their anti-inflammatory properties.
• Brown Sea Weed Lipids as Possible Source for Nutraceuticals and Functional Foods

  M. Airanthi K. Widjaja-Adhi, Takayuki Tsukui, Masashi Hosokawa, Kazuo Miysahita

  Biocatalysis and Biomolecular Engineering 211 - 223 2010年07月19日 [査読有り][通常論文]
  
• Suppressive effects of the marine carotenoids, fucoxanthin and fucoxanthinol on triglyceride absorption in lymph duct-cannulated rats

  Megumi Matsumoto, Masashi Hosokawa, Noriko Matsukawa, Masahito Hagio, Aki Shinoki, Megumi Nishimukai, Kazuo Miyashita, Takaji Yajima, Hiroshi Hara

  EUROPEAN JOURNAL OF NUTRITION 49 4 243 - 249 2010年06月 [査読有り][通常論文]
   

  Fucoxanthin isolated from edible seaweeds and its metabolite fucoxanthinol have been recently found to have anti-obesity effects, but the mechanism is not fully understood.We investigated the effects of these carotenoids on the absorption of triglycerides in conscious rats implanted with cannulae into a lymph duct and the portal or jugular vein.A duodenal infusion of 1 ml of test oil emulsion with or without 2 mg of fucoxanthin or fucoxanthinol was administered in the lymph duct and the portal (Experiment 1) or the jugular vein (Experiment 2) cannulated rats. The test oil contained 10% soybean oil (Experiment 1) and pre-digested 10% soybean oil (Experiment 2). The inhibitory activities of these carotenoids on pancreatic lipase activity were measured in vitro.Increases in lymphatic and blood triglyceride levels were much lower in the two carotenoid-treated groups than in the carotenoid-free group, indicating that these carotenoids inhibit triglyceride absorption. The total amounts of triglycerides released into the lymph after 4 h in the carotenoid-free, fucoxanthin and fucoxanthinol groups were 113.5, 59.4 and 53.1 mu mol, respectively. The inhibitory effects of carotenoids were completely abolished after an infusion of pre-digested soybean oil containing carotenoids. Furthermore, these carotenoids inhibited pancreatic lipase activity in vitro. Regarding absorptive route, we found that fucoxanthinol, but not fucoxanthin, appeared in lymph fluid, whereas neither carotenoid was detected in portal blood.These results show that these two marine carotenoids inhibit lipase activity in the gastrointestinal lumen and suppress triglyceride absorption, and fucoxanthin was converted to fucoxanthinol in the intestine and released into the lymph.
• Effects of sea squirt (Halocynthia roretzi) lipids on white adipose tissue weight and blood glucose in diabetic/obese KK-A(y) mice

  Nana Mikami, Masashi Hosokawa, Kazuo Miyashita

  MOLECULAR MEDICINE REPORTS 3 3 449 - 453 2010年05月 [査読有り][通常論文]
   

  Lipids extracted from Halocynthia roretzi contain n-3 polyunsaturated fatty acids such as eicosapentaenoic acid and docosahexaenoic acid, as well as carotenoids. The aim of the present study was to evaluate the effect of H. roretzi lipids on white adipose tissue (WAT) weight and high blood glucose levels in diabetic/obese KK-A(y) mice. H. roretzi lipids were fed to the diabetic/obese KK-A(y) mice for 5 weeks. In the mice treated with the H. roretzi lipids compared to control mice, WAT weight was reduced, blood glucose levels and leptin mRNA expression in the epididymal WAT were significantly decreased, serum leptin levels also tended to decrease, and serum adiponectin levels tended to increase. These results demonstrate that H. roretzi lipids have beneficial health effects on diabetic/obese KK-A(y) mice.
• Radical scavenging and singlet oxygen quenching activity of extracts from Indian seaweeds

  N. M. Sachindra, M. K. W. A. Airanthi, M. Hosokawa, K. Miyashita

  JOURNAL OF FOOD SCIENCE AND TECHNOLOGY-MYSORE 47 1 94 - 99 2010年01月 [査読有り][通常論文]
   

  Free radicals and singlet oxygen are responsible for oxidative stress related diseases and many natural compounds are known to have antioxidant properties. In this study, extracts from brown and red seaweeds of Indian origin were evaluated for their ability to scavenge different radicals and quench singlet oxygen. The crude extract in methanol and its fractions in different solvents were evaluated for their activity. The methanol extract and its fractions from brown seaweed exhibited higher 2,2'-azinobis(3-ethyl-benzothizoline-6-sulfonic acid) radical scavenging activity with more than 90% scavenging in butanol and ethyl acetate fractions and correlated with polyphenol content. There was a significant difference (p <= 0.001) in hydroxyl radical scavenging activity between different fractions of the same seaweed. Among the crude extracts, extract from Gracilaria corticata showed the highest (14.0%) activity. Crude extract from brown seaweeds showed higher peroxyl radical scavenging activity compared to red seaweeds. In fractions from brown seaweed extracts, highest activity was observed in ethyl acetate fraction (>88%) followed by hexane fraction (>40%). Ethyl acetate fraction from crude extract showed higher inhibitory activity against hemoglobin induced linoleic acid oxidation. Singlet oxygen quenching activity of the crude extract from brown seaweed was lower (<13%) compared to red seaweeds (16.4-20.5%).
• In vitro and in vivo evaluation of mutagenicity of fucoxanthin (FX) and its metabolite fucoxanthinol (FXOH)

  Fumiaki Beppu, Yoshimi Niwano, Emiko Sato, Masahiro Kohno, Takayuki Tsukui, Masashi Hosokawa, Kazuo Miyashita

  JOURNAL OF TOXICOLOGICAL SCIENCES 34 6 693 - 698 2009年12月 [査読有り][通常論文]
   

  Mutagenicity of fucoxanthinol (FXOH), the major compound after oral ingestion of fucoxanthin (FX), was evaluated by in vitro Ames test, and of FX by in vivo micronucleus test. In in vitro Ames test, bacterial reverse mutation was examined by using Salmonella typhimurium strains TA98, TA100. TA1535 and TA1537, and Escherichia coli Wp2uvrA/pKM101, with or without metabolic activation by S9 mix in the preincubation method, and mutagenicity of FXOH was found to be negative in all cases. In in vivo micronucleus test, mice were orally administered with FX at doses of 500, 1,000 and 2,000 mg/kg, and the bone marrow cells were taken 24 hr after the administration to observe the incidence of micronucleus cells, and mutagenicity of FX was found to be negative at all doses. Based on the data of the present Study it can be presumed that orally administered FX is a safe compound in terms of mutagenicity under the experimental conditions employed here.
• Inhibition of proliferation of a hepatoma cell line by fucoxanthin in relation to cell cycle arrest and enhanced gap junctional intercellular communication

  Cheng-Ling Liu, Yung-Sheng Huang, Masashi Hosokawa, Kazuo Miyashita, Miao-Lin Hu

  CHEMICO-BIOLOGICAL INTERACTIONS 182 2-3 165 - 172 2009年12月 [査読有り][通常論文]
   

  Fucoxanthin is one of the most abundant carotenoids found in Undaria pinnatifida and has been shown to inhibit tumor proliferation in vitro. However, the mechanisms underlying the anti-cancer effects of fucoxanthin are unclear. In this study, we hypothesized that fucoxanthin may cause cell cycle arrest and enhance gap junctional intercellular communication (GJIC) in SK-Hep-1 human hepatoma cells. Data revealed that fucoxanthin (1-20 mu M) strongly and concentration-dependently inhibited the proliferation of SK-Hep-1 cells at 24 h of incubation, whereas fucoxanthin facilitated the growth of a murine embryonic hepatic (BNL CL2) cells at 24 h of incubation and only slightly slowed the cell proliferation at 48 h. In SK-Hep-1 cells, fucoxanthin caused cell cycle arrest at G0/G1 phase and induced cell apoptosis, as evidenced by increased subG1 cells and induction of DNA strand breaks. Using scrape loading-dye-transfer assay, fucoxanthin was found to significantly enhance GJIC of SK-Hep-1 cells without affecting that of BNL CL2 cells. In addition, fucoxanthin significantly increased protein and mRNA expressions of connexin 43 (Cx43) and connexin 32 (Cx32) in SK-Hep-1 cells. Moreover, fucoxanthin markedly increased the concentration of intracellular calcium levels in SK-Hep-1 cells. Thus, fucoxanthin is specifically antiproliferative against SK-Hep-1 cells, and the effect is associated with upregulation of Cx32 and Cx43, which enhances GJIC of SK-Hep-1 cells. The enhanced GJIC may be responsible for the increase of the intracellular calcium level, which then causes cell cycle arrest and apoptosis. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
• Effect of Marine Protein Supplementation on Lipid Profile of Growing Rats Compared to Soybean Protein and Casein

  Bhasakar Narayan, Kohei Yamaguchi, Masashi Hosokawa, Kenji Fukunaga, Toshimasa Nishiyama, Kazuo Miyashita

  FOOD SCIENCE AND BIOTECHNOLOGY 18 6 1330 - 1335 2009年12月 [査読有り][通常論文]
   

  Although beneficial effects of dietary plant proteins on lipid metabolism are well documented, not much information exists on the influence of different seafood proteins on the lipid metabolism. The present study evaluated the effect of 2 marine proteins (tuna protein and scallop ovary proteins) in comparison to casein and soy protein in male Wistar rats. The concentration of total lipids in the plasma of rats fed experimental diets was significantly lower from that of control (278.2 mg/dL) group (p<0.05); and, the liver lipid content was not significantly different (p>0.05). Fecal excretion of cholesterol and bile acids was significantly higher in marine proteins and soy protein fed groups compared to casein only fed control (6.1 and 6.4 mg/day, respectively) group (p<0.05). No significant differences were observed in the mRNA concentrations of different transcriptional factors (p>0.05).
• Anti-obesity and anti-diabetic effects of fucoxanthin on diet-induced obesity conditions in a murine model

  Hayato Maeda, Masashi Hosokawa, Tokutake Sashima, Katsura Murakami-Funayama, Kazuo Miyashita

  MOLECULAR MEDICINE REPORTS 2 6 897 - 902 2009年11月 [査読有り][通常論文]
   

  Fucoxanthin, a characteristic carotenoid of brown algae, has been reported to exert an anti-diabetic effect in an obese murine model. Wakame (Undaria pinnatifida), an edible seaweed, is rich in fucoxanthin. This study examined the anti-obesity and anti-diabetic effects of fucoxanthin-rich wakame lipids (WLs) on high fat (HF) diet-induced obesity in mice. Mice were fed a high fat control (HFC) or normal fat control (NFC) diet for 10 weeks. The HF diet-fed group was administered a HF diet containing WLs for a further 5 weeks. Parameters related to diabetes and obesity conditions were evaluated and compared. The HF-WL diet, which was rich in fucoxanthin, significantly suppressed body weight and white adipose tissue (WAT) weight gain induced by the HF diet. Dietary administration of the HF diet resulted in hyperglycemia, hyperinsulinemia and hyperleptinemia in the mouse model. These perturbations were completely normalized in the HF-WL diet-fed group. Increased expression of monocyte chemoattractant protein-1 (MCP-1) mRNA expression was observed in HFC mice, but was normalized in the HF-WL groups. Moreover, the HF-WL diet promoted mRNA expression of beta 3-adrenergic receptor (Adrb3) in WAT and glucose transporter 4 (GLUT4) mRNA in skeletal muscle tissues. These results suggest that dietary WLs may ameliorate alterations in lipid metabolism and insulin resistance induced by a HF diet. There is therefore a biochemical and nutritional basis for the application of fucoxanthin-rich WLs as a functional food to prevent obesity and diabetes-related disorders.
• Single and repeated oral dose toxicity study of fucoxanthin (FX), a marine carotenoid, in mice

  Fumiaki Beppu, Yoshimi Niwano, Takayuki Tsukui, Masashi Hosokawa, Kazuo Miyashita

  JOURNAL OF TOXICOLOGICAL SCIENCES 34 5 501 - 510 2009年10月 [査読有り][通常論文]
   

  Fucoxanthin (FX), a xanthophyll derivative, is ail orange-colored pigment present in edible brown algae. As a part of safety evaluation, single and repeated oral dose toxicity study of FX was conducted. In a single dose study, FX purified from seaweed was orally administered to male and female ICR mice at doses of 1,000 and 2,000 mg/kg. In a repeated doses study, FX at doses of 500 and 1,000 mg/kg was orally administered for 30 days. In both studies, no mortality and no abnormalities in gross appearance were observed. In the repeated doses Study, histological observation revealed no abnormal changes in liver, kidney, spleen and gonadal tissues of any of the FX-treated groups. However, significantly increased total cholesterol concentrations were shown by plasma biochemical analyses in all FX-treated groups. Although total bilirubin concentrations were increased by FX, it was established that presence of fucoxanthinol, a major metabolite of FX, interfered with bilirubin determination in plasma. To further ascertain the safety of FX, the mechanism by which FX induces hypercholesterolemia in mice and species differences in the induction of hypercholesterolemia should be elucidated.
• EVALUATION OF RECOVERABLE FUNCTIONAL LIPID COMPONENTS OF SEVERAL BROWN SEAWEEDS (PHAEOPHYTA) FROM JAPAN WITH SPECIAL REFERENCE TO FUCOXANTHIN AND FUCOSTEROL CONTENTS

  Masaru Terasaki, Atsushi Hirose, Bhaskar Narayan, Yuta Baba, Chikara Kawagoe, Hajime Yasui, Naotsune Saga, Masashi Hosokawa, Kazuo Miyashita

  JOURNAL OF PHYCOLOGY 45 4 974 - 980 2009年08月 [査読有り][通常論文]
   

  Fucoxanthin (Fx) and fucosterol (Fs) are characteristic lipid components of brown seaweeds that afford several health benefits to humans. This article describes the quantitative evaluation of lipids of 15 species of brown seaweeds with specific reference to Fx, Fs, and functional long-chain omega-6/omega-3 polyunsaturated fatty acids (PUFAs). In addition, fatty-acid composition of selected species was also accomplished in the study. Major omega-3 PUFAs in the brown seaweeds analyzed were alpha-linolenic acid (18:3n-3), octadecatetraenoic acid (18:4n-3), arachidonic acid (20:4n-6), and eicosapentaenoic acid (20:5n-3). Both Fx (mg center dot g(-1) dry weight [dwt]) and Fs (mg center dot g(-1) dwt) were determined to be relatively abundant in Sargassum horneri (Turner) C. Agardh (Fx, 3.7 +/- 1.6; Fs, 13.4 +/- 4.4) and Cystoseira hakodatensis (Yendo) Fensholt (Fx, 2.4 +/- 0.9; Fs, 8.9 +/- 2.0), as compared with other brown seaweed species. Studies related to seasonal variation in Fx, Fs, and total lipids of six brown algae [S. horneri, C. hakodatensis, Sargassum fusiforme (Harv.) Setch., Sargassum thunbergii (Mertens ex Roth) Kuntze, Analipus japonicus (Harv.) M. J. Wynne, and Melanosiphon intestinalis (D. A. Saunders) M. J. Wynne] indicated that these functional lipid components reached maximum during the period between January and March. The functional lipid components present in these seaweeds have the potential for application as nutraceuticals and novel functional ingredients after their recovery.
• Edible Japanese seaweed, wakame (Undaria pinnatifida) as an ingredient in pasta: Chemical, functional and structural evaluation

  P. Prabhasankar, P. Ganesan, N. Bhaskar, A. Hirose, Nimishmol Stephen, Lalitha R. Gowda, M. Hosokawa, K. Miyashita

  FOOD CHEMISTRY 115 2 501 - 508 2009年07月 [査読有り][通常論文]
   

  Wakame (Undaria pinnatifida) is edible seaweed rich in fucoxanthin; whilst, pasta is an important dish from nutritional and gastronomic point of view. Pasta was prepared with wakame as an ingredient at different levels. In vitro antioxidant properties, total phenolic content, fatty acid composition, fucoxanthin and fucosterol contents formed the major bio-functional characteristics analysed. Pasta with 10% wakame was acceptable sensorially. The total phenolic content varied between 0.10 and 0.94 mg gallic acid equivalents (GAE)/g, whilst total antioxidant activity varied from 0.16 to 2.14 mg ascorbic acid equivalents (AAE)/g, amongst different samples. 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and superoxide radical scavenging activities of sensorily acceptable pasta were 7.71% and 4.56%, respectively. The sensorily acceptable pasta had a mild seaweed flavour with taste similar to control pasta, as assessed by panelists. The ratio of n-3 to n-6 fatty acid in seaweed incorporated pasta was 1:3.4 as compared to 1:15.2 in the control. Heat process involved in pasta preparation and cooking did not destroy fucoxanthin. Microstructure studies revealed the enhanced interaction between starch granules and protein matrix in pasta containing seaweeds up to 20%. (C) 2008 Elsevier Ltd. All rights reserved.
• Antiobesity Effect of Allenic Carotenoid, Fucoxanthin

  Kazuo Miyashita, Masashi Hosokawa

  Nutrigenomics and Proteomics in Health and Disease: Food Factors and Gene Interactions 145 - 160 2009年06月12日 [査読無し][通常論文]
  
• Effect of Droplet Size on the Oxidative Stability of Soybean Oil TAG and Fish Oil TAG in Oil-in-Water Emulsion

  Goki Azuma, Naoko Kimura, Masashi Hosokawa, Kazuo Miyashita

  JOURNAL OF OLEO SCIENCE 58 6 329 - 338 2009年06月 

  The effect of droplet size on the oxidative stability of triacylglycerol (TAG)-in water emulsion was examined. Microchannel (MC) emulsification was used to make monodispersed emulsion of soybean oil TAG and fish oil TAG with different droplet size. The main polyunsaturated fatty acids (PUFA) of soybean oil TAG and fish oil TAG were linoleic acid (LA; 53%) and docosahexaenoic acid (DHA; 37.3%), respectively. Oxidation was induced by the addition of 2,2'-azobis(2-amidinopropane)-dihydrochloride (AAPH) or ferrous ion. The oxidative stability was followed by the decrease in the oxygen consumption in the solution, peroxide formation, and decrease in the unoxidized PUFA during oxidation, indicating that the oxidative stability of fish oil TAG increased with decreasing the droplet size, while the reverse effect of the droplet size was observed on the oxidation of soybean oil TAG. The decrease in the droplet size induces the increase in the droplet interface, from which the oxidation proceeds to the oil droplet interior. DHA in fish oil TAG would take highly protective interface against oxidative attack of free radicals and metal ions, whereas LA in soybean oil TAG would be more easily oxidized at the interface because of its less protective conformation. The reverse effect of the droplet size on fish oil TAG and soybean oil TAG could be explained by the different interface conformation of both TAG.
• Effect of Droplet Size on the Oxidative Stability of Soybean Oil TAG and Fish Oil TAG in Oil-in-Water Emulsion

  Goki Azuma, Naoko Kimura, Masashi Hosokawa, Kazuo Miyashita

  JOURNAL OF OLEO SCIENCE 58 6 329 - 338 2009年06月 [査読有り][通常論文]
   

  The effect of droplet size on the oxidative stability of triacylglycerol (TAG)-in water emulsion was examined. Microchannel (MC) emulsification was used to make monodispersed emulsion of soybean oil TAG and fish oil TAG with different droplet size. The main polyunsaturated fatty acids (PUFA) of soybean oil TAG and fish oil TAG were linoleic acid (LA; 53%) and docosahexaenoic acid (DHA; 37.3%), respectively. Oxidation was induced by the addition of 2,2'-azobis(2-amidinopropane)-dihydrochloride (AAPH) or ferrous ion. The oxidative stability was followed by the decrease in the oxygen consumption in the solution, peroxide formation, and decrease in the unoxidized PUFA during oxidation, indicating that the oxidative stability of fish oil TAG increased with decreasing the droplet size, while the reverse effect of the droplet size was observed on the oxidation of soybean oil TAG. The decrease in the droplet size induces the increase in the droplet interface, from which the oxidation proceeds to the oil droplet interior. DHA in fish oil TAG would take highly protective interface against oxidative attack of free radicals and metal ions, whereas LA in soybean oil TAG would be more easily oxidized at the interface because of its less protective conformation. The reverse effect of the droplet size on fish oil TAG and soybean oil TAG could be explained by the different interface conformation of both TAG.
• Effect of alpha-tocopherol on the synthesis of phosphatidylglycerol catalyzed by phospholipase D in an aqueous system

  Kounosuke Suzuri, Yukihiro Yamamoto, Masashi Hosokawa, Kazuo Miyashita

  BIOTECHNOLOGY LETTERS 31 5 719 - 723 2009年05月 [査読有り][通常論文]
   

  Phosphatidylglycerol (PG) was synthesized from several phosphatidylcholines (PCs) via phospholipase D (PLD)-catalyzed transphosphatidylation in an aqueous system. The yield of PG were 71 and 68 mol% from soybean PC and egg yolk PC, respectively, under the optimum reaction conditions of 50 mu mol PC, 10 mmol glycerol, 3 ml of acetate buffer, 1.6 U PLD, and 30 mu mol CaCl2 at 37A degrees C for 48 h. In case of salmon roe PC with 14.3% eicosapentaenoic acid and 26.8% docosahexaenoic acid, the PG yield increased to 94 mol% by addition of 46 mu mol alpha-tocopherol, although the PG yield was only 10% in absence of alpha-tocopherol.
• Enhancement of hepatic docosahexaenoic acid and arachidonic acid contents in C57BL/6J mice by dietary fucoxanthin

  Takayuki Tsukui, Nobuko Baba, Masashi Hosokawa, Tokutake Sashima, Kazuo Miyashita

  FISHERIES SCIENCE 75 1 261 - 263 2009年02月 [査読有り][通常論文]
  
• Bio-functions of Marine Carotenoids

  Masashi Hosokawa, Tomoko Okada, Nana Mikami, Izumi Konishi, Kazuo Miyashita

  FOOD SCIENCE AND BIOTECHNOLOGY 18 1 1 - 11 2009年02月 [査読有り][通常論文]
   

  Carotenoids being most important pigments among those occurring in nature, have received increased interest owing to their beneficial effects on human health. An effort is made to review marine carotenoids as important bioactive compounds with reference to their presence, chemical, and biofunctional benefits they afford. The potential beneficial effects of marine carotenoids were particularly focused on astaxanthin and fucoxanthin, major marine carotenoids found in marine animals and aquatic plants, respectively. Both carotenoids show strong antioxidant activity which is attributed to quenching singlet oxygen and scavenging free radicals. The potential role of the carotenoids as dietary antioxidants has been suggested as being one of the main mechanism by which they afford their beneficial health effects such as anticancer activity and anti-inflammatory effect. Only recently, antiobesity effect and antidiabetic effect have been noted as specific and novel biofunctions of fucoxanthin. Nutrigenomic study reveals that fucoxanthin induces uncoupling protein 1 (UCP1) expression in white adipose tissue (WAT) mitochondria to lead to oxidation of fatty acids and heat production in WAT. Fucoxanthin improves insulin resistance and decreases blood glucose level, at least in part, through the down-regulation of tumor necrosis factor alpha (TNF alpha) in WAT of animals.
• Comparative evaluation of growth inhibitory effect of stereoisomers of fucoxanthin in human cancer cell lines

  Y. Nakazawa, T. Sashima, M. Hosokawa, K. Miyashita

  JOURNAL OF FUNCTIONAL FOODS 1 1 88 - 97 2009年01月 [査読有り][通常論文]
   

  Inhibitory effects of geometrical isomers of fucoxanthin - characteristic carotenoid of brown seaweeds - on the growth of various cancer cells and on human leukemia (HL-60), colon cancer (Caco-2) and prostate cancer cells (PC-3 and LNCap) were comparatively evaluated. All-trans fucoxanthin was the major geometrical isomer (similar to 88%) found in the fresh brown seaweed (Undaria pinnatifida) apart from a small amount of 13-cis and 13'-cis isomers (similar to 9%). Incubation of the fucoxanthin isomeric mixtures, all-trans fucoxanthin with a small amount of 13-cis and 13'-cis isomers, produced 9'-cis isomer (5%) and increased the contents of 13-cis and 13'-cis isomers (27%). The antiproliferative effect of the mixture of 13-cis and 13'-cis isomers was stronger than all other geometrical isomers evaluated in the study. The inhibition of growth of HL-60 cells was higher in case of 13'-cis isomer followed by 13-cis and all-trans isomers. The potent inhibitory effect of 13-cis and 13'-cis fucoxanthin on HL-60 cells and Caco-2 cells could possibly be due to their higher apoptosis-inducing activity. (C) 2008 Elsevier Ltd. All rights reserved.
• Eicosapentaenoic Acid Plays a Beneficial Role in Membrane Organization and Cell Division of a Cold-Adapted Bacterium, Shewanella livingstonensis Ac10

  Jun Kawamoto, Tatsuo Kurihara, Kentaro Yamamoto, Makiko Nagayasu, Yasushi Tani, Hisaaki Mihara, Masashi Hosokawa, Takeshi Baba, Satoshi B. Sato, Nobuyoshi Esaki

  JOURNAL OF BACTERIOLOGY 191 2 632 - 640 2009年01月 [査読有り][通常論文]
   

  Shewanella livingstonensis Ac10, a psychrotrophic gram-negative bacterium isolated from Antarctic seawater, produces eicosapentaenoic acid (EPA) as a component of phospholipids at low temperatures. EPA constitutes about 5% of the total fatty acids of cells grown at 4 degrees C. We found that five genes, termed orf2, orf5, orf6, orf7, and orf8, are specifically required for the synthesis of EPA by targeted disruption of the respective genes. The mutants lacking EPA showed significant growth retardation at 4 degrees C but not at 18 degrees C. Supplementation of a synthetic phosphatidylethanolamine that contained EPA at the sn-2 position complemented the growth defect. The EPA-less mutant became filamentous, and multiple nucleoids were observed in a single cell at 4 degrees C, indicating that the mutant has a defect in cell division. Electron microscopy of the cells by high-pressure freezing and freeze-substitution revealed abnormal intracellular membranes in the EPA-less mutant at 4 degrees C. We also found that the amounts of several membrane proteins were affected by the depletion of EPA. While polyunsaturated fatty acids are often considered to increase the fluidity of the hydrophobic membrane core, diffusion of a small hydrophobic molecule, pyrene, in the cell membranes and large unilamellar vesicles prepared from the lipid extracts was very similar between the EPA-less mutant and the parental strain. These results suggest that EPA in S. livingstonensis Ac10 is not required for bulk bilayer fluidity but plays a beneficial role in membrane organization and cell division at low temperatures, possibly through specific interaction between EPA and proteins involved in these cellular processes.
• Anti-obesity and anti-diabetic effects of fucoxanthin on diet-induced obesity conditions in a murine model

  Hayato Maeda, Masashi Hosokawa, Tokutake Sashima, Katsura Murakami-Funayama, Kazuo Miyashita

  Mol. Med. Reports 2 6 897 - 902 2009年 [査読有り][通常論文]
   

  Fucoxanthin, a characteristic carotenoid of brown algae, has been reported to exert an anti-diabetic effect in an obese murine model. Wakame (Undaria pinnatifida), an edible seaweed, is rich in fucoxanthin. This study examined the anti-obesity and anti-diabetic effects of fucoxanthin-rich wakame lipids (WLs) on high fat (HF) diet-induced obesity in mice. Mice were fed a high fat control (HF(C)) or normal fat control (NF(C)) diet for 10 weeks. The HF diet-fed group was administered a HF diet containing WLs for a further 5 weeks. Parameters related to diabetes and obesity conditions were evaluated and compared. The HF-WL diet, which was rich in fucoxanthin, significantly suppressed body weight and white adipose tissue (WAT) weight gain induced by the HF diet. Dietary administration of the HF diet resulted in hyperglycemia, hyperinsulinemia and hyperleptinemia in the mouse model. These perturbations were completely normalized in the HF-WL diet-fed group. Increased expression of monocyte chemoattractant protein-1 (MCP-1) mRNA expression was observed in HF(C) mice, but was normalized in the HF-WL groups. Moreover, the HF-WL diet promoted mRNA expression of beta 3-adrenergic receptor (Adrb3) in WAT and glucose transporter 4 (GLUT4) mRNA in skeletal muscle tissues. These results suggest that dietary WLs may ameliorate alterations in lipid metabolism and insulin resistance induced by a HF diet. There is therefore a biochemical and nutritional basis for the application of fucoxanthin-rich WLs as a functional food to prevent obesity and diabetes-related disorders.
• Application of Phospholipases for Highly Functional Phospholipid Preparation

  Masashi Hosokawa

  Biocatalysis and Agricultural Biotechnology 2009年
• Anti-Obesity Effect of Allene Carotenoids, Fucoxanthin and Neoxanthin from Seaweeds and Vegetables

  K. Miyashita, H. Maeda, T. Tsukui, T. Okada, M. Hosokawa

  II INTERNATIONAL SYMPOSIUM ON HUMAN HEALTH EFFECTS OF FRUITS AND VEGETABLES: FAVHEALTH 2007 841 167 - 171 2009年 [査読無し][通常論文]
   

  Obesity is one of the most prevalent nutritional disorders, and it results from an imbalance between energy intake and expenditure. We have found that carotenoids containing an allene bond, such as fucoxanthin and fucoxanthinol, showed anti-obesity effects with a new molecular mechanism. We showed significant reduction of WAT in wistar rats and obese KK-Ay mice by feeding both carotenoids. Clear signals of UCP1 protein and mRNA were detected by Western and Northern blot analyses in WAT in mice fed fucoxanthin, although there is little expression of UCP1 in WAT in mice fed the control diet. UCP1 expression in WAT by fucoxanthin intake leads to oxidation of fatty acids and heat production in WAT mitochondria. The substrate oxidation can directly reduce WAT in animals. We also found a relationship between carotenoid structure and anti-obesity properties, i.e., ability to suppress adipocyte differentiation. An examination of structure and function revealed that carotenoids containing an allene bond and an additional hydroxyl substituent on the side group show suppressive effects on adipocyte differentiation in 3T3-L1 cells. These findings show a great potential for application in the field of therapeutics for the development of novel anti-obesity compounds. Further, the suggestion that carotenoid health effects are likely linked to structural characteristics may help in the discovery of additional carotenoids that possess health-promoting properties.
• ANTI-OBESITY AND ANTI-DIABETIC EFFECT OF ALLENIC CAROTENOID

  Tomoko Okada, Hayato Maeda, Masashi Hosokawa, Kazuo Miyashita

  ANNALS OF NUTRITION AND METABOLISM 55 92 - 92 2009年 [査読有り][通常論文]
  
• Growth Inhibition and Induction of Apoptosis of Colon Cancer Cell Lines by Applying Marine Phospholipid

  Zakir Hossain, Masashi Hosokawa, Koretaro Takahashi

  NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL 61 1 123 - 130 2009年 [査読有り][通常論文]
   

  Polyunsaturated fatty acids (PUFAs) exhibit beneficial biological functions in carcinogenic processes. We examined the effects of PUFAs in the acid and phospholipid forms on three colon cancer cell lines (HT-29, Caco-2, and DLD-1). Docosahexaenoic acid (DHA) and eicosapentaenoic (EPA) in both acid and phospholipid forms showed growth inhibition effects on experimental colon cancer cell lines. But these PUFAs had the strongest growth-inhibitory effect on HT-29 than Caco-2 and DLD-1. Combined application of PUFAs and sodium butyrate (NaBt) increased the growth inhibition. Growth inhibition was apparently caused by increased lipid peroxidation. DHA or EPA in combination with NaBt significantly increased caspase-3 activity compared to control. DHA and DHA-rich phosphatidylcholine decreased Bcl-2 level in HT-29 and Caco-2 cells.
• New C-37 Skeletal Carotenoid from the Clam, Paphia amabillis

  Takashi Maoka, Naoshige Akimoto, Mi-Jin Yim, Masashi Hosokawa, Kazuo Miyashita

  JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 56 24 12069 - 12072 2008年12月 [査読有り][通常論文]
   

  Carotenoids in the muscle of Paphia amabillis (Veneridae) were investigated. Amarouciaxanthin 3-ester (11 a) was found to be a major carotenoid along with amarouciaxanthin A (1b), fucoxanthinol 3-ester (2), peridininol 3'-ester (3), and a new C-37 skeletal carotenoid, named hydratopyrrhoxanthinol Tester. This structure was determined to be 3'-acyloxy-3,5,6-trihydroxy-7',8'-didehydro-5,6-dihydro-12',13',20'-trinor-beta,beta-caroten-19,11-olide (4) by UV-vis, NMR, and FAB-MS spectral data. The absolute configuration of 4 was postulated to be (3S,5R,6R,3'R) on the bases of CD and ROESY data. The fatty acids esterified with hydratopyrrhoxanthinol were assigned as C22:6, C20:1, C20:4, C20:5, C18:0, C18:1, C17:0, C16:0, C16:1, and C14:0 on the basis of FAB-MS data.
• Cold adaptation of eicosapentaenoic acid-less mutant of Shewanella livingstonensis Ac10 involving uptake and remodeling of synthetic phospholipids containing various polyunsaturated fatty acids

  Sho Sato, Tatsuo Kurihara, Jun Kawamoto, Masashi Hosokawa, Satoshi B. Sato, Nobuyoshi Esaki

  EXTREMOPHILES 12 6 753 - 761 2008年11月 [査読有り][通常論文]
   

  An Antarctic psychrotrophic bacterium, Shewanella livingstonensis Ac10, produces cis-5,8,11,14,17-eicosapentaenoic acid (EPA), a long-chain polyunsaturated fatty acid (LPUFA), as a component of membrane phospholipids at low temperatures. The EPA-less mutant generated by disruption of the EPA synthesis gene becomes cold-sensitive. We studied whether the cold sensitivity could be suppressed by supplementation of various LPUFAs. The EPA-less mutant was cultured at 6 degrees C in the presence of synthetic phosphatidylethanolamines (PEs) that contained oleic acid at the sn-1 position and various C20 fatty acids with different numbers of double bonds from zero to five or cis-4,7,10,13,16,19-docosahexaenoic acid (DHA) at the sn-2 position. Mass spectrometric analyses revealed that all these fatty acids became components of various PE and phosphatidylglycerol species together with shorter partner fatty acids, indicating that large-scale remodeling followed the incorporation of synthetic PEs. As the number of double bonds in the sn-2 acyl chain decreased, the growth rate decreased and the cells became filamentous. The growth was restored to the wild-type level only when the medium was supplemented with phospholipids containing EPA or DHA. We found that about a half of DHA was converted into EPA. The results suggest that intact EPA is best required for cold adaptation of this bacterium.
• Effects of Trans and Conjugated LC N-3 Polyunsaturated Fatty Acids on Lipid Composition and Abdominal Fat Weight in Rats

  T. Okada, R. Noguchi, M. Hosokawa, K. Fukunaga, T. Nishiyama, N. Zaima, T. Hirata, K. Miyashita

  JOURNAL OF FOOD SCIENCE 73 8 H201 - H206 2008年10月 [査読有り][通常論文]
   

  Trans and conjugated fatty acids may exhibit either beneficial or detrimental bioactive effects depending on their metabolic properties. This study was conducted to elucidate if isomerization and conjugation of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) demonstrate more favorable bioactivity on lipid metabolism compared to unmodified EPA and DHA. The effects of dietary intake of trans and conjugated forms of EPA and DHA on lipid metabolism were evaluated in animal trials and compared to a control group fed soybean oil. None of the experimental diets showed significant differences from the control in terms of body weight; however, the white adipose tissue weight of rodents fed trans DHA, conjugated EPA (CEPA), and conjugated DHA (CDHA) was significantly lower than the control. Triacylglycerol levels in plasma were significantly decreased in groups fed trans DHA (17.2 mg/dL) and CDHA (31.9 mg/dL) relative to the control (51.3 mg/dL). The total cholesterol concentrations were significantly lower than the control (68.0 mg/dL) in all experimental groups (47.3 to 53.7 mg/dL) except CEPA (58.3 mg/dL). Fatty acid compositions of lipids extracted from rodent livers were influenced by the dietary fatty acid profiles, with all groups showing higher concentrations of stearic acid and lower levels of linoleic acid compared to the control. Rodents fed trans DHA did not have detectable levels of these fatty acid isomers in their livers, suggesting either quick metabolism or a difficulty with bio-absorption.
• Antiobesity effect of fucoxanthin from edible seaweeds and its multibiological functions

  Hayato Maeda, Masashi Hosokawa, Tokutake Sashima, Kazuo Miyashita

  ACS Symposium Series 993 376 - 388 2008年09月19日 [査読無し][通常論文]
   

  Fucoxanthin has a unique structure including an unusual allenic bond and 5,6-monoepoxide in its molecule. It induced a remarkable reduction in the growth of leukemia and prostate cancer cells. Furthermore, we have found that fucoxanthin showed anti-obesity effect with a new molecular mechanism. Uncoupling protein (UCP) is inner-membrane mitochondrial protein that has the ability to dissipate energy through uncoupling of oxidative phosphorylation which, instead of ATP, produces heat. A great deal of interest has focused on adaptive thermogenesis by UCP families (UCP1, 2 and 3) in several tissues and organs as a physiological defense against obesity, hyperlipidemia, and diabetes. In fact, UCP1 expression in brown adipose tissue (BAT) is known as a significant component of whole body energy expenditure, at least small rodents, and its dysfunction contributes to the development of obesity. However, adult humans have very little BAT, making it unlikely to be a major contributor to human weight regulation. In humans, most of fat is stored in white adipose tissue (WAT). Considered as breakthrough discoveries for an ideal therapy of obesity, regulation of UCP expression in white adipose tissue (WAT) by food constituent should be studied. Here, we show significant reduction of WAT in wistar rats and obese KK-Ay mice by feeding fucoxanthin (0.05 or 0.2 wt%/feed).Fucoxanthin, concentrated from edible seaweed, Undaria Pinnatifida (Japanese name is Wakame). The daily intake of fucoxanthin to KK-Ay mice also caused a significant reduction of body weight and a significant increase in BAT weight. Clear signals of UCP1 protein and mRNA were detected by Western and Northern blot analyses in WAT in mice fed fucoxanthin, although there is little expression of UCP1 in WAT in mice fed control diet. UCP1 expression in WAT by fucoxanthin intake leads to oxidation of fatty acids and heat production in WAT mitochondria. The substrate oxidation can directly reduce WAT in animals. © 2008 American Chemical Society.
• Synthesis of phosphatidylated-monoterpene alcohols catalyzed by phospholipase D and their antiproliferative effects on human cancer cells

  Yukihiro Yamamoto, Masashi Hosokawa, Hideyuki Kurihara, Takashi Maoka, Kazuo Miyashita

  BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 18 14 4044 - 4046 2008年07月 [査読有り][通常論文]
   

  In order to prepare functional phospholipids in the medical and pharmaceutical fields, perillyl alcohol, myrtenol, and nerol were transphosphatidylated via phospholipase D in an aqueous system. The yields of phosphatidyl-perillyl alcohol, -myrtenol, and -nerol were 79 mol %, 87 mol %, and 91 mol %, respectively. The synthetic phosphatidylated monoterpenes showed a markedly antiproliferative effect on human prostate PC-3 and human leukemia HL-60 cells at 100 mu M, while the free monoterpene alcohols had no effect at 400 mu M. (c) 2008 Elsevier Ltd. All rights reserved.
• Suppressive Effect of Neoxanthin on the Differentiation of 3T3-L1 Adipose Cells

  Tomoko Okada, Miho Nakai, Hayato Maeda, Masashi Hosokawa, Tokutake Sashima, Kazuo Miyashita

  JOURNAL OF OLEO SCIENCE 57 6 345 - 351 2008年06月 [査読有り][通常論文]
   

  The objective of this study was to assess the suppressive effects of 13 naturally occurring carotenoids on the adipocyte differentiation of 3T3-L1. The relationship between carotenoid structure and suppressive effects was also examined. Treatment with neoxanthin significantly reduced lipid accumulation, as well as glycerol-3-phosphate dehydrogenase activity. This suppressive effect on adipose cell differentiation was not observed in the other 12 carotenoids used in this study. Neoxanthin treatment also decreased expression of CCAAT/enhancer binding protein alpha (C/EBP alpha) and peroxisome proliferator-activated receptor gamma (PPAR gamma) mRNAs. An examination of structure and function suggested that carotenoids containing an allene bond and an additional hydroxyl substituent on the side group may show suppressive effects on adipocyte differentiation in 3T3-L1 cells.
• Preparation of phosphatidylated terpenes via phospholipase D-mediated transphosphatidylation

  Yukihiro Yamamoto, Masashi Hosokawa, Hideyuki Kurihara, Kazuo Miyashita

  JOURNAL OF THE AMERICAN OIL CHEMISTS SOCIETY 85 4 313 - 320 2008年04月 [査読有り][通常論文]
   

  Terpenes such as geraniol, geranylgeraniol, farnesol, and phytol are known as functional compounds which exhibit anticancer effects and activate nuclear receptors. For the application of functional terpenes in various fields, including the cosmetic and food industries, we attempted to synthesize phosphatidylated terpenes (terpene-PLs) by using phospholipase D (PLD). Transphosphatidylation of phosphatidylcholine with terpenes was carried out using PLD in a biphasic system containing ethyl acetate/water or in an aqueous system without organic solvent. The yield of terpene-PL increased with the reaction time and the amount of PLD in both the biphasic and aqueous systems. Further, the yield of terpene-PL in the aqueous system was higher than that in the biphasic system. In addition, among four PLDs from Streptomyces sp., Streptomyces chromofuscus, cabbage, and peanut, only the PLD from Streptomyces sp. could synthesize terpene-PL. The reaction yield, based on substrate phospholipid, of phosphatidylgeraniol reached 90 mol% under the following optimal reaction conditions: 50 mu mol soyPC; 2,000 mu mol geraniol; 1.6 U PLD; 0.8 ml of 0.2 M sodium acetate buffer (pH 5.6); temperature, 37 degrees C ; and reaction time, 24 h. The reaction yields of phosphatidylfarnesol, phosphatidylgeranylgeraniol, and phosphatidylphytol were 73, 54, and 17 mol%, respectively.
• Multi-functional carotenoid in seaweeds: fucoxanthin

  Kazuo Miyashita, Masashi Hosokawa

  NIPPON SUISAN GAKKAISHI 74 2 261 - 262 2008年03月 [査読有り][通常論文]
  
• Suppressive Effects of Alloxanthin and Diatoxanthin from Halocynthia roretzi on LPS-induced Expression of Pro-inflammatory Genes in RAW264.7 Cells

  Izumi Konishi, Masashi Hosokawa, Tokutake Sashima, Takashi Maoka, Kazuo Miyashita

  JOURNAL OF OLEO SCIENCE 57 3 181 - 189 2008年03月 [査読有り][通常論文]
   

  To investigate anti-inflammatory effects of carotenoids from Halocynthia roretzi, gene expression levels were measured for pro-inflammatory cytokines and enzymes in the murine macrophage-like cell line, RAW264.7, stimulated with lipopolysaccharide (LPS). All-trans alloxanthin, all-trans diatoxanthin, and their 9-cis isomers isolated from H. roretzi significantly suppressed expression of IL-1 beta and IL-6 mRNA in cells induced by LIPS without cytotoxicity. The expression level of IL-1 beta mRNA in cells treated with 25 mu M all-trans alloxanthin for 24 h, followed by stimulation with 0.1 mu g/mL LPS for 24 h in the presence of carotenoid decreased to 33.7 +/- 3.0% from that of control cells stimulated with LPS alone. All-trans diatoxanthin, 9-cis alloxanthin and 9-cis diatoxanthin also decreased expression of IL-1 beta mRNA to 25.1 +/- 2.1, 28.2 +/- 0.9 and 32.9 +/- 3.3%, respectively, from that of control cells stimulated with LPS. IL-1 beta production in culture medium was also suppressed by all-trans alloxanthin and all-trans diatoxanthin. Furthermore, all-trans alloxanthin, all-trans diatoxanthin and their 9-cis isomers suppressed the overexpression of cyclooxygenase-2 and nitric oxide synthase mRNA in RAW264.7 cells induced by LPS. The suppressive effects of these carotenoids were remarkable compared to those of beta-carotene and zeaxanthin.
• Enzymatic Production of Marine-Derived Protein Hydrolysates and Their Bioactive Peptides for Use in Foods and Nutraceuticals

  Tomoko Okada, Masashi Hosokawa, Seigo Ono, Kazuo Miyashita

  Biocatalysis and Bioenergy 491 - 519 2008年02月25日 [査読有り][通常論文]
  
• Composition, Functionality and Potential Applications of Seaweed Lipids

  Bhaskar Narayan, Chandini S. Kumar, Tokutake Sashima, Hayato Maeda, Masashi Hosokawa, Kazuo Miyashita

  Biocatalysis and Bioenergy 463 - 490 2008年02月25日 [査読有り][通常論文]
  
• Seaweed carotenoid, fucoxanthin, as a multi-functional nutrient

  Hayato Maeda, Takayuki Tsukui, Tokutake Sashima, Masashi Hosokawa, Kazuo Miyashita

  ASIA PACIFIC JOURNAL OF CLINICAL NUTRITION 17 196 - 199 2008年 [査読有り][通常論文]
   

  Fucoxanthin has a unique structure including an unusual allenic bond and 5, 6-monoepoxide in its molecule. We found that abdominal white adipose tissue (WAT) weights of rats and mice fed fucoxanthin were significantly lower than those fed a control diet. The daily intake of fucoxanthin in mice also caused a significant reductions of body weight. Clear signals of uncoupling protein 1 (UCP1) and its mRNA were detected by Western and Northern blot analyses in abdominal WAT in mice fed fucoxanthin, although there is little expression of UCP1 in WAT in mice fed a control diet. UCP1 expression in WAT by fucoxanthin intake leads to oxidation of fatty acids and heat production in WAT mitochondria. Substrate oxidation can directly reduce WAT in animals. Fucoxanthin intake also significantly reduced blood glucose and plasma insulin. Furthermore, feeding fucoxanthin significantly increased the level of hepatic docosahexaenoic acid (DHA), a most important n-3 functional polyunsaturated fatty acid in biological systems. These multi-functionalities of fucoxanthin indicate that it is an important bioactive carotenoid that is should be beneficial for the prevention of the metabolic syndrome.
• Radical scavenging and singlet oxygen quenching activity of marine carotenoid fucoxanthin and its metabolites

  Nakkarike M. Sachindra, Emiko Sato, Hayato Maeda, Masashi Hosokawa, Yoshimi Niwano, Masahiro Kohno, Kazuo Miyashita

  JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 55 21 8516 - 8522 2007年10月 [査読有り][通常論文]
   

  Antioxidant activity of carotenoids is suggested to be one of the factors; for their disease preventing effects. Marine carotenoids fucoxanthin and its two metabolites, fucoxanthinol and halocynthiaxanthin, have been shown to exhibit several biological effects. The antioxidant activities of these three carotenoids were assessed in vitro with respect to radical scavenging and singlet oxygen quenching abilities. The 1,1 -diphenyl-2-picrylhydrazyl radical scavenging activity of fucoxanthin and fucoxanthinol was higher than that of halocynthiaxanthin, with the effective concentration for 50% scavenging (EC50) being 164.60, 153.78, and 826.39 mu M, respectively. 2,2'-Azinobis-3-ethylbenzo thizol ine-6-su I phonate radical scavenging activity of fucoxanthinol (EC50, 2.49 mu M) was stronger than that of fucoxanthin (EC50, 8.94 mu M). Hydroxyl radical scavenging activity as measured by the chemiluminescence technique showed that the scavenging activity of fucoxanthin was 7.9 times higher than that by fucoxanthinol, 16.3 times higher than that by halocynthiaxanthin, and 13.5 times higher than that by (x-tocopherol. A similar trend was observed when the hydroxyl radical scavenging was assessed by the electron spin resonance (ESR) technique. ESR analysis of the Superoxide radical scavenging activity also showed the superiority of fucoxanthin over the other two carotenoids tested. Singlet oxygen quenching ability of the three carotenoids was lower than that of beta-carotene, with quenching rate constants (k(Q), x 10(10) M-1 s(-1)) being 1.19, 1.81, 0.80, and 12.78 for fucoxanthin, fucoxanthinol, halocynthiaxanthin, and beta-carotene, respectively. The higher radical scavenging activity of fucoxanthin and fucoxanthinol compared with halocynthiaxanthin is assumed to be due to presence of the allenic bond.
• Dietary combination of fucoxanthin and fish oil attenuates the weight gain of white adipose tissue and decreases blood glucose in obese/diabetic KK-A(y) mice

  Hayato Maeda, Masashi Hosokawa, Tokutake Sashima, Kazuo Miyashita

  JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 55 19 7701 - 7706 2007年09月 [査読有り][通常論文]
   

  Fucoxanthin is a marine carotenoid found in edible brown seaweeds. We previously reported that dietary fucoxanthin attenuates the weight gain of white adipose tissue (WAT) of diabetic/obese KK-A(y) mice. In this study, to evaluate the antiobesity and antidiabetic effects of fucoxanthin and fish oil, we investigated the effect on the WAT weight, blood glucose, and insulin levels of KK-Ay mice. Furthermore, the expression level of uncoupling protein 1 (UCP1) and adipokine mRNA in WAT were measured. After 4 weeks of feeding, 0.2% fucoxanthin in the diet markedly attenuated the gain of WAT weight in KK-Ay mice with increasing UCP1 expression compared with the control mice. The WAT weight of the mice fed 0.1% fucoxanthin and 6.9% fish oil was also significantly lower than that of the mice fed fucoxanthin alone. In addition, 0.2% fucoxanthin markedly decreased the blood glucose and plasma insulin concentrations in KK-Ay mice. The mice fed with the combination diet of 0.1% fucoxanthin and fish oil also showed improvements similar to that of 0.2% fucoxanthin. Leptin and tumor necrosis factor (TNF alpha) mRNA expression in WAT were significantly down-regulated by 0.2% fucoxanthin. These results suggest that dietary fucoxanthin decreases the blood glucose and plasma insulin concentration of KK-Ay along with down-regulating TNFa mRNA. In addition, the combination of fucoxanthin and fish oil is more effective for attenuating the weight gain of WAT than feeding with fucoxanthin alone.
• Occurrence of conjugated cyclopropanoid acid in purified fish oil

  Naoto Horii, Shingo Arato, Bhaskar Narayan, Masashi Hosokawa, Tokutake Sashima, Kazuo Miyashita

  JOURNAL OF THE AMERICAN OIL CHEMISTS SOCIETY 84 8 749 - 754 2007年08月 [査読有り][通常論文]
   

  The presence of conjugated trienoic acids were found in the purified fish oil from the Japanese sardine by an analysis of high performance liquid chromatography equipped with a photodiode-array detector. Gas chromatography-mass spectrometry indicated that main conjugated trienoic acids were those of 16:3, 20:5, and 22:6. Conjugated trienoic acid of 16:3 was identified as a cyclopropanoid acid with conjugated triene by NMR analysis. All conjugated trienoic acids were formed by heat treatment during the deodorization of fish oil, but not found after de-gumming, alkaline refining, and bleaching. Conjugated trienoic acids of 16:3, 20:5, and 22:6 originated from 16:4n-1, 20:5n-3 (EPA), and 22:6n-3 (DHA) in the fish oil during the heat treatment for deodorization.
• Oxidative stability of salmon and herring roe lipids and their dietary effect on plasma cholesterol levels of rats

  Hiromi Moriya, Takashi Kuniminato, Masahi Hosokawa, Kenji Fukunaga, Toshimasa Nishiyama, Kazuo Miyashita

  FISHERIES SCIENCE 73 3 668 - 674 2007年06月 [査読有り][通常論文]
   

  The oxidative stability of lipids from salmon roe and herring roe was compared with those of commercial fish oils originated from sardine and tuna. Both fish roe lipids contained high amounts of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Total EPA and DHA was more than 35% of total fatty acids in both roe lipids. On the basis of oxygen consumption, fish roe lipids showed the higher oxidative stability than both fish oils. This tendency in oxidative stabilities was also confirmed by the determination of propanal formation during oxidation. Analyses of lipid compositions suggested that the higher oxidative stabilities of fish roe lipids would be mainly due to the presence of phospholipids in them. Dietary effects of salmon and herring roe lipids were also determined. Little increase in total cholesterol level was observed in plasma lipids in rats fed salmon and herring roe lipids, although cholesterol content in fish roe lipids were 6.3% and 9.7% of total lipids for salmon roe and herring roe.
• Combination effect of herring roe lipids and proteins on plasma lipids and abdominal fat weight of mouse

  H. Moriya, M. Hosokawa, K. Miyashita

  JOURNAL OF FOOD SCIENCE 72 5 C231 - C234 2007年06月 [査読有り][通常論文]
   

  Dietary effects of herring roe lipids (HR-L) and proteins (HR-P) on plasma lipids and abdominal fat pad weight were determined. The main lipid class of HR-L was phospholipids (74%) and the main fatty acids were palmitic acid (16:0, 25.8%), DHA (22:6n-3, 21.6%), EPA (20:5n-3, 14.4%), and oleic acid (18:1n-9, 13.2%). A little increase in total cholesterol level was observed in plasma lipids of mouse fed with HR-L, although HR-L contained 9% cholesterol. This would be due to the lowering effect of EPA and DHA contained in HR-L on plasma cholesterol. Replacement of a part of dietary protein (5%) to HR-P reduced abdominal fat pad weight, but not significantly. On the other hand, combination of HR-P and HR-L significantly reduced the fat pad weight of the mouse as compared with the control. A sigificant effect of HR-P + HR-L was also observed in the reducing plasma lipid levels.
• Fucoxanthin and fucoxanthinol enhance the amount of docosahexaenoic acid in the liver of KKAy obese/diabetic mice

  Takayuki Tsukui, Kensuke Konno, Masashi Hosokawa, Hayato Maeda, Tokutake Sashima, Kazuo Miyashita

  JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 55 13 5025 - 5029 2007年06月 [査読有り][通常論文]
   

  This study examined the effect of dietary fucoxanthin or fucoxanthinol on the amount of docosahexaenoic acid (DHA) in the liver of KKAy mice, a model for obese/type II diabetes. In the first experiment, mice were fed diets containing crude fucoxanthin or glyceroglycolipid for 4 weeks. Results showed a significant increase in the level of DHA in mice fed 0.53% crude fucoxanthin, from 2.3% in control mice to 5.1% of fatty acid composition of total liver lipids. On the other hand, in mice fed crude glyceroglycolipid, the level of DHA as a proportion of total liver fatty acids remained unchanged. To clarify the enhancement of hepatic DHA, in the second experiment, KKAy mice were fed a diet containing purified fucoxanthin or its deacetylated derivative, fucoxanthinol. Results from a quantitative analysis using an internal standard showed that in mice fed 0.2% fucoxanthin, the amount of hepatic DHA was 2-fold higher than in control mice, whereas DHA levels in the small intestine remained unchanged. Furthermore, 0.2% fucoxanthinol led to 1.8- and 1.2-fold increases in the amount of hepatic DHA and arachidonic acid compared to control mice, respectively. These results indicate for the first time that dietary fucoxanthin and fucoxanthinol enhance the amount of DHA in the liver of KKAy mice.
• Therapy of myeloma in vivo using marine phospholipid in combination with agaricus blazei murill as immune respond activator.

  Murakawa Kentaro, Fukunaga Kenji, Tanouchi Masatoshi, Hosokawa Masashi, Hossain Zakir, Takahashi Koretaro

  J. Oleo Sci. 56 4 179 - 188 Japan oil chemists' society 2007年 [査読有り][通常論文]
   

  Mushroom (Agaricus blazei Murill) extract has been reported to possess antitumor effects through immune activation. Here, we investigated the beneficial effects of combining A. blazei extract with marine phospholipids in comparison to A. blazei extract alone on myeloma sp2 tumor suppression when orally administrated. The experimental groups designed for sp2 tumor bearing BALB/c nu/nu mice were drinks of: (1)control; (2)1.0 mg/mL squid phospholipid liposome alone; (3)0.5 mg/mL A. blazei Murill water extract alone; (4)1.0 mg/mL squid phospholipid liposome with 0.5 mg/mL A. blazei Murill water extract in the form of those simple mixture; and (5)1.0 mg/mL squid phospholipid liposome with 0.5 mg/mL A. blazei Murill water extract partially encapsulated. Orally administrated volumes amounted to approximately 5 mL per day per mouse for all groups. A. blazei Murill water extract alone and squid phospholipid alone served groups show moderate tumor suppression with total administrations of approximately 105 mg/mouse for squid phospholipid through out the experimental term. When both A. blazei Murill water extract and squid phospholipid were administrated simultaneously in a simple mixture form, promotional effect on cancer tumor suppression was observed. And when A. blazei Murill water extract was partially encapsulated in the squid phospholipid liposomes with total administrations being 105 mg/mouse for squid phospholipid, effect on cancer tumor suppression was more pronounced. Though there was no statistically significant difference in tumor sizes between the simple mixture form administrated group i.e. group (4) and the partially encapsulated form administrated group i.e. group (5), the tumor vanished mouse was seen in the partially encapsulated form administrated group. Thus it was concluded that combinational administration of the A. blazei Murill water extract and the marine phospholipid may be useful in myeloma sp2 therapy.
• Unsaturated phosphatidylethanolamine as effective synergist in combination with alpha-tocopherol.

  TAKENAKA Atsushi, HOSOKAWA Masashi, MIYASHITA Kazuo

  J. Oleo Sci. 56 10 511 - 516 Japan Oil Chemists' Society 2007年 [査読有り][通常論文]
   

  The effects of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) on the oxidation of bonito oil triacylglycerol (TAG) were examined under the absence or presence of α-tocopherol. Synthesized PC or PE having saturated and unsaturated fatty acids in known position were used in this study. Unsaturated PC and PE promoted TAG oxidation under the absence of α-tocopherol. On the contrary, unsaturated PE showed synergistic antioxidant effect with α-tocopherol, while PC had little effect. The strongest synergistic effect was found by 1-palmitoyl (16:0, PA)-2-docosahexaenoyl (22:6n-3)-PE, followed by 1-PA-2-arachidonyl (20:4n-6)-PE, 1,2-dioleoyl (18:1n-9)-PE, and 1-PA-2-linoleoyl (18:2n-6)-PE, respectively.
  
• Effect of medium-chain triacylglycerols on anti-obesity effect of fucoxanthin.

  MAEDA Hayato, HOSOKAWA Masashi, SASHIMA Tokutake, FUNAYAMA Katsura, MIYASHITA Kazuo

  J. Oleo. Sci. 56 12 615 - 621 12 2007年 [査読有り][通常論文]
   

  Dietary effects of medium-chain triacylglycerols (MCT) and fucoxanthin (Fc) on abdominal fat weight were determined using KK-Ay obese mouse. Experimental diet contained MCT(0.9%), Fc (0.1%), or MCT (0.9%) +Fc (0.1%). The abdominal fat weight of mice fed with Fc was significantly lower than that of mice fed with MCT. Uncoupling protein 1 (UCP1), a key molecule for metabolic thermogenesis, was clearly expressed in the white adipose tissue (WAT) of mice fed Fc, but little expression in that of the mice fed MCT. The anti-obesity effect of Fc was increased by mixing Fc with MCT. This increase would be due to the increase in the absorption rate of Fc by MCT.
  
• Occurrence of conjugated linolenic acids in purified soybean oil

  Tomohisa Kinami, Naoto Horii, Bhaskar Narayan, Shingo Arato, Masashi Hosokawa, Kazuo Miyashita, Hironori Negishi, Junichi Ikuina, Ryuji Noda, Seiichi Shirasawa

  JOURNAL OF THE AMERICAN OIL CHEMISTS SOCIETY 84 1 23 - 29 2007年01月 [査読有り][通常論文]
   

  A high-performance liquid chromatographic (HPLC) method is described for the determination of conjugated linoleic acids (CLA) and conjugated linolenic acids (CLN). Methyl esters prepared from purified lipid fractions of soybean oil were analyzed using an HPLC system equipped with photodiode-array detector to detect peaks having maximum absorption around 233 and 275 nm. These peaks were concentrated by AgNO3-silicic acid column chromatography and reversed-phase HPLC. The structural analysis, of dimethyloxazoline (DMOX) derivatized methyl esters, using gas chromatography-mass spectrometry (GC-MS) showed the occurrence of 9,11- and 10,12-CLA and 8,10,13-, 8,10,12-, and 9,11,13-CLN. The comparison of these conjugated fatty acids with authentic isomers by HPLC revealed the presence of isomeric mixtures of CLA [cis (c),trans(t) or t,c and t,t] and CLN (c,t,t or t,t,c and t,t,t). Traces of 9,11- and 10,12-CLA (c,t or t,c) were found in crude oil. CLN isomers (8,10,12-18:3 and 9,11,13-18:3) were found to be forming during the bleaching phase of soybean oil processing. 8,10,13-CLN and 9,11- and 10,12-CLA (t,t) were only found in soybean oil after the deodorization step. CLN contents in commercial soybean oil varied from 387 to 1,316 mg/kg oil. A decreased level of bleaching earth and temperature resulted in a reduced CLN content. It is possible that CLN would be derived from the linoleate hydroperoxides formed during the processing and storage of soybean oil.
• Unsaturated phosphatidylethanolamine as effective synergist in combination with alpha-tocopherol.

  Takenaka A, Hosokawa M, Miyashita K

  Journal of oleo science 56 10 511 - 516 10 2007年 [査読有り][通常論文]
   

  The effects of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) on the oxidation of bonito oil triacylglycerol (TAG) were examined under the absence or presence of α-tocopherol. Synthesized PC or PE having saturated and unsaturated fatty acids in known position were used in this study. Unsaturated PC and PE promoted TAG oxidation under the absence of α-tocopherol. On the contrary, unsaturated PE showed synergistic antioxidant effect with α-tocopherol, while PC had little effect. The strongest synergistic effect was found by 1-palmitoyl (16:0, PA)-2-docosahexaenoyl (22:6n-3)-PE, followed by 1-PA-2-arachidonyl (20:4n-6)-PE, 1,2-dioleoyl (18:1n-9)-PE, and 1-PA-2-linoleoyl (18:2n-6)-PE, respectively.
  
• 9trans,11trans conjugated linoleic acid inhibits the development of azoxymethane-induced colonic aberrant crypt foci in rats

  Yumiko Yasui, Rikako Suzuki, Hiroyuki Kohno, Shingo Miyamoto, Fumiaki Beppu, Masashi Hosokawa, Kazuo Miyashita, Takuji Tanaka

  NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL 59 1 82 - 91 2007年 [査読有り][通常論文]
   

  We investigated the effects of 9trans,11trans (9t,11t)-conjugated linoleic acid (CLA) isomer on azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) in rats. Male F344 rats were given 2 weekly subcutaneous injections of AOM (20 mg/kg bw) to induce colonic ACF. They also were fed a diet containing either 0.01%, 0.1%, or 1% 9t,11t-CLA for 4 wk starting 1 wk before the first dosing of AOM. The group that received a diet supplemented with 90 11t-CLA had a significantly lower number of ACF/colon in comparison to the AOM alone group in a dose-dependent manner up to 0.1%. Furthermore, treatment with 9t, 11t-CLA induced apoptosis and suppressed cell proliferation activity in the non-lesional crypts. The downregulation of cyclooxygenase-2 and cyclin D1 and the activation of peroxisome proliferators activated receptor gamma were observed in the colonic mucosa of rats fed a diet supplemented with 9t, 11t-CLA. Our findings thus provide some novel insight into the chemopreventive effect of 9t,11t-CLA against preinitiation as well as postinitiation stages of colorectal carcinogenesis.
• Potent inhibitory effect of trans9, trans 11 isomer of conjugated linoleic acid on the growth of human colon cancer cells

  Fumiaki Beppu, Masashi Hosokawa, Leo Tanaka, Hiroyuki Kohno, Takuji Tanaka, Kazuo Miyashita

  JOURNAL OF NUTRITIONAL BIOCHEMISTRY 17 12 830 - 836 2006年12月 [査読有り][通常論文]
   

  This study compared the growth inhibitory effects of pure conjugated linoleic acid (CLA) isomers [cis(c)9,c11-CLA, c9,trans(t)11-CLA, t9,t11-CLA, and t10,c12-CLA] on human colon cancer cell lines (Caco-2, HT-29 and DLD-1). When Caco-2 cells were incubated up to 72 h with 200 mu M, each isomer, even in the presence of 10% fetal bovine serum (FBS), cell proliferation was inhibited by all CLA isomers in a time-dependent manner. The strongest inhibitory effect was shown by t9,t11-CLA, followed by t10,c12-CLA, c9,c11-CLA and c9,t11-CLA, respectively. The strongest effect of t9,t11-CLA was also observed in other colon cancer cell lines (HT-29 and DLD-1). The order of the inhibitory effect of CLA isomer was confirmed in the presence of 1% FBS. CLA isomers supplemented in the culture medium were readily incorporated into the cellular lipids of Caco-2 and changed their fatty acid composition. The CLA contents in cellular lipids were 26.2 +/- 2.7% for t9,t11-CLA, 35.9 +/- 0.3% for c9,t11-CLA and 46.3 +/- 0.8% for t10,c12-CLA, respectively. DNA fragmentation was clearly recognized in Caco-2 cells treated with t9,t11-CLA. This apoptotic effect of t9,t11-CLA was dose- and time-dependent. DNA fragmentation was also induced by 9c,11t-CLA and t10,c12-CLA. However, fragmentation levels with both isomers were much lower than that with t9,t11-CLA. t9t11-CLA treatment of Caco-2 cells decreased Bcl-2 levels in association with apoptosis, whereas Bax levels remained unchanged. These results suggest that decreased expression of Bcl-2 by t9t11-CLA might increase the sensitivity of cells to lipid peroxidation and to programmed cell death, apoptosis. (c) 2006 Elsevier Inc. All rights reserved.
• Catalpa seed oil rich in 9t,11t,13c-conjugated linolenic acid suppresses the development of colonic aberrant crypt foci induced by azoxymethane in rats

  Rikako Suzuki, Yumiko Yasui, Hiroyuki Kohno, Shingo Miyamoto, Masashi Hosokawa, Kazuo Miyashita, Takuji Tanaka

  ONCOLOGY REPORTS 16 5 989 - 996 2006年11月 [査読有り][通常論文]
   

  Catalpa (Catalpa ovata) seed oil (CPO) is a unique oil that contains a high amount of 9trans,11trans,13cis-conjugated linolenic acid. In the present study, we investigated whether dietary administration with CPO affects the development of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) in male F344 rats to elucidate its possible cancer chemopreventive efficiency. Also, the effect of CPO on the fatty acid composition of liver tissue and colonic mucosa, the serum levels of total cholesterol and triglyceride, and the mRNA expression of cyclooxygenase (COX)-2 in the colonic mucosa were measured. In addition, the cell proliferation activity and apoptotic index in the colonic mucosa were estimated immunohistochemically. Animals were given two weekly subcutaneous injections of AOM (20 mg/kg body weight). They also received the experimental diet containing 0.01 %, 0.1 % or 1 % CPO for 4 weeks, starting one week before the first dosing of AOM. AOM exposure produced a substantial number of ACF (99 28) at the end of the study (week 4). Dietary administration of CPO reduced the number of ACF (AOM + 0.01 % CPO, 32 +/- 11, P < 0.001; AOM + 0.1 % CPO, 35 +/- 18, P < 0.001; AOM + 1% CPO, 18 10, P < 0.001). 9t,11t-conjugated linoleic acid was detected in the liver tissue and colonic mucosa of rats fed the CPO-containing diet. Additionally, dietary administration with CPO decreased the serum triglyceride level and the expression of COX-2 mRNA in the colonic mucosa. The indices of cell proliferation and apoptosis in the colonic mucosa of rats treated with AOM and 1% CPO have significant differences when compared with the AOM alone group. These findings suggest the possible chemopreventive activity of CPO in the early phase of colon carcinogenesis.
• Production of phosphatidylcholine containing conjugated linoleic acid mediated by phospholipase A(2)

  Yukihiro Yamamoto, Masashi Hosokawa, Kazuo Miyashita

  JOURNAL OF MOLECULAR CATALYSIS B-ENZYMATIC 41 3-4 92 - 96 2006年08月 [査読有り][通常論文]
   

  Esterification of lysophosphatidylcholine (LPC) with conjugated linoleic acid (CLA) was carried out using porcine pancreatic phospholipase A(2) (PLA(2)). PLA(2) only slightly synthesized phosphatidylcholine containing CLA (CLA-PC) at 2.6% by the addition of water. Addition of formamide in place of water markedly increased the yield of CLA-PC. In addition, synthesis of CLA-PC by PLA(2) was affected by the amount of substrate CLA and PLA(2) in the reaction system. Under optimal reaction conditions using 11 mg LPC, 18 mg CLA, 550 mg glycerol, 50 mu L formamide, 3.3 x 10(4) U PLA(2), and 0.3 mu mol CaCl2 at 37 degrees C for 6 h, the reaction yield of CLA-PC reached 65 mol%. Furthermore, addition of protein such as albumin and casein suppressed the decrease of CLA-PC yield after 6 h. PLA(2) exhibited the highest activity for the 10t,12c-CLA isomer among four CLA isomers (9c,11t-CLA,9c,11c-CLA,9t,11t-CLA and 10t,12c-CLA), whereas that for 9c,11c-CLA was the lowest. These results showed that the present esterification system for LPC and CLA by PLA(2) is effective for producing CLA-PC. (c) 2006 Elsevier B.V. All rights reserved.
• Production of docosahexaenoic acid bounded phospholipids via phospholipase A(2) mediated bioconversion

  Shinichi Awano, Koji Miyamoto, Masashi Hosokawa, Mitsumasa Mankura, Koretaro Takahashi

  FISHERIES SCIENCE 72 4 909 - 911 2006年08月 [査読有り][通常論文]
  
• Fucoxanthin and its metabolite, fucoxanthinol, suppress adipocyte differentiation in 3T3-L1 cells

  Hayato Maeda, Masashi Hosokawa, Tokutake Sashima, Nobuyuki Takahashi, Teruo Kawada, Kazuo Miyashita

  INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 18 1 147 - 152 2006年07月 [査読有り][通常論文]
   

  Fucoxanthin is a major carotenoid found in edible seaweed such as Undaria pinnatifida and Hijikia fusiformis. We investigated the suppressive effects of fucoxanthin and its metabolite, fucoxanthinol, on the differentiation of 3T3-L1 preadipocytes to adipocytes. Fucoxanthin inhibited intercellular lipid accumulation during adipocyte differentiation of 3T3-L1 cells. Furthermore, fucoxanthin was converted to fucoxanthinol in 3T3-L1 cells. Fucoxanthinol also exhibited suppressive effects on lipid accumulation and decreased glycerol-3-phosphate dehydrogenase activity, an indicator of adipocyte differentiation. The suppressive effect of fucoxanthinol was stronger than that of fucoxanthin. In addition, in 3T3-L1 cells treated with fucoxanthin and fucoxanthinol, peroxisome proliferator-activated receptor gamma (PPAR gamma), which regulates adipogenic gene expression, was down-regulated in a dose-dependent manner. These results suggest that fucoxanthin and fucoxanthinol inhibit the adipocyte differentiation of 3T3-L1 cells through down-regulation of PPAR gamma. Fucoxanthinol had stronger suppressive effects than fucoxanthin on adipocyte differentiation in 3T3-L1 cells.
• Growth inhibition and apoptosis induction by all-trans-conjugated linolenic acids on human colon cancer cells

  Yumiko Yasui, Masashi Hosokawa, Hiroyuki Kohno, Takuji Tanaka, Kazuo Miyashita

  ANTICANCER RESEARCH 26 3A 1855 - 1860 2006年05月 [査読有り][通常論文]
   

  Conjugated linolenic acids (CLN) are geometric and positional isomers of linolenic acid. Growth inhibition and apoptosis induction by a-eleostearic acid (c.9,t11,t13-CLN), P-eleostearic acid (t9, t11, t13-CLN), a-calendic acid (t8.t10, c12-CLN) and P-calendic acid (t8, t10, t12-CLN) were compared. beta-Eleostearic acid and P-calendic acid, which have all-transconjugated double bonds, exerted stronger growth inhibition and more DNA fragmentation, an indicator of apoptosis induction, in the human colon cancer cells Caco-2 than a-eleostearic acid and a-calendic acid with the cis configuration. Down-regulation of bcl-2 and up-regulation of bax mRNA by beta-eleostearic acid were also greater than by a-eleostearic acid. Interestingly, the cytotoxic effects of beta-eleostearic acid and beta-calendic acid. were not counteracted completely by a-tocopherol. whereas the cytotoxic effects of a-eleostearic and a-calendic acids were lost in the presence of a-tocopherol. These results suggest that P-eleostearic and beta-calendic acids have signaling pathways different from those of a-eleostearic and a-calendic acids and exhibit high potency for reducing the cell viability of Caco-2.
• Growth inhibition and apoptosis induction by all-trans-conjugated linolenic acids on human colon cancer cells

  Yumiko Yasui, Masashi Hosokawa, Hiroyuki Kohno, Takuji Tanaka, Kazuo Miyashita

  Anticancer Research 26 3 A 1855 - 1860 2006年05月 [査読有り][通常論文]
   

  Conjugated linolenic acids (CLN) are geometric and positional isomers of linolenic acid. Growth inhibition and apoptosis induction by α-eleostearic acid (c9,t11,t13-CLN), β-eleostearic acid (t9,t11,t13-CLN), α-calendic acid (t8,t10,c12-CLN) and β-calendic acid (t8,t10,t12-CLN) were compared, β-Eleostearic acid and β-calendic acid, which have all-trans-conjugated double bonds, exerted stronger growth inhibition and more DNA fragmentation, an indicator of apoptosis induction, in the human colon cancer cells Caco-2 than α-eleostearic acid and α-calendic acid with the cis configuration. Down-regulation of bcl-2 and up-regulation of bax mRNA by β-eleostearic acid were also greater than by α-eleostearic acid. Interestingly, the cytotoxic effects of β-eleostearic acid and β-calendic acid were not counteracted completely by α-tocopherol, whereas the cytotoxic effects of α-eleostearic and α-calendic acids were lost in the presence of α-tocopherol. These results suggest that β-eleostearic and β-calendic acids have signaling pathways different from those of α-eleostearic and α-calendic acids and exhibit high potency for reducing the cell viability of Caco-2.
• Inhibition properties of dipeptides from salmon muscle hydrolysate on angiotensin I-converting enzyme

  S Ono, M Hosokawa, K Miyashita, K Takahashi

  INTERNATIONAL JOURNAL OF FOOD SCIENCE AND TECHNOLOGY 41 4 383 - 386 2006年04月 [査読有り][通常論文]
   

  We isolated Phe-Leu as an angiotensin I-converting enzyme (ACE) inhibitor from hydrolysate of chum salmon muscle. The IC50 value of this peptide was 13.6 mu M, and it showed non-competitive inhibition. The reverse sequence dipeptide Leu-Phe also showed ACE inhibitory activity. However, Leu-Phe is much less inhibitory than Phe-Leu with an IC50 value of 383.2 mu M. In addition, the inhibition mode was competitive. To investigate the relationship between dipeptide sequence and ACE inhibition properties, we further measured ACE inhibitory activity and inhibition mechanism using six Trp-containing dipeptides, which had been identified from the same salmon muscle hydrolysate as ACE inhibitory peptides in a previous study. Peptides with Trp as the C-terminal residue, Ala-Trp, Val-Trp, Met-Trp, Ile-Trp, Leu-Trp showed non-competitive inhibition. On the other hand, reversed sequence peptides with Trp at the N-terminal were competitive inhibitors, except Trp-Leu. These results indicate that the sequence of ACE inhibitory dipeptides can affect both inhibitory potency and the inhibition mechanisms.
• Docosahexaenoic acid and eicosapentaenoic acid-enriched phosphatidylcholine liposomes enhance the permeability, transportation and uptake of phospholipids in Caco-2 cells

  Zakir Hossain, Hideyuki Kurihara, Masashi Hosokawa, Koretaro Takahashi

  MOLECULAR AND CELLULAR BIOCHEMISTRY 285 1-2 155 - 163 2006年04月 [査読有り][通常論文]
   

  The influence of docosahexaenoic acid (DHA)- and eicosapentaenoic acid (EPA)-enriched phosphatidylcholine (PC) on the permeability, transport and uptake of phospholipids was evaluated in Caco-2 cells. The cells were grown on permeable polycarbonate transwell filters, thus allowing separate access to the apical and basolateral chambers. The monolayers of the cells were used to measure lucifer yellow permeability and transepithelial electrical resistance (TEER). Transcellular transportation of diphenylhexatriene (DPH) labeled-PC small unilamellar vesicles (SUV) from the apical to basolateral chamber, and uptake of the same SUV was monitored in the cell monolayers. Cell-membrane perturbation was evaluated to measure the release of lactate dehydrogenase and to determine the cell viability with sodium 2-(4-iodophenyl)-3-(4-nitrophenyl) -5-(2, 4-disulfophenyl)-2H-tetrazolium dye reduction assay. The lucifer yellow flux was 1.0 and 1.5 nmol/h/cm(2)with 50 mu M PC, and 17.0 and 23.0 nmol/h/cm(2) with 100 mu M PC when monolayers of Caco-2 cells were treated with DHA- and EPA-enriched PC, respectively. TEER decreased to 24 and 27% with 50 and 100 mu M DHA-enriched PC, and to 25 and 30% with 50 and 100 mu M EPA-enriched PC, respectively. Our results show that DHA- and EPA-enriched PC increases tight junction permeability across the Caco-2 cell monolayer whereas soy PC has no effect on tight junction permeability. Transportation and uptake of DHA- and EPA-enriched PC SUV differed significantly (P < 0.01) from those of soy PC SUV at all doses. We found that PC SUV transported across Caco-2 monolayer and was taken up by Caco-2 cells with very slight injury of the cell membrane up to 100 mu M PC. Lactate dehydrogenase release and cell viability did not differ significantly between the treatment and control, emphasizing that injury was minimal. Our results suggest that DHA- and EPA-enriched PC enhance the permeability, transport and uptake of PC SUV across monolayers of Caco-2 cells.
• Effect of polyunsaturated fatty acid-enriched phosphatidylcholine and phosphatidylserine on butyrate-induced growth inhibition, differentiation and apoptosis in Caco-2 cells

  Z Hossain, M Konishi, M Hosokawa, K Takahashi

  CELL BIOCHEMISTRY AND FUNCTION 24 2 159 - 165 2006年03月 [査読有り][通常論文]
   

  Phospholipids are fascinating in terms of important bio-functional compounds. The present work investigated the effect of polyunsaturated phosphatidylcholine (PC) and phosphatidylserine (PS) on butyrate-induced growth inhibition, differentiation and apoptosis using Caco-2 cells. Growth inhibition of Caco-2 cells became apparent 24 h after addition of PC while it took 48 h with PS. Alkaline phosphatase activity of Caco-2 cells increased with combined PC or PS and sodium butyrate (NaBT) at 72 h, indicating that PC and PS enhanced cell differentiation in the presence of NaBT. An increased enrichment factor was also found when cells were treated with combinations of PC or PS and NaBT. These results suggest that marine PC and PS can be considered to be potentially useful colon cancer chemotherapy agents with high bio-availability. Copyright (c) 2005 John Wiley & Sons, Ltd.
• Production of value added phospholipids via phospholipase A2 mediated bioconversion from soy lysolecithin and docosahexaenoic acid rich free fatty acid mixture.

  Fisheries Sci., 72 909 - 912 2006年 [査読有り][通常論文]
  
• Troglitazone and 9cis, 11trans, 13trans-conjugated linolenic acid: Comparison of their antiproliferative and apoptosis-inducing effects on different colon cancer cell lines

  Y. Yasui, M. Hosokawa, H. Kohno, T. Tanaka, K. Miyashita

  CHEMOTHERAPY 52 5 220 - 225 2006年 [査読有り][通常論文]
   

  Background. We have previously reported that troglitazone, a synthetic ligand for peroxisome proliferator-activated receptor gamma (PPAR gamma), and bitter gourd seed oil rich in 9cis,11trans,13trans-conjugated linolenic acid (9c,11t,13t-CLN) prevent colon carcinogenesis. To evaluate the chemotherapeutic effect and potency of these compounds on colon cancer cells, we investigated their antiproliferative and apoptosis-inducing effects using different human colon cancer cell lines. Methods: The antiproliferative and apoptosis-inducing effects of troglitazone and 9c,11t,13t-CLN were evaluated and compared using HT-29, DILD-11 and Caco-2 cells at different stages of enterocytic differentiation. Results: Troglitazone and 9c,11t,13t-CLN decreased cell viability and induced apoptosis in three colon cancer cell lines. The susceptibility of HT-29, which expresses IPIPAR gamma at high levels, to troglitazone and 9c,11t,13t-CLN was higher than that of Caco-2 cells with low levels of PPAR gamma. Con- clusion:Troglitazone and 9c,11 1 t,13t-CLN exhibited more effective chemotherapeutic effects on HT-29 cells than on Caco-2 cells. Copyright (c) 2006 S. Karger AG, Basel.
• Halocynthiaxanthin and fucoxanthinol isolated from Halocynthia roretzi induce apoptosis in human leukemia, breast and colon cancer cells

  Izumi Konishi, Masashi Hosokawa, Tokutake Sashima, Hidetaka Kobayashi, Kazuo Miyashita

  Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology 142 1-2 53 - 59 2006年01月 [査読有り][通常論文]
   

  The sea squirt Halocynthia roretzi metabolizes fucoxanthin, and subsequently accumulates its derived carotenoids with characteristic structures. In the present study, we isolated halocynthiaxanthin and fucoxanthinol as carotenoids having antiproliferative activity from H. roretzi. Halocynthiaxanthin and fucoxanthinol inhibited the growth of HL-60 human leukemia cells in a dose- and time-dependent manner. Viability of HL-60 treated with 12.5 mu M halocynthiaxanthin and fucoxanthinol was decreased by 12.1% and 5.7% of control after 48 h incubation, respectively. Furthermore, halccynthiaxanthin and fucoxanthinol induced apoptosis in HL-60 cells, MCF-7 human breast cancer cells, and Caco-2 human colon cancer cells. When HL-60 cells were incubated with 12.5 mu M halocynthiaxanthin and fucoxanthinol for 48 h, relative DNA fragmentations were enhanced to 5- and 7-fold compared to that in control cells, respectively. The activities of apoptosis induction by halocynthiaxanthin and fucoxanthinol were higher than that of fucoxanthin which we have previously reported as a carotenoid possessing the ability to induce apoptosis. Facoxanthinol exhibited the highest apoptosis-inducing activity among the three carotenoids. Furthermore, the expression levels of apoptosis-suppressing protein Bcl-2 were decreased in HL-60 cells treated with halocynthiaxanthin and fucoxanthinol. These results suggest that halocynthiaxanthin and fucoxanthinol exhibited potential antiproliferative effects via apoptosis induction in several cancer cell lines. (c) 2005 Elsevier Inc. All right; reserved.
• Occurrence of conjugated fatty acids in aquatic and terrestrial plants and their physiological effects

  Bhaskar Narayan, Masashi Hosokawa, Kazuo Miyashita

  Nutraceutical and Specialty Lipids and their Co-Products 201 - 218 2006年01月01日 

  Conjugated fatty acids are attracting increased interest due to their beneficial effects in terms of human health. Among them conjugated linoleic acid (CLA) has been researched and reviewed extensively in relation to its occurrence1, metabolism, and physiological effects2,3. Several researchers have reported the occurrence of various conjugated fatty acids including trienes, tetraenes, and pentaenes in different plant sources including those from terrestrial and aquatic origins. Attempts to use fatty acid composition as an aid in taxonomical conclusions have also been reviewed thoroughly4,5. The occurrence, health effects, and industrial uses of conjugated dienes, especially CLA/CLA isomers, have also been reviewed extensively and thoroughly by several researchers. Hence, the present chapter covers the conjugated fatty acids other than conjugated dienes including CLA. In the context of this chapter, fatty acids with three or more conjugated double bond systems that occur naturally in plants of terrestrial and aquatic origin are only considered along with their reported/documented physiological effects. For the purpose of this chapter, fatty acids with conjugated unsaturation that also contain acetylenic bonds or oxygen functions are excluded. Also, only macroalgae (sea-grasses) are considered as aquatic plants and the microalgae are excluded. Thus, a comprehensive picture of conjugated fatty acids that occur in plants of terrestrial and aquatic origin with emphasis on their physiological and health effects is provided. It is worth noting that some plant seeds contain conjugated linolenic acid (CLN) at high level (30 to 70 wt% lipid), although other kinds of conjugated fatty acids including CLA are only found in natural products at concentrations less than 1%. Thus, CLN isomers are major conjugated fatty acids of natural origin. Hence, in this chapter, we describe in detail the physiological effects of CLN isomers that occur in some plant seeds. It is hoped that this overview serves as a reference to multidisciplinary researchers working on biochemistry, physiology, and nutrition, especially with reference to conjugated fatty acids.
• Yasui, Y., Hosokawa, M., Sahara, T., Ohgiya, S., Suzuki, R., Kohno, H., Tanaka, T. and Miyashita, K.:"Bitter gourd seed fatty acid rich in 9c,11t,13t-conjugated linolenic acid induces apoptosis and up-regulates the GADD45, p53 and PPAR gamma in human c・・・

  Y Yasui, M Hosokawa, T Sahara, R Suzuki, S Ohgiya, H Kohno, T Tanaka, K Miyashita

  PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS 73 2 113 - 119 2005年08月 [査読有り][通常論文]
   

  Yasui, Y., Hosokawa, M., Sahara, T., Ohgiya, S., Suzuki, R., Kohno, H., Tanaka, T. and Miyashita, K.:"Bitter gourd seed fatty acid rich in 9c,11t,13t-conjugated linolenic acid induces apoptosis and up-regulates the GADD45, p53 and PPAR gamma in human colon cancer Caco-2 cells", Prostaglandins, Leukotrienes & Essential Fatty Acids, 73:113-119(2005)*
• Fucoxanthin from edible seaweed, Undaria pinnatifida, shows antiobesity effect through UCP1 expression in white adipose tissues

  H Maeda, M Hosokawa, T Sashima, K Funayama, K Miyashita

  BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 332 2 392 - 397 2005年07月 [査読有り][通常論文]
   

  Mitochondrial uncoupling protein 1 (UCP1) is usually expressed only in brown adipose tissue (BAT) and a key molecule for metabolic thermogenesis to avoid an excess of fat accumulation. However, there is little BAT in adult humans. Therefore, UCP1 expression in tissues other than BAT is expected to reduce abdominal fat. Here, we show reduction of abdominal white adipose tissue (WAT) weights in rats and mice by feeding lipids from edible seaweed, Undaria pinnatifida. Clear signals of UCP1 protein and mRNA were detected in WAT of mice fed the Undaria lipids, although there is little expression of UCP1 in WAT of mice fed control diet. The Undaria lipids mainly consisted of glycolipids and seaweed carotenoid, fucoxanthin. In the fucoxanthin-fed mice, WAT weight significantly decreased and UCP1 was clearly expressed in the WAT, while there was no difference in WAT weight and little expression of UCP1 in the glycolipids-fed mice. This result indicates that fucoxanthin upregulates the expression of UCP1 in WAT, which may contribute to reducing WAT weight. (C) 2005 Elsevier Inc. All rights reserved.
• Docosahexaenoic acid-containing phosphatidylethanolamine enhances HL-60 cell differentiation by regulation of c-jun and c-myc expression

  H Ishigamori, M Hosokawa, H Kohno, T Tanaka, K Miyashita, K Takahashi

  MOLECULAR AND CELLULAR BIOCHEMISTRY 275 1-2 127 - 133 2005年07月 [査読有り][通常論文]
   

  18:1/docosahexaenoic acid (DHA)-containing phosphatidylethanolamine (PE) enhanced cell differentiation and growth inhibition of HL-60 induced by dibutyryl cAMP (dbcAMP) in a dose-dependent manner. The combined treatment of 200 mu M dbcAMP and 50 mu M 18:1/DHA-PE increased the NBT reducing activity, which is as an indicator of cell differentiation, to more than 75% from 40% of cells treated with 200 mu M dbcAMP alone. In HL-60 cells treated with 50 mu M 18:1/DHA-PE and 200 mu M dbcAMP for 24 h, the expression level of c-jun mRNA and c-Jun protein were remarkably elevated compared to cells treated with dbcAMP alone. In contrast, there was no difference in the expression levels of c-fos mRNA and c-Fos protein between the combination of 18:1/DHA-PE + dbcAMP or dbcAMP alone. On the other hand, the combine treatment of 18:1/DHA-PE and dbcAMP markedly reduced the expression level of c-myc oncogene during 48 h incubation. The decreases of c-myc mRNA by 18:1/DHA-PE and/or dbcAMP was correlated with growth inhibition effect. Thus, 18:1/DHA-PE might enhance dbcAMP-induced HL-60 cell differentiation and growth inhibition by regulation of c-jun and c-myc mRNA and their products.
• Lipid peroxidation of a human hepatoma cell line (HepG2) after incorporation of linoleic acid, arachidonic acid, and docosahexaenoic acid

  M Araseki, H Kobayashi, M Hosokawa, K Miyashita

  BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY 69 3 483 - 490 2005年03月 [査読有り][通常論文]
   

  Lipid peroxidation of human heptoma cell line, HepG2, after incorporation of linoleic acid (LA), arachidonic acid (AA), and docosahexaenoic acid (DHA) was measured with a fluorescent probe and gas chromatography-mass spectrometry (GC-MS) analysis. The analysis with a fluorescent probe showed that incorporation of each polyunsaturated fatty acid (PUFA) enhanced the cellular lipid peroxidation level, but there was little difference in the effect of LA, AA, or DHA on the enhancement of cellular lipid peroxidation. The fluorescent analysis also showed that the addition of H2O2 (0.5 mm) enhanced the cellular lipid peroxidation levels in LA and AA supplemented cells as compared with those without H2O2. However, the enhancement of lipid peroxidation by H2O2 was not observed in DHA-supplemented cells. The same result was obtained in the GC-MS analysis of total amounts of monohydroperoxides (MHP) formed in the cellular phospholipid oxidation. In this case, the main source for MHP was LA in LA-, AA-, and DHA-supplemented cells. A significant amount of AA-MHP and a small amount of DHA-MHP were observed in AA- and DHA-supplemented cells respectively. GC-MS analysis also indicated the specific positional distribution of DHA-MHP isomers. The isomers were formed only by hydrogen abstraction at the C-18 (16-MHP + 20-MHP; 46.5%), C-6 (4-MHP + 8-MHP; 38.5%), and C-12 (10-MHP + 14-MHP; 15.1%) positions, but not at the C-9 or C-15 positions.
• Butyrate-Induced Growth Inhibition and Differentiation in Caco-2 Cells with Hybrid Liposomes

  Zakir Hossain, Hideyuki Kurihara, Masashi Hosokawa, Koretaro Takahashi

  Journal of Oleo Science 54 5 281 - 288 2005年 [査読有り][通常論文]
   

  Hybrid liposomes were prepared by mixing glycerophospholipids with glyceroglycolipids. The effects of hybrid liposomes on Caco-2 cells were investigated. Growth inhibition of cells was determined with sodium 2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2, 4-disulfophenyl)-2H-tetrazolium dye reduction assay. Alkaline phosphatase activity was measured for assessing the cell differentiation induced by sodium butyrate (NaBT). Growth of Caco-2 cells was inhibited at 48 h after addition of all four types hybrid liposomes (PC/DGDG, PC/SQDG, PS/DGDG and PS/SQDG) while at 72 h growth inhibition was significant for all treatments except the hybrid liposome of phosphatidylcholine and digalactosyldiacylglycerol under concentrations of 50 μM glycerophospholipids with 50 μM glyceroglycolipids. Alkaline phosphatase activity of Caco-2 cells increased significantly when cells were treated in combination of hybrid liposomes and NaBT at 72 h, indicating that hybrid liposomes enhanced cell differentiation induced with NaBT. © 2005, Japan Oil Chemists' Society. All rights reserved.
• Araseki, M., Kobayashi, H., Hosokawa, M. and Miyashita. K.:"Lipid peroxidation of a human hepatoma cell line (HepG2) after incorporated linoleic acid, arachidonic acid, and docosahexaenoic acid", Biosci. Biotechnol. Biochem., 69:483-490(2005)*

  2005年 [査読有り][通常論文]
  
• Ishigamori, H., Hosokawa, M., Kohno, H., Tanaka, T., Miyashita, K. and Takahashi, K.:"DHA-containing phosphatidylethanolamine enhances HL-60 cell differentiation through alterations of c-jun and c-myc expression", Mol. Cell. Biochem., 275:127-133(2005)*

  2005年 [査読有り][通常論文]
  
• Growth inhibition and induction of differentiation and apoptosis mediated by sodium butyrate in Caco-2 cells with algal glycolipids

  Z Hossain, H Kurihara, M Hosokawa, K Takahashi

  In vitro Cell & Biology-Animal 41 5-6 154 - 159 2005年 [査読有り][通常論文]
   

  Glycolipids should have potential effects as antitumor agents. However. very few studies have examined this property of digalactosyl diacylglycerol (DGDG) and sulfoquinovosyl diacylglycerol (SQDG) on colon cancer cells. Cell viability was determined every 24 h with sodium 2-(4-iodophenyl)-3-(4 -nitrophenyl)-5-(2, 4-disulfophenyl)-2H-tetrazolium dye reduction assay up to 72 h. Alkaline phosphalase activity was measured for assessing cell differentiation. Apoptosis was tested with enzyme-linked immunosorbent assay analysis. Growth of Caco-2 cells was inhibited apparently at 48 h after addition of SQDG and at 72 h with DGDG. Alkaline phosphalase activity of Caco-2 cells obviously increased in combination with DGDG or SQDG and sodium butyrate (NaBT) at 72 h, indicating that DGDG and SQDG enhanced cell differentiation induced with NaBT. An increased enrichment factor was found when the cell was treated in combination with DGDG or SQDG and NaBT. These results Strongly suggest that DGDG and SQDG should he considered as the leading compounds of potentially useful colon cancer Chemotherapy agents when NaBT is combined.
• Synergistic Effects of Highly Unsaturated Fatty Acid-containing Phosphatidyl-ethanolamine on Differentiation of Human Leukemia HL-60 Cells by Dibutyryl Cyclic Adenosine Monophosphate

  Masashi Hosokawa

  Japanese Journal of Cancer Research 2005年
• Narayan, B., Hosokawa, M. and Miyashita, K.: "Growth inhibition of human pro-myelocytic leukemia (HL-60) cells by lipid extracts of Sargassum marignatum (Fucales, Phaeophyta) harvested off west coast of India with special reference to fatty acid compos・・・

  N Bhaskar, M Hosokawa, K Miyashita

  INDIAN JOURNAL OF MARINE SCIENCES 33 4 355 - 360 2004年12月 [査読有り][通常論文]
   

  Narayan, B., Hosokawa, M. and Miyashita, K.: "Growth inhibition of human pro-myelocytic leukemia (HL-60) cells by lipid extracts of Sargassum marignatum (Fucales, Phaeophyta) harvested off west coast of India with special reference to fatty acid composition", Indian J. Marine Sci., 33:355-360(2004).*
• Fucoxanthin induces apoptosis and enhances the antiproliferative effect of the PPAR gamma ligand, troglitazone, on colon cancer cells

  Masashi Hosokawa

  Biochimica et Biophysica Acta (BBA) - General Subjects 1675 1/3 113 - 119 2004年11月 [査読有り][通常論文]
  
• Fucoxanthin induces apoptosis and enhances the antiproliferative effect of the PPARgamma ligand, troglitazone, on colon cancer cells.

  Hosokawa M, Kudo M, Maeda H, Kohno H, Tanaka T, Miyashita K

  Biochimica et biophysica acta 1675 1-3 113 - 119 2004年11月 [査読有り][通常論文]
  
• Dietary seed oil rich in conjugated linolenic acid from bitter melon inhibits azoxymethane-induced rat colon carcinogenesis through elevation of colonic PPAR gamma expression and alteration of lipid composition

  H Kohno, Y Yasui, R Suzuki, M Hosokawa, K Miyashita, T Tanaka

  INTERNATIONAL JOURNAL OF CANCER 110 6 896 - 901 2004年07月 [査読有り][通常論文]
   

  Our previous short-term experiment demonstrated that seed oil from bitter melon (Momordica charantia) (BMO), which is rich in cis(c)9, trans(t)11, t13-conjugated linolenic acid (CLN), inhibited the development of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF). In our study, the possible inhibitory effect of dietary administration of BMO on the development of colonic neoplasms was investigated using an animal colon carcinogenesis model initiated with a colon carcinogen AOM. Male F344 rats were given subcutaneous injections of AOM (20 mg/kg body weight) once a week for 2 weeks to induce colon neoplasms. They also received diets containing 0.01%, 0.1% or 1% BMO for 32 weeks, starting 1 week before the first dosing of AOM. At the termination of the study (32 weeks), AOM induced 83% incidence (15/18 rats) of colonic adenocarcinoma. Dietary supplementation with 0.01% and 0.1% BMO caused significant reduction in the incidence (47% inhibition by 0.01% BMO, p<0.02; 40% inhibition by 0.1% BMO, p<0.05; and 17% inhibition by 1% BMO) and the multiplicity (64% inhibition by 0.01% BMO, p<0.005; 58% inhibition by 0.1% BMO, p<0.02; and 48% inhibition by 1% BMO, p<0.05) of colonic adenocarcinoma, though a clear dose response was not observed. Such inhibition was associated with the increased content of CLA (c9,t11-18:2)in the lipid composition in colonic mucosa and liver. Also, BMO administration in diet enhanced expression of peroxisome proliferator-activated receptor (PPAR) gamma protein in the non-lesional colonic mucosa. These findings suggest that BMO rich in CLN can suppress AOM-induced colon carcinogenesis and the inhibition might be caused, in part, by modification of lipid composition in the colon and liver and/or increased expression of PPARgamma protein level in the colon mucosa. (C) 2004 Wiley-Liss, Inc.
• Pomegranate seed oil rich in conjugated linolenic acid suppresses chemically induced colon carcinogenesis in rats

  H Kohno, R Suzuki, Y Yasui, M Hosokawa, K Miyashita, T Tanaka

  CANCER SCIENCE 95 6 481 - 486 2004年06月 [査読有り][通常論文]
   

  Pomegranate (Punica granatum L.) seed oil (PGO) contains more than 70% cis(c),trans(t)11, c13-18:3 as conjugated linolenic acids (CLN). Our previous short-term experiment demonstrated that seed oil from bitter melon (Momordica charantia) (BMO), which is rich in c9, t11, t13-CLN, inhibited the occurrence of colonic aberrant crypt foci (ACF) induced by azoxymethane (AOM). In this study, we investigated the effect of dietary PGO on the development of AOM-induced colonic malignancies and compared it with that of conjugated linoleic acid (CLA). To induce colonic tumors, 6-week old male F344 rats were given subcutaneous injections of AOM (20 mg/kg body weight) once a week for 2 weeks. One week before the AOM treatment they were started on diet containing 0.01%, 0.1%, or 1% PGO or 1% CLA for 32 weeks. Upon termination of the bioassay (32 weeks) colon tumors were evaluated histopathologically. AOM exposure produced colonic adenocarcinoma with an incidence of 81% and multiplicity of 1.88 +/- 1.54 at week 32. Administration of PGO in the diet significantly inhibited the incidence (AOM + 0.01% PGO, 44%, P < 0.05; AOM + 0.1% PGO, 38%, P < 0.01; AOM + 1% PGO, 56%) and the multiplicity (AOM + 0.01% PGO, 0.56 +/- 0.73, P < 0.01; AOM + 0.1% PGO, 0.50 +/- 0.73, P < 0.005; AOM + 1% PGO, 0.88 +/- 0.96, P < 0.05) of colonic adenocarcinomas, although a clear dose-response relationship was not observed at these dose levels. CLA feeding also slightly, but not significantly, reduced the incidence and multiplicity of colonic adenocarcinomas. The inhibition of colonic tumors by PGO was associated with an increased content of CLA (c9, t11, 18:2) in the lipid fraction of colonic mucosa and liver. Also, administration of PGO in the diet elevated expression of peroxisome proliferator-activated receptor (PPAR) gamma protein in the non-tumor mucosa. These results suggest that PGO rich in c9, t11, c13-CLN can suppress AOM-induced colon carcinogenesis, and the inhibition is associated in part with the increased content of CLA in the colon and liver and/or increased expression of PPARgamma protein in the colon mucosa.
• Separation of sardine oil without heating from surimi waste and its effect on lipid metabolism in rats

  K Toyoshima, R Noguchi, M Hosokawa, K Fukunaga, T Nishiyama, R Takahashi, K Miyashita

  JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 52 8 2372 - 2375 2004年04月 [査読有り][通常論文]
   

  Sardine oil was obtained by centrifugation of surimi wastewater without heating or chemical refining. This oil (CE) showed light yellow color and the peroxide value was less than 1.0 meq/kg. The main lipid class of CE was triacylglycerol (TG) (> 99%). These features indicate that CE can be directly used as food materials without further purification. Commercial sardine oil (CO) is usually prepared via some kind of refining process with high temperature (250 C) and chemical treatment. The comparative study on the physiological effects of these sardine oils (CE and CO) revealed that the dietary sardine oils were more effective in reducing abdominal fat pads, plasma total cholesterol, and TG levels of rats than was a soybean oil diet (control). Furthermore, these effects were greater in CE than CO, although there was little difference in the fatty acid composition of both oils. Although the main lipid class of CE was TG (> 99%), CE was prepared by centrifugation from surimi waste and directly used as dietary fat without further purification. Therefore, CE may contain some kinds of minor components, which could be attributed to the higher physiological activity of CE. To reveal the involvement of the minor compounds in CE, we prepared TG from CE by column chromatography and measured its effect on lipid metabolism of rats. TG from CE also showed the reducing effects on abdominal fad pads and plasma lipid levels. The effect of TG from CE was almost the same as that of original CE, suggesting that the higher nutritional activity of CE than CO may not be due to the minor compounds in CE.
• Bioconversion of n-3 and n-6 PUFA by Clavibacter sp ALA2

  M Hosokawa, CT Hou, D Weisleder

  JOURNAL OF THE AMERICAN OIL CHEMISTS SOCIETY 80 11 1085 - 1091 2003年11月 [査読有り][通常論文]
   

  Clavibacter sp. ALA2 oxidized n-3 and n-6 PUFA into a variety of oxylipins. Structures of products converted from EPA and DHA were determined as 15,18-dihydroxy-14,17-epoxy-5(Z),8(Z),11(Z)-eicosatrienoic acid and 17,20-dihydroxy-16,19-epoxy-4(Z),7(Z),10(Z),13(Z)-docosatetraenoic acid by GC-MS and NMR analyses. In contrast, gamma-linolenic acid and arachidonic acid were converted to diepoxy bicyclic FA, tetrahydrofuranyl monohydroxy FA, and trihydroxy FA. Thus, the structures of bioconversion products were different between n-3 and n-6 PUFA. Furthermore, strain ALA2 placed hydroxy groups and cyclic structures at the same position from the omega-terminal despite the number of carbons in the chain and the double bonds in the PUFA.
• Biosynthesis of tetrahydrofuranyl fatty acids from linoleic acid by Clavibacter sp ALA2

  M Hosokawa, CT Hou, D Weisleder, W Brown

  JOURNAL OF THE AMERICAN OIL CHEMISTS SOCIETY 80 2 145 - 149 2003年02月 [査読有り][通常論文]
   

  Clavibacter sp, ALA2 converts linoleic acid into many novel oxygenated products including hydroxy FA and tetrahydrofuranyl unsaturated FA (THFA). One of them was tentatively identified by CC-MS as 12,13,16-trihydroxy-9(Z)-oc-tadecenoic acid (12,13,16-THOA) (Hou, C.T., H.W. Gardner, and W. Brown, J Am. Oil Chem. Soc. 78:1167-1169, 2001). We have separated and purified 12,13,1 6-THOA from its isomer, 12,13,17-THOA, by silica gel column chromatography and by preparative TLC. Its structure was then confirmed by proton and C-13 NMR analyses, Purified 12,13,1 6-THOA was used as a substrate to study the biosynthesis of THFA. Within 24 h of incubation, cells of strain ALA2 converted 12,13,1 6-THOA to both 12-hydroxy-13,16-epoxy-9(Z)-octadecenoic acid (12-hydroxy-THFA) and 7,12-dihydroxy-13,16-epoxy-9(Z)-octadecenoic acid (7,12-dihydroxy-THFA). The relative abundance of 7,12-dihydroxy-THFA increased with incubation time, whereas that of 12,13,1 6-THOA and of 12-hydroxy-THFA decreased. Therefore, the biosynthetic pathway of THFA from linoleic acid by strain ALA2 is as follows: linoleic acid --> 12,13-dihydroxy-9(Z)-octadecenoic acid --> 12,13,16-THOA --> 12-hydroxy-THFA --> 7,12-dihydroxy-THFA.
• Ono, S., Hosokawa, M., Miyashita, K. and Takahashi, K.:"Isolation of peptides with angiotensin I-converting enzyme inhibitory effect derived from hydrolysate of upstream chum salmon muscle", J. Food Sci., 68:1611-1614(2003)*

  S Ono, M Hosokawa, K Miyashita, K Takahashi

  JOURNAL OF FOOD SCIENCE 68 5 1611 - 1614 2003年 [査読有り][通常論文]
   

  In order to utilize upstream chum salmon as a component of nutraceutical food, their defatted muscle proteins were hydrolyzed with 5% thermolysin. The resulting hydrolysate showed high inhibitory activity against angiotensin I-converting enzyme (inhibitory concentration(50) = 27.9 protein mug/mL) in vitro. A significant reduction of systolic blood pressure was observed when 500 and 2000 mg/kg of body weight were orally administered into spontaneously hypertensive rats. Angiotensin I-converting enzyme inhibitory peptides contained in the hydrolysate were isolated with various chromatographs. These 6 active peptides were Trp residue-containing dipeptides: Trp-Ala, Val-Trp, Trp-Met, Met-Trp, Ile-Trp, and Leu-Trp. The inhibitory concentration(50) values of these dipeptides ranged from 2.5 muM to 277.3 muM.
• Hosokawa, M., Hou, C.T., Weisleder, W. and Brown, W.:"Isolation and structure determination of 12,13,16-trihydroxy-9(Z)-octadecenoic acid produced from linoleic acid by Clavibacter sp. ALA2 and biosynthesis of tetrahydrofuranyl fatty acids", J. Am. Oi・・・

  2003年 [査読有り][通常論文]
   

  Hosokawa, M., Hou, C.T., Weisleder, W. and Brown, W.:"Isolation and structure determination of 12,13,16-trihydroxy-9(Z)-octadecenoic acid produced from linoleic acid by Clavibacter sp. ALA2 and biosynthesis of tetrahydrofuranyl fatty acids", J. Am. Oil Chem. Soc., 80:145-149(2003)*
• Hosokawa, M., Hou, C.T. and Weisleder, D.:"Bioconversion products from n-3 and n-6 polyunsaturated fatty acids by Clavibacter sp. ALA2", J. Am. Oil. Chem. Soc., 80:1085-1091(2003)*

  2003年 [査読有り][通常論文]
  
• Hosokawa, M., Hou, C.T. and and Weisleder, W.:"Production of novel tetrahydrofuranyl fatty acids from alpha-linolenic acid by Clavibacter sp. ALA2", Appl. Environ Microbiol., 69:3868-3873(2003)*

  M Hosokawa, CT Hou, D Weisleder

  APPLIED AND ENVIRONMENTAL MICROBIOLOGY 69 7 3868 - 3873 2003年 [査読有り][通常論文]
   

  Previously, it was reported that a newly isolated microbial culture, Clavibacter sp. strain ALA2, produced trillydroxy unsaturated fatty acids, diepxoy bicyclic fatty acids, and tetrabydroxyfuranyl fatty acids (THFAs) from linoleic acid (C. T. Hou, J. Am. Oil Chem. Soc. 73:1359-1362,1996; C. T. Hou. and R. J. Forman III, J. Ind. Microbiol. Biotechnol. 24:275-276, 2000; C. T. Hou, H. Gardner, and W. Brown, J. Am. Oil Chem. Soc. 75:14831487,1998; C. T. Hou, H. W. Gardner, and W. Brown, J. Am. Oil Chem. Soc. 78:1167-1169,2001). In this study, we found that Clavibacter sp. strain ALA2 produced novel THFAs, including 13,16-dihydroxy-12-THFA, 15epoxy-9(Z)-octadecenoic acid (13,16-dihydroxy-THFA), and 7,13,16-trihydroxy-12, 15-epoxy-9(Z)-octadecenoic acid (7,13,16-trihydroxy-THFA), from alpha-linolenic acid (9,12,15-octadecatrienoic acid). The chemical structures of these products were determined by gas chromatography-mass spectrometry and proton and C-13 nuclear magnetic resonance analyses. The optimum incubation temperature was 30degreesC for production of both hydroxy-THFAs. 13,16-Dihydroxy-THFA was detected after 2 days of incubation, and the concentration reached 45 mg/50 ml after 7 days of incubation; 7,13,16-trihydroxy-THFA was not detected after 2 days of incubation, but the concentration reached 9 mg/50 ml after 7 days of incubation. The total yield of both 13,16-dihydroxy-THFA and 7,13,16-trihydroxy-THFA was 67% (wt/wt) after 7 days of incubation at 30'C and 200 rpm. In previous studies, it was reported that Clavibacter sp. strain ALA2 oxidized the C-7, C-12, C-13, C-16, and C-17 positions of linoleic acid (n-6) into hydroxy groups. In this case, the bond between the C-16 and C-17 carbon atoms is saturated. In ot-linolenic acid (n-3), however, the bond between the C-16 and C-17 carbon atoms is unsaturated. It seems that enzymes of strain ALA2 oxidized the C-12-C-13 and C-16-C-17 double bonds into dihydroxy groups first and then converted them to hydroxy-THFAs.
• Dual action of isoprenols from herbal medicines on both PPAR gamma and PPAR alpha in 3T3-L1 adipocytes and HepG2 hepatocytes

  N Takahashi, T Kawada, T Goto, T Yamamoto, A Taimatsu, N Matsui, K Kimura, M Saito, M Hosokawa, K Miyashita, T Fushiki

  FEBS LETTERS 514 2-3 315 - 322 2002年03月 [査読有り][通常論文]
   

  Several herbal medicines improve hyperlipidemia, diabetes and cardiovascular diseases. However, the molecular mechanism underlying this improvement has not yet been clarified. In this study, we found that several isoprenols, common components of herbal plants, activate human peroxisome proliferator-activated receptors (PPARs) as determined using the novel GAL4 ligand-binding domain chimera assay system with coactivator coexpression. Farnesol and geranylgeraniol that are typical isoprenols in herbs and fruits activated not only PPARgamma but also PPARalpha as determined using the chimera assay system. These compounds also activated full-length human PPARgamma and PPARalpha in CV1 cells. Moreover, these isoprenols upregulated the expression of some lipid metabolic target genes of PPARgamma and PPARalpha in 3T3-L1 adipocytes and HepG2 hepatocytes, respectively. These results suggest that herbal medicines containing isoprenols with dual action on both PPARgamma and PPARalpha can be of interest for the amelioration of lipid metabolic disorders associated with diabetes. (C) 2002 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.
• Takahashi, N., Kawada, T., Gotoh, T., Yamamoto, T., Taimatsu, A., Matsui, N., Kimura, K., Saitoh, M. Hosokawa, M., Miyashita, K. and Fushiki, T. "Dual action of isoprenols from herbal medicines on both PPAR and PPAR g in 3T3-L1 adipocytes and HepG2 he・・・

  2002年 [査読有り][通常論文]
   

  Takahashi, N., Kawada, T., Gotoh, T., Yamamoto, T., Taimatsu, A., Matsui, N., Kimura, K., Saitoh, M. Hosokawa, M., Miyashita, K. and Fushiki, T. "Dual action of isoprenols from herbal medicines on both PPAR and PPAR g in 3T3-L1 adipocytes and HepG2 hepatocytes". FEBS Lett., 514: 315-322(2002) *
• 「スルメイカ肝膵臓ならびに遡上シロサケのプロテアーゼ加水分解によるアンジオテンシンI変換酵素阻害ペプチドへの変換」

  小野世吾, 細川雅史, 井上明, 山田大介, 高橋是太郎

  日本水産学会誌 68 2 192 - 196 公益社団法人日本水産学会 2002年 [査読有り][通常論文]
   

  北海道において水産廃棄物として多量に排出されているスルメイカ肝膵臓や遡上シロサケを有効に利用するため,アンジオテンシンI変換酵素(ACE)阻害ペプチドへの変換を試みた。種々のプロテアーゼによる加水分解物は,ACEに対し阻害活性を示した。特に,シロサケ脱脂粉末に対してサーモリシンを5%添加し,37℃で2時間反応を行うことにより86.9%の収率で分解物が得られ,そのACE阻害活性は終濃度78.9μg/mLで73.0%に達した。
• Kohno, H., Suzuki, R., Noguchi, R., Hosokawa, M., Miyashita, K. and Tanaka, T.: "Dietary conjugated linolenic acid inhibits azoxymethane-induced colonic aberrant crypt foci in rats", Jpn. J. Cancer Res., 93:133-42(2002) *

  H Kohno, R Suzuki, R Noguchi, M Hosokawa, K Miyashita, T Tanaka

  JAPANESE JOURNAL OF CANCER RESEARCH 93 2 133 - 142 2002年 [査読有り][通常論文]
   

  The modifying effects of dietary feeding of conjugated linolenic acid (CLN) isolated from the seeds of bitter gourd (Momordica charantia) on the development of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) were investigated in male F344 rats to predict its possible cancer chemopreventive efficacy. The effect of CLN on the proliferating cell nuclear antigen (PCNA) index in colonic ACF was also examined. Rats were given subcutaneous injections of AOM (20 mg/kg body weight) once a week for 2 weeks to induce ACE They also received the experimental diet containing 0.01%, 0.1% or 1% CLN for 5 weeks, starting one week before the first dosing of AOM. AOM exposure produced a substantial number of ACF (108 +/- 21/rat) at the end of the study (week 4). Dietary administration of CLN caused a significant reduction in the frequency of ACF: 87 +/- 14 (19.4% reduction, P<0.05) at a dose of 0.01%, 69 +/- 28 (36.1% reduction, P<0.01) at a dose of 0.1% and 40 +/- 6 (63.0% reduction, P<0.001) at a dose of 1%. Also, CLN administration lowered the PCNA index and induced apoptosis in ACE These findings might suggest possible chemopreventive activity of CLN in the early phase of colon tumorigenesis through modulation of cryptal cell proliferation activity and/or apoptosis.
• Liposomal sn-2 DHA inserted phospholipid decreases tumor size of fibrosarcoma

  Akihito Fujimoto, Jin-Ichi Sasaki, Masashi Hosokawa, Koretaro Takahashi

  Fisheries Science 68 1639 - 1640 2002年 [査読有り][通常論文]
  
• Dietary effects of bitter gourd oil on blood and liver lipids of rats

  R Noguchi, Y Yasui, R Suzuki, M Hosokawa, K Fukunaga, K Miyashita

  ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS 396 2 207 - 212 2001年12月 [査読有り][通常論文]
   

  Bitter gourd is widely used as an edible plant in Asia. In this study, we evaluated the effects of bitter gourd oil (BGO) on the blood and liver lipids of rats. Three groups of rats were given a basal diet (AIN-93G) containing 7% fat by weight. The dietary fat consisted of soybean oil (control), soybean oil + BGO (6.5:0.5, w/w; 0.5% BGO), or soybean oil + BGO (5:2, w/w; 2.0% BGO). This fat treatment gave 3.4 and 15.4% of cis(c)9,trans(t)11,t13-18:3 in the dietary fat of 0.5 and 2.0% BGO, respectively. Fatty acid analysis showed the occurrence of c9,t11-18:2 in the liver of rats fed BGO diets, whereas this conjugated linoleic acid (CLA) isomer was not detected in the liver of rats fed the control diet. Furthermore, dietary BGO decreased the concentration of 18:2n-6 and increased the concentration of 22:6n-3. The formation of the CLA isomer in the liver lipids of rats fed BGO diets could be explained by either of the following two metabolic pathways, namely, enzymatic biohydrogenation of c9,t11,t13-18:3 or enzymatic isomerization of c9,c12-18:2. The BGO diets had significantly reduced free cholesterol levels with a trend toward an increase in HDL cholesterol, but there was no significant change in the total cholesterol. The dietary BGO also affected the level of plasma hydroperoxides. A slight but significant increase in hydroperoxides was found in the rats fed 2.0% BGO. This may be attributed to the lower oxidative stability of c9,t11,t13-18:3 in BGO. (C) 2001 Elsevier Science.
• Ligands for peroxisome proliferator-activated receptors α and γ inhibit chemically induced colitis and formation of aberrant crypt foci in rats

  T. Tanaka, H. Kohno, S.-I. Yoshitani, S. Takashima, A. Okumura, A. Murakami, M. Hosokawa

  Cancer Research 61 6 2424 - 2428 2001年03月 [査読有り][通常論文]
   

  The biological role of the peroxisome proliferator-activated receptors (PPARs) in various diseases, including inflammation and cancer, has been highlighted recently. Although PPAR gamma ligands have been found to inhibit mammary carcinogenesis in rodents, the effects on colon tumorigenesis are controversial. In the present study, three different experiments were conducted to investigate the modifying effects of PPARs ligands (PPAR alpha and PPAR gamma) on colitis and an early phase of colitis-related colon carcinogenesis in male F344 rats. In the first experiment, gastric gavage of troglitazone (PPAR gamma ligand, 10 or 100 mg/kg body weight) or bezafibrate (PPAR alpha ligand, 10 or 100 mg/kg body weight) inhibited colitis induced by dextran sodium sulfate (DSS) and lowered trefoil factor-2 content in colonic mucosa. In the second experiment, dietary administration (0.01 or 0.05% in diet) of troglitazone and bezafibrate for 4 weeks significantly reduced azoxymethane (AOM, two weekly s.c. injections, 20 mg/kg body weight)-induced formation of aberrant crypts foci, which are precursor lesions for colon carcinoma. In the third experiment, dietary administration (0.01% in diet for 6 weeks) of pioglitazone (PPAR gamma ligand), troglitazone, and bezafibrate effectively suppressed DSS/AOM-induced ACF. Administration of both ligands significantly reduced cell proliferation activity in colonic mucosa exposed to DSS and AOM. Our results suggest that synthetic PPARs ligands (PPAR alpha and PPAR gamma) can inhibit the early stages of colon tumorigenesis with or without colitis.
• Kohno, H., Yoshitani, S. Takashima, S., Okumura, A., Hosokawa, M. and Yamaguchi, M., Tanaka, T. : “Troglitazone, a ligand for peroxisome proliferator-activated receptor γ, inhibits chemically-induced aberrant cript foci in rats”, Jpn. J. Cancer Res. 92・・・

  2001年 [査読有り][通常論文]
   

  Kohno, H., Yoshitani, S. Takashima, S., Okumura, A., Hosokawa, M. and Yamaguchi, M., Tanaka, T. : “Troglitazone, a ligand for peroxisome proliferator-activated receptor γ, inhibits chemically-induced aberrant cript foci in rats”, Jpn. J. Cancer Res. 92: 396-403 (2001)
• Hosokawa, M., Sato, A., Ishigamori, H., Kohno, H., Tanaka, T. and Takahashi, T.: “Synergistic effects of highly unsaturated fatty acid-containing phosphatidylethanolamine on differentiation of human leukemia HL-60 cells by dibutyryl cyclic adenosine mo・・・

  M Hosokawa, A Sato, H Ishigamori, H Kohno, T Tanaka, K Takahashi

  JAPANESE JOURNAL OF CANCER RESEARCH 92 6 666 - 672 2001年 [査読有り][通常論文]
   

  Hosokawa, M., Sato, A., Ishigamori, H., Kohno, H., Tanaka, T. and Takahashi, T.: “Synergistic effects of highly unsaturated fatty acid-containing phosphatidylethanolamine on differentiation of human leukemia HL-60 cells by dibutyryl cyclic adenosine monophosphate”, Jpn. J. Cancer Res. 92： 666-672 (2001)*
• Noguchi, R., Yasui, Y., Suzuki, R., Hosokawa, M., Fukunaga, K. and Miyashita, K.: “Dietary effect of bitter gourd oil on blood and liver lipids of rats”, Arch. Biochem. Biophys, 396: 207-212 (2001)

  2001年 [査読有り][通常論文]
  
• Troglitazone, a ligand for peroxisome proliferator-activated receptor γ, inhibits chemically-induced aberrant crypt foci in rats

  Hiroyuki Kohno, Shin-Ichiro Yoshitani, Shigeki Takashima, Ataru Okumura, Masashi Hosokawa, Nobuo Yamaguchi, Takuji Tanaka

  Japanese Journal of Cancer Research 92 4 396 - 403 2001年 [査読有り][通常論文]
   

  The biological roles of peroxisome proliferator-activated receptors (PPARs) in various diseases, including inflammation and cancer, have been highlighted recently. Although PPARγ ligand is suspected to play an important role in carcinogenesis, its effects on colon tumorigenesis remain undetermined. The present time-course study was conducted to investigate possible modifying effects of a PPARγ ligand, troglitazone, on the development and growth of aberrant crypt foci (ACF), putative precursor lesions for colon carcinoma, induced by azoxymethane (AOM) or dextran sodium sulfate (DSS) in male F344 rats. Oral troglitazone (10 or 30 mg/kg body weight (b.w.)) significantly reduced AOM (two weekly subcutaneous injections, 20 mg/kg b.w.)-induced ACF. Treatment with troglitazone increased apoptosis and decreased polyamine content and ornithine decarboxylase (ODC) activity in the colonic mucosa of rats treated with AOM. Gastric gavage of troglitazone also inhibited colitis and ACF induced by DSS (1% in drinking water), in conjunction with increased apoptosis and reduced colonic mucosal polyamine level and ODC activity. Our results suggest that troglitazone, a synthetic PPARγ ligand, can inhibit the early stage of colon tumorigenesis with or without colitis.
• Production of tailor-made polyunsaturated phospholipids through bioconversions

  K Takahashi, M Hosokawa

  JOURNAL OF LIPOSOME RESEARCH 11 4 343 - 353 2001年 [査読有り][通常論文]
  
• Hosokawa,M.,Shimatani,T.,Kaneda,T.,Inoue Y.and Takahashi K.:“Coversion to Docosahexaenoic Acid-Containing Phosphatidylserine from Squid Skin Lecithin by Phospholipase D-Mediated Transphosphatidylation”,Journal of Agricultural and Food Chemistry, 48:455・・・

  2000年 [査読有り][通常論文]
   

  Hosokawa,M.,Shimatani,T.,Kaneda,T.,Inoue Y.and Takahashi K.:“Coversion to Docosahexaenoic Acid-Containing Phosphatidylserine from Squid Skin Lecithin by Phospholipase D-Mediated Transphosphatidylation”,Journal of Agricultural and Food Chemistry, 48:4550-4554(2000)※
• Conversion to docosahexaenoic acid-containing phosphatidylserine from squid skin lecithin by phospholipase D-mediated transphosphatidylation

  Masashi Hosokawa

  Journal of Agricultural and Food Chemistry 2000年
• Antibacterial activity against cariogenic bacteria and inhibition of insoluble glucan production by free fatty acids obtained from dried Gloiopeltis furcata

  H Kurihara, Y Goto, H Aida, M Hosokawa, K Takahashi

  FISHERIES SCIENCE 65 1 129 - 132 1999年02月 [査読有り][通常論文]
   

  Antibacterial substance for mutans streptococci was obtained from dried Gloiopeltis furcata by chromatographic separation. The substance was determined to be a mixture of free fatty acids (FFAs), from the results of instrumental analyses. The FFAs obtained showed moderate antibacterial activity against mutans streptococci, with minimal inhibitory concentration values between 25 and 50 mu g/ml. These FFAs also inhibited insoluble glucan production catalyzed by glucosyltransferase of Streptococcus sobrinus. Experiments carried out by using commercially available fatty acids indicated that unsaturated fatty acids showed more potent inhibition against insoluble glucan production than saturated fatty acids.
• リパーゼによる高度不飽和アシルグリセリン混合物の内部エステル交換反応

  細川 雅史, 堀井 亜希, 高橋 是太郎

  日本油化学会誌 = Journal of Japan Oil Chemists' Society 48 1 51 - 53 日本油化学会 = Japan Oil Chemists' Society 1999年01月20日 [査読有り][通常論文]
   

  The triacylglycerol (TG) molar ratio was augmented by Lipozyme IM-mediated interesterification of docosahexaenoic acid (DHA) rich (72.0%) partial acylglycerol mixtures (DHA-70G). DHA-70G used as substrate contained TG at 49.3%. Through interesterification mediated by Lipozyme IM previously dried with phosphoric anhydride prior to reaction, TG increased to 64.5% by 24 h. The addition of molecular sieves in the reaction system at this point was effective by further increased TG in the reaction product. This content finally reached 81.0% at 48 h interesterification. DHA content dominated for 7...
• Toda,H.,Kurihara,H.,Hosokawa,M. and Takahashi,K.:"Inhibition of α-glucuronidase by purine nucleotides",Fisheries Sci.,65:667-668(1999)*

  1999年 [査読有り][通常論文]
  
• Hosokawa,M.,Wanezaki,S.,Miyauchi,K.,Kurihara,H.,Kohno,H.,Kawabata,J.,Odashima, S, and Takahashi,K.:"Apoptosis-inducing effect of fucoxanthin on human leukemia cell line HL-60",Food Sci.Technol.Res.,5:243-246(1999)*

  1999年 [査読有り][通常論文]
  
• Hosokawa,M.,Minami,K.,Kohno,H.,Tanaka,Y. and Hibino,H.:"Differentiation- and apoptosis-inducing activities of phospholipids containing docosahexaenoic acid for mouse myeloid leukemia M1 cells",Fisheries Sci.,65:798-799 (1999)*

  HOSOKAWA Masashi, MINAMI Keiichi, KOHNO Hiroyuki, TANAKA Yukihisa, HIBINO Hidehiko

  Fisheries science : FS 65 5 798 - 799 1999年 [査読有り][通常論文]
  
• Inhibition of β-Glucuronidase by Purine Nucleotides

  Masashi Hosokawa

  Fisheries Science 65 4 667 - 668 1999年 [査読有り]
  
• Apoptosis-Inducing Effect of Fucoxanthin on Human Leukemia Cell Line HL-60.

  Masashi HOSOKAWA, Satoshi WANEZAKI, Kozue MIYAUCHI, Hideyuki KURIHARA, Hiroyuki KOHNO, Jun KAWABATA, Shizuo ODASHIMA, Koretaro TAKAHASHI

  Food Science and Technology Research 5 3 243 - 246 1999年 [査読有り]
  
• Preparation of highly unsaturated fatty acid-containing phosphatidylcholine by transesterification with phospholipase A(2)

  M Hosokawa, M Ito, K Takahashi

  BIOTECHNOLOGY TECHNIQUES 12 8 583 - 586 1998年08月 [査読有り][通常論文]
   

  To prepare phospholipids containing highly unsaturated fatty acids (HUFA) by a one-step enzymatic reaction, 14 mu mol soy phosphatidylcholine (soy PC) in combination with 60 mu mol HUFA as acyl donor were transesterified with porcine pancreatic phospholipase A(2). Specify HUFA was successively incorporated into the sn-2 position of soy PC by this reaction at greater than 70% of total fatty acids at sn-2.
• Hosokawa,M.,Ito,M and Takahashi,K.:"Preparation of highly unsaturated fatty acid-containing phosphatidylcholine by transesterification with phospholipase A2",Biotechnol.Tech.,12:583-586(1998)*

  1998年 [査読有り][通常論文]
  
• Hosokawa,M.,Ono,M.,Takahashi,K. and Inoue,K.:"Increase in deformability of human erythrocytes through the action of beta-lysophospholipid rich in n-3 poly unsaturated fatty acid content", J. Jpn. Oil Chem. Soc., 47:1313-1318 (1998)*

  細川 雅史, 小野 雅代, 高橋 是太郎, 井上 良計

  Journal of Japan Oil Chemists' Society 47 12 1313 - 1318,1360 Japan Oil Chemists' Society 1998年 [査読有り][通常論文]
   

  Lysophosphatidylcholine (LPC) that binds to docosahexaenoic acid (DHA) at the <I>sn</I>-2 position (β-DHA-LPC) was prepared by the Lipozyme mediated selective partial hydrolysis of DHA-enriched egg yolk lecithin. The β-DHA-LPC was found to be rapidly incorporated into erythrocyte cells and increase their deformability at 5μM/erythrocyte.
• Water activity-adjusted enzymatic partial hydrolysis of phospholipids to concentrate polyunsaturated fatty acids

  M Ono, M Hosokawa, Y Inoue, K Takahashi

  JOURNAL OF THE AMERICAN OIL CHEMISTS SOCIETY 74 11 1415 - 1417 1997年11月 [査読有り][通常論文]
   

  Selective partial hydrolyses of egg yolk phospholipid and squid skin phospholipid were carried out. By keeping the water activity (a(W)) of Lipozyme IM at an intermediate level, it was easy to concentrate docosahexaenoic acid (DHA). II was also possible to concentrate both DHA and arachidonic acid (AA) simultaneously to a certain level under this a(W) range. However, it was impossible to concentrate AA alone when DHA was present. Though there is a limitation in concentrating AA exclusively, the proposed a(W)-adjusted hydrolytic reaction is a promising way for preparing phospholipids rich in DHA.
• Tochizawa, K., Hosokawa, M., Kurihara, H., Kohno, H., Odashima, S. and Takahashi, K. : "Effects of Phospholipids Containing Docosahexaenoic Acid on Differentiation and Growth of HL-60 Human Promyelocytic Leukemia Cells", J. Jpn. Oil Chem. Soc., 46 : 38・・・

  栃澤 馨, 細川 雅史, 栗原 秀幸, 甲野 裕之, 小田島 粛夫, 高橋 是太郎

  Journal of Japan Oil Chemists' Society 46 4 383 - 390,457 Japan Oil Chemists' Society 1997年 [査読有り][通常論文]
   

  Tochizawa, K., Hosokawa, M., Kurihara, H., Kohno, H., Odashima, S. and Takahashi, K. : "Effects of Phospholipids Containing Docosahexaenoic Acid on Differentiation and Growth of HL-60 Human Promyelocytic Leukemia Cells", J. Jpn. Oil Chem. Soc., 46 : 383-390 (1997)＊
• Ono, M., Hosokawa, M., Inoue, Y. and Takahashi, K. : "Water Activity Adjusted Enzymatic Partial Hydrolysis of Phospholipids to Concentrate Polyunsaturated Fatty Acids", J. Am. Oil Chem. Soc., 74 : 1415-1417 (1997)＊

  1997年 [査読有り][通常論文]
  
• Ono, M., Hosokawa, M., Inoue, Y. and Takahashi, K. : "Concentration of Docosahexaenoic Acid-Containing Phospholipids through Lipozyme IM-Mediated Hydrolysis", J. Jpn. Oil Chem. Soc., 46 : 867-872 (1997)＊

  1997年 [査読有り][通常論文]
  
• PREPARATION OF THERAPEUTIC PHOSPHOLIPIDS THROUGH PORCINE PANCREATIC PHOSPHOLIPASE A(2)-MEDIATED ESTERIFICATION AND LIPOZYME-MEDIATED ACIDOLYSIS

  M HOSOKAWA, K TAKAHASHI, Y KIKUCHI, M HATANO

  JOURNAL OF THE AMERICAN OIL CHEMISTS SOCIETY 72 11 1287 - 1291 1995年11月 [査読有り][通常論文]
   

  Highly unsaturated fatty acid-containing phospholipids (HUFA-PL), which serve to increase the deformability of human red blood cells, were prepared through porcine phospholipase A(2)-mediated esterification of the lysophosphatidylcholone, which was derived from soy phosphatidylcholine (PC), and by Lipozyme-mediated acidolysis. Through these processes, phospholipase A(2), with formamide as a water mimic, enhanced the incorporation of HUFA into position sn-2 of PC and suppressed hydrolysis of the synthesized PL. On the other hand, Lipozyme-mediated acidolysis between position sn-1 of soy PC and HUFA was enhanced by a combination of water and propylene glycol. Simultaneously, the recovered PL products showed decreased hydrolysis of newly synthesized health-beneficial HUFA-PL.
• APPLICATION OF WATER MIMICS ON PREPARATION OF EICOSAPENTAENOIC AND DOCOSAHEXAENOIC ACIDS CONTAINING GLYCEROLIPIDS

  M HOSOKAWA, K TAKAHASHI, N MIYAZAKI, K OKAMURA, M HATANO

  JOURNAL OF THE AMERICAN OIL CHEMISTS SOCIETY 72 4 421 - 425 1995年04月 [査読有り][通常論文]
   

  To obtain enhanced incorporation of highly unsaturated fatty acids and recovery of glycerolipid products, organic solvents with high dielectric constants (water mimics) were substituted for part of the essential water for lipase activation to study their effect on acidolysis and transesterification. In acidolysis/transesterification of fish oil triglycerides and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), Lipozyme IM-60 with ethylene glycol as a water mimic enhanced the incorporation of EPA and suppressed the hydrolysis of synthesized glycerolipid. On the other hand, transesterification between soy phosphatidylcholine and EPA was enhanced by a water and propylene glycol combination. In a nonaqueous medium that contained appropriate amounts of water and organic solvents (water mimics), Lipozyme IM-60 increased transesterification of EPA into soy phosphatidylcholine. Simultaneously, the recovered glycerolipid products showed decreased hydrolysis of newly synthesized EPA- and DHA-containing glycerolipids.
• ヒト赤血球変形態に及ぼす高度不飽和脂肪酸含有リン脂質処理(in vitro)の影響

  野島 正博, 細川 雅史, 高橋 是太郎, 羽田野 六男, 菊池 佑二

  日本水産学会誌 61 2 197 - 203 日本水産學會 1995年03月 [査読有り][通常論文]
   

  The flow rate of human erythrocytes on microchannels was measured to evaluate their deformability when treated with soy phospholipids, hydrogenated soy phospholipids, phospholipids containing icosape-ntaenoic acid (EPA) and docosahexaenoic acid (DHA). EPA-containing phosphatidylserine and DHA-containing phosphatidylcholine or phosphatidylethanolamine were observed to be the most effective lipid molecular species to improve the deformability of human erythrocytes, while hydrogenated phospho-lipids tended to impair deformability.
• EFFECT OF EPA AND DHA CONTAINING GLYCEROPHOSPHOLIPID MOLECULAR-SPECIES ON THE FLUIDITY OF ERYTHROCYTE CELL-MEMBRANES

  M NOJIMA, M HOSOKAWA, K TAKAHASHI, M HATANO

  FISHERIES SCIENCE 60 6 729 - 734 1994年12月 [査読有り][通常論文]
   

  Fluorescence depolarization of erythrocytes was measured to evaluate the increase in fluidity of cell membrane due to treatment with soy phospholipids, hydrogenated soy phospholipids, icosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) containing phospholipids. When the erythrocytes were treated with EPA or DHA containing phosphatidylethanolamine or phosphatidylserine, the least fluorescence polarization was observed, followed by EPA or DHA containing phosphatidylcholine. All of the hydrogenated phospholipids increased fluorescence depolarization. 2,4,6-Trinitrobenzenesulfonic acid fluorescence quenching proved that the phospholipids used for erythrocytes treatment are incorporated mainly into the inner layer of their cell membrane.
• Phospholipase A2‐mediated synthesis of phosphatidylethanolamine containing highly unsaturated fatty acids

  MASASHI HOSOKAWA, KORETARO TAKAHASHI, MUTSUO HATANO, MAKOTO EGI

  International Journal of Food Science & Technology 29 6 721 - 725 1994年 [査読有り][通常論文]
   

  Phosphatidylethanolamine (PE), which contains highly unsaturated fatty acid (HUFA) specifically in sn‐2 position, was synthesized by porcine pancreatic phospholipase A2‐catalysed esterification of lysophosphatidylethanolamine with HUFA. the use of glycerol containing only a little water as solvent was the important key to this reaction. A 27% yield of up to 94.5%sn‐2 eicosapentaenoic acid (EPA)‐containing PE was obtained using > 99% EPA as a substrate HUFA. Copyright © 1994, Wiley Blackwell. All rights reserved
• ホスホリパ-ゼA2による高度不飽和脂肪酸含有ホスファチジルコリンの合成と細胞分化誘導作用に及ぼす影響

  細川 雅史, 大島 宏哲, 甲野 裕之, 高橋 是太郎, 羽田野 六男, 小田島 粛夫

  日本水産学会誌 59 2 309 - 314 日本水産學會 1993年02月 [査読有り][通常論文]
   

  Phosphatidylcholine containing highly unsaturated fatty acid (HUFA-PC) was prepared by porcine pancreatic phospholipase A2, which catalyzed esterification between lysophosphatidylcholine (LPC) and highly unsaturated fatty acid (HUFA), under a scaled-up reaction system. Fatty acid mixture prepared from sardine oil, purified eicosapentaenoic acid (EPA), and purified docosahexaenoic acid (DHA) were used as the substrates of HUFA. The yield of HUFA-PC was 17.0-19.9%. Synthesized phosphatidylcholine containing DHA (DHA-PC) prepared from LPC and DHA had a DHA content of 46.5%, which indicated alm...
• 工業用ホスホリパ-ゼA2による高度不胞和脂肪酸含有リン脂質の合成

  細川 雅史

  日本食品工業学会誌 38 8 p695 - 698 日本食品工業学会 1991年08月 [査読有り][通常論文]
   

  乳化剤として市販されているリゾ型リン脂質より調製したLPC，ならびにイワシ油をケン化して調製したHUFAを基質として用い，ブタ膵臓由来ホスホリパーゼA2触媒によるHUFA含有PCの合成を行った．合成されたPCの脂肪酸の濃度は，基質として用いた脂肪酸の濃度に影響され，2位の位置に選択的に導入されることが明らかになった．Phospholipids consist of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were synthesized by use of an industrial pancreatic phospholipase A2. Lysophosphatidylcholine (LPC) isolated from a commercial emulsifier, mixed fatty acids obtained from sardine oil, the concentrated sardine oil (EPA+DHA>60%), and 99.4% EPA were used as substrates. Optimum water content was found to 13.4%/system, and optimum ratio of LPC to mixed free...
• リパーゼを用いて合成した高度不飽和脂肪酸含有油脂の分子種

  長田恭一, 高橋是太郎, 羽田野六男, 細川雅史

  日本水産学会誌 57 1 119 - 125 日本水産学会 1991年 [査読有り][通常論文]
   

  Enzymatic glyceride synthesis and acid interchange using icosapentaenoic acid (EPA), docosahexaenoic acid (DHA), γ-linolenic acid (GLA), and EPA and DHA concentrated saponified fatty acid mixture obtained from sardine oil were carried out through the use of four kinds of microbial lipases. Lipase TOYO (Chromobacterium viscosum) was the most effective enzyme for glyceride synthesis as well as acid interchange of triglyceride (TG) rich in polyunsaturated fatty acids. There was a general tendency, except with Lipase TOYO, that DHA was difficult to be incorporated into a glycerol molecule compared to the other fatty acids. Fatty acid composition of TG synthesized from a highly concentrated fatty acid mixture (EPA+DHA: 68.8%) by the use of Lipase TOYO and Lipase OF (Candida cylindracea), directly reflected that of the substrate fatty acid flixture (i.e. EPA+DHA was more than 65%). And the TG molecular species having combination of only EPA and DHA such as (EPA, EPA, EPA), (EPA, EPA, DHA), (EPA, DHA, DHA), and (DHA, DHA, DHA) were dominant accounting for the half of the obtained TG.

MISC

• 北太平洋に分布する動物プランクトン群集の脂質特性分析

  笹川拓真, 山口篤, 高谷直己, 細川雅史, 別府史章 日本水産学会大会講演要旨集(CD-ROM) 2024 2024年
• 海洋細菌が産生する希少カロテノイドの同定と抗炎症活性評価

  高谷直己, 別府史章, 細川雅史 日本水産学会大会講演要旨集(CD-ROM) 2024 2024年
• 函館沿岸で採取したキングサーモンの脂質特性

  李旻軒, 横山楓, 滑げい卓, 高谷直己, 別府史章, 細川雅史 日本水産学会北海道支部大会講演要旨集 2023 (CD-ROM) 2024年
• バキュロウィルスを用いた褐藻カロテノイド生合成関連酵素の機能実証

  井上晶, 高谷直己, 細川雅史, 尾島孝男 マリンバイオテクノロジー学会大会講演要旨集 23rd 2023年
• 海洋性カロテノイドastaxanthinの生体内代謝物の同定と組織分布

  高谷直己, 向村奏, 別府史章, 細川雅史 日本水産学会大会講演要旨集(CD-ROM) 2023 2023年
• n-3PUFA結合ホスファチジルグリセロールの細胞内脂肪酸調節機構の解明

  富樫咲, 別府史章, 高谷直己, 細川雅史 日本水産学会大会講演要旨集(CD-ROM) 2023 2023年
• 昆虫細胞を用いた褐藻類β-カロテン水酸化酵素の同定

  井上晶, 高谷直己, 細川雅史, 尾島孝男 日本水産学会大会講演要旨集(CD-ROM) 2022 2022年
• イトマキヒトデ脂質成分によるC2C12細胞の筋管形成促進効果

  別府史章, 福島葵, 高谷直己, 細川雅史 日本水産学会大会講演要旨集(CD-ROM) 2022 2022年
• 水産物由来アルキルグリセロールによるC2C12筋管サイズ増大効果

  佐々木健朗, 亀山美宇, 高谷直己, 細川雅史, 別府史章 日本栄養・食糧学会大会講演要旨集 76th 2022年
• 海洋性カロテノイドfucoxanthinの新規生体内代謝物の同定と組織分布解析

  高谷直己, 向村奏, 永田航大, 田谷大輔, 別府史章, 細川雅史 日本栄養・食糧学会大会講演要旨集 76th 2022年
• 糖尿病肥満モデルKK-A^yマウスにおける水産物由来モノアルキル型中性脂質の脂質代謝への影響

  柿本真幸, 高谷直己, 細川雅史, 別府史章 日本水産学会大会講演要旨集(CD-ROM) 2022 2022年
• ドスイカ(Berryteuthis magister)由来モノアルキル型中性脂質の2型糖尿病モデルKK-A^yマウスに対する脂質代謝への影響評価

  柿本真幸, 高谷直己, 細川雅史, 別府史章 日本水産学会大会講演要旨集(CD-ROM) 2021 2021年
• フコキサンチン生体内代謝物の合成および構造解析

  向村奏, 永田航大, 高谷直己, 別府史章, 細川雅史 日本農芸化学会北海道支部学術講演会講演要旨集(Web) 2021 2021年
• 高度不飽和ホスファチジルグリセロールの酵素的合成と肝臓脂質低下作用

  陳莉萍, 高谷直己, 別府文章, 宮下和夫, 細川雅史 日本水産学会大会講演要旨集 2020 2020年
• 非アルコール性脂肪肝炎誘導モデルマウスに対する海洋性カロテノイドfucoxanthinの炎症抑制作用

  高谷直己, 河野友香, 別府史章, 宮下和夫, 細川雅史 日本栄養・食糧学会大会講演要旨集 74th 2020年
• フコキサンチンによる非アルコール性脂肪肝炎抑制効果 (特集 脂質がつなぐもの : 生物工学的脂質研究が導く新しい学際研究と産業(後編))

  高谷 直己, 細川 雅史 生物工学会誌 98 (10) 529 -532 2020年
• Furan fatty acidss-a new approach

  Matt Miller, Donato Romanazzi, Masashi Hosokawa, Hajime Uchida INFORM 30 25 -27 2019年03月01日 [査読無し][通常論文]
   

  © 2019, American Oil Chemists' Society. All rights reserved. Furan fatty acids (F-acids) are minor lipid components in organisms, plants, and mammals. F-acids have a number of different species according to chain length on the alpha-positions of the furan ring and methylation of the ring, as outlined in Figure 1. F-acids have been identified in a number of fish species, particularly in the liver and gonads. The concentration of F-acids in liver oil from Northern pike can be as high as 5%, but the F-acids in oil from the pike’s testes can be as high as 65%.
• n-3高度不飽和脂肪酸によるC2C12細胞の筋分化能保護効果

  別府史章, 山崎凌平, 宮下和夫, 細川雅史 日本栄養・食糧学会大会講演要旨集 73rd 2019年
• C2C12筋芽細胞におけるEPA/DHAの筋管形成能保護効果

  別府史章, 山崎凌平, 宮下和夫, 細川雅史 日本油化学会年会講演要旨集 58th 2019年
• ジヒドロキシ脂肪酸による糖尿病/肥満マウスの糖・脂質代謝改善作用

  藤翔太, 別府史章, KIM Hak-Ryul, HOU Ching T., 宮下和夫, 細川雅史 日本油化学会年会講演要旨集 58th 2019年
• アカモクからのMCT抽出油の機能性評価

  松本卓己, 手良向一嘉, 別府史章, 細川雅史, 宮下和夫 日本油化学会年会講演要旨集 58th 2019年
• フコキサンチンのUCP1欠損マウスにおけるミトコンドリア因子の発現誘導

  秋田知輝, 岡松優子, 別府史章, 宮下和夫, 細川雅史 日本油化学会年会講演要旨集 58th 2019年
• 海洋性カロテノイドfucoxanthinの新規生体内開裂物による炎症抑制機構

  高谷直己, 田谷大輔, 宮下和夫, 細川雅史 日本栄養・食糧学会大会講演要旨集 73rd 2019年
• アスタキサンチン由来アポカロテノイドによる炎症抑制機構

  高谷直己, 別府史章, 宮下和夫, 細川雅史 日本油化学会年会講演要旨集 58th 2019年
• 食品中のカロテノイド類

  小泉次郎, 細川雅史 農業および園芸 92 (10) 875‐880 -880 2017年10月01日 [査読無し][通常論文]
  
• Fucoxanthin in the management of obesity and its related disorders

  Kazuo Miyashita, Masashi Hosokawa JOURNAL OF FUNCTIONAL FOODS 36 195 -202 2017年09月 [査読無し][通常論文]
   

  Interest in a novel biological agent fucoxanthin (Fx) has been growing in recent years, which connects Fx to increases in energy expenditure and has implications for the management of obesity and type 2 diabetes mellitus (T2DM). Several molecular targets offer the most hope for influencing energy expenditure. One of the keys for success will be uncoupling protein 1 (UCP1). Fx can reduce the excess fat accumulation in abdominal white adipose tissue (WAT), which is primarily based on the up-regulation of the thermogenesis through UCP1 expression in both brown adipose tissue (BAT) and abdominal WAT. Fx down regulates the expression of pro-inflammatory adipokines involved in insulin resistance from abdominal WAT and subsequently normalizes the blood glucose level. In addition, Fx can promote glucose utilization in skeletal muscle by up-regulating glucose transporter 4 (GLUT4) expression and promoting its translocation to the cell membrane from the cytosol. (C) 2017 Elsevier Ltd. All rights reserved.
• 水産脂質成分の特徴と機能性 (特集 機能性脂質研究の最前線と市場展開)

  細川 雅史 Food style 21 21 (6) 39 -44 2017年06月 [査読無し][通常論文]
  
• 食品因子による生活習慣病予防・改善機構の解明をめざして―3 褐藻由来フコキサンチンの抗肥満・抗糖尿病効果とその機序

  西川翔, 細川雅史, 宮下和夫 化学と生物 54 (8) 580‐585 -585 2016年07月20日 [査読無し][通常論文]
  
• 海洋性カロテノイドの健康機能

  細川 雅史 ニューフードインダストリー 58 (6) 7 -12 2016年06月 [査読無し][通常論文]
  
• Biological importance of fucoxanthin and its metabolites

  Kazuo Miyashita, Masashi Hosokawa, Nana Mikami, Yasuo Kokai ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY 250 2015年08月 [査読有り][通常論文]
  
• 海洋細菌Jejuia pallidilutea 11shimoA1株の新規カロテノイド生合成系解析

  高谷直己, 澤辺智雄, 宮下和夫, 細川雅史 マリンバイオテクノロジー学会大会講演要旨集 17th 2015年
• 新規な生体親和性化粧品素材ホスファチジル-パンテノールの抗炎症作用と分子機構の解明

  細川 雅史 コスメトロジー研究報告 23 111 -116 2015年 [査読無し][通常論文]
  
• ニュートリゲノミクス解析に基づく褐藻カロテノイド,フコキサンチンの栄養機能性 (特集 ニュートリゲノミクス : 学問分野としての成熟とこれから) -- (現在のニュートリゲノミクス研究)

  宮下 和夫, 細川 雅史 遺伝 : 生物の科学 69 (1) 21 -27 2015年01月 [査読無し][通常論文]
  
• 海洋細菌が有するカロテノイド合成系の体系的理解:フラボバクテリアにおけるmyxol合成系の特徴

  中西誠人, 高谷直己, 高峰, 宮下和夫, 細川雅史, 大熊盛也, 大島健志朗, 服部正平, 澤辺智雄 日本水産学会大会講演要旨集 2014 34 2014年09月19日 [査読無し][通常論文]
  
• PPARγを活性化させる新規ニシン発酵食品の脂質解析

  濱岡直裕, 中川良二, 太田智樹, 長島浩二, 細川雅史, 宮下和夫 日本油化学会年会講演要旨集 53rd 86 2014年09月09日 [査読無し][通常論文]
  
• マリンカロテノイドの炎症性疾患予防作用

  細川 雅史 微量栄養素研究 31 80 -87 2014年 [査読無し][通常論文]
  
• 褐藻カロテノイド,フコキサンチンのUCP1発現亢進作用 (特集 褐色脂肪細胞と食品成分 : 抗肥満へのアプローチ)

  宮下 和夫, 細川 雅史 Bio industry 30 (11) 31 -38 2013年11月 [査読無し][通常論文]
  
• 第二回日韓水産学会合同シンポジュウムに参加して

  細川 雅史 日本水産學會誌 = Bulletin of the Japanese Society of Scientific Fisheries 79 (4) 744 -745 2013年07月15日 [査読無し][通常論文]
  
• 海洋細菌Jejuia pallidilutea A1株の新規カロテノイド合成とストレス応答

  高谷直己, 西田健太郎, 澤辺智雄, 宮下和夫, 細川雅史 マリンバイオテクノロジー学会大会講演要旨集 15th 2013年
• クロレラに含まれるカロテノイドの定量とケン化反応による濃縮

  加茂川 寛之, 細川 雅史, 阿部 真幸, 宮下 和夫 北海道大学水産科学研究彙報 62 (3) 83 -88 2012年12月14日 [査読無し][通常論文]
   

  Carotenoids are natural pigments found in plants, seaweeds, algae and bacteria. It is well know that carotenoids have physiological effects such as provitamin activity and antioxidative effect. Among carotenoids, -carotene, lutein and zeaxanthin are popular carotenoids in green leafy vegetables and green microalgae. Furthermore, violaxanthin and neoxanthin are also contained as minor carotenoids. These carotenoids are currently expected to exhibit health beneficial effects depend on their unique structure. However, there are only a few reports of quantitative analysis of neoxanthin and vio...
• 脂肪を燃やす二つの脂肪組織(バイオミディア)

  細川 雅史 生物工学会誌 : seibutsu-kogaku kaishi 90 (11) 740 -740 2012年11月25日 [査読無し][通常論文]
  
• 脂肪を燃やす二つの脂肪組織

  細川雅史 生物工学会誌 90 (11) 740 -740 2012年11月25日 [査読無し][通常論文]
  
• フコキサンチンの抗肥満作用とその分子機構

  細川 雅史 日本水産學會誌 = Bulletin of the Japanese Society of Scientific Fisheries 78 (5) 1007 -1007 2012年09月15日 [査読無し][通常論文]
  
• ヘマトコッカス藻由来アスタキサンチンの潰瘍性大腸炎予防効果

  木澤有希, 山下栄次, 宮下和夫, 細川雅史 日本水産学会大会講演要旨集 2012 74 2012年09月14日 [査読無し][通常論文]
  
• 高度不飽和脂肪酸含有糖脂質の酸化安定性に関する研究

  山口智代, 細川雅史, 阿部真幸, 宮下和夫 日本水産学会大会講演要旨集 2012 111 2012年03月26日 [査読無し][通常論文]
  
• 褐藻脂質の多機能性と食品への活用 (特集 機能性食品探索のフロンティア)

  宮下 和夫, 細川 雅史 Bio industry 29 (2) 7 -14 2012年02月 [査読無し][通常論文]
  
• 褐藻由来フコキサンチンの白色脂肪組織におけるUCP1発現誘導機構

  小出愛, 松本伊代, 別府史章, 前多隼人, 細川雅史, 宮下和夫 日本農芸化学会大会講演要旨集(Web) 2012 2012年
• I-5. フコキサンチンの抗肥満作用とその分子機構

  細川 雅史 日本水産学会誌 78 (5) 1007 -1007 2012年 [査読無し][通常論文]
  
• ホスホリパーゼを用いた機能性化合物のリン脂質誘導化法に関する研究 (新任者の論文)

  山本 幸弘, 細川 雅史, 宮下 和夫 成蹊大学理工学研究報告 48 (2) 59 -62 2011年12月 [査読無し][通常論文]
   

  Here I describe about the phosphatidylation of functional compounds using phospholipases which is covered with my doctoral thesis. Physiologically active compound such as conjugated fatty acid, terpenes and phenolic compounds sometime exert their activity not fully because of their poor solubility in a certain environment. On the other hand, phospholipids have characteristic amphiphilic property and biocompatibility. In this study, several physiologically active compounds were phosphatidylated using phospholipases such as phospholipase A2 and phospholipase D. The enzymatic reaction was modi...
• 褐藻類に含まれる機能性n‐3系PUFAの酸化安定性

  須田正剛, 阿部真幸, 細川雅史, 宮下和夫 日本水産学会大会講演要旨集 2011 104 2011年09月28日 [査読無し][通常論文]
  
• 褐藻脂質中のフコキサンチン含有と脂肪酸組成の季節変動

  植西洋平, 野村雅俊, 阿部真幸, 細川雅史, 宮下和夫, 安井肇 日本水産学会大会講演要旨集 2011 104 2011年09月28日 [査読無し][通常論文]
  
• 渇藻カロテノイド,フコキサンチンの生体内抗酸化活性

  AIRANTHI Widjaja‐Adhi, 岩崎さやか, 山口智代, 阿部真幸, 阿部真幸, 細川雅史, 宮下和夫 日本食品科学工学会大会講演集 58th 91 2011年09月09日 [査読無し][通常論文]
  
• マリンケミカル"フコキサンチン"の抗肥満・抗糖尿病作用 (特集 進化と深化をはじめた機能性食品の世界(2)地方の独自性がもたらす多彩な科学技術)

  細川 雅史 マテリアルインテグレ-ション 24 (8) 6 -10 2011年08月 [査読無し][通常論文]
  
• Preface

  Ernesto M. Hernandez, Masashi Hosokawa Omega-3 Oils: Applications in Functional Foods v 2011年05月01日 [査読無し][通常論文]
  
• Omega-3 Oils: Applications in Functional Foods

  Ernesto M. Hernandez, Masashi Hosokawa Omega-3 Oils: Applications in Functional Foods 1 -305 2011年05月01日 [査読無し][通常論文]
   

  This book addresses new applications of omega-3 fatty acids from both plant and marine sources in food supplements and pharmaceuticals and covers three basic areas: structure and function, production and processing, and health effects. The authors review the latest clinical evidence on the impact of consumption of omega-3 polyunsaturated fatty acids on prevalent human diseases such as inflammation-related illnesses in general and cardiovascular illnesses in particular. They also examine technologies to purify marine oils and protect them against oxidation as well as novel techniques for their incorporation into foods.
• Synergistic/Additive Health Effects of Fish Oil and Bio-Active Compounds

  Tomoko Okada, Nana Mikami, Tomoyuki Okumura, Masashi Hosokawa, Kazuo Miyashita Omega-3 Oils: Applications in Functional Foods 177 -203 2011年05月01日 [査読無し][通常論文]
   

  This chapter describes the current body of knowledge regarding the additive effects of fish oil and bio-active agents on the prevention and remediation of clinical disorders. It discusses the singular effect of fish oil consumption in relation to a specific illness, followed by the reported synergistic/additive effects of fish oil combined with bio-active agents. There is substantial evidence that fish oil possesses various physiological activity benefits in human health. The chapter discusses concomitant applications of fish oil with bio-active compounds for the remediation of a variety of clinical disorders. By combinative therapy, the well-documented beneficial health effect of fish oil can possibly be maximized in various approaches. Although this area of research is still in its early stages, it has been receiving increasing attention with the realization that combinative application of fish oil and bio-active compounds may provide vital outcomes and facilitate progress toward the design of beneficial clinical therapies for human health. Studies aimed at finding superior combinative effects of fish oil and bio-active compounds, along with their mechanisms of action, may eventually lead to reductions in the mortality and morbidity rates associated with human health disorders and complications that are of growing concern in modern society.
• 2-I-29 フコキサンチンと活性型ビタミンD_3による複合的大腸がん細胞増殖抑制の作用解析(一般演題要旨,日本ビタミン学会第63回大会講演要旨)

  寺崎 将, 長尾 昭彦, 田中 卓二, 細川 雅史, 宮下 和夫, 増田 園子 ビタミン 85 (4) 250 -250 2011年04月25日
• 褐藻由来フコキサンチンによる肝臓でのSCD1発現抑制作用

  別府史章, 篠田太郎, 細川雅史, 宮下和夫 日本水産学会大会講演要旨集 2011 2011年
• フコキサンチンによる白色脂肪組織の肥大化抑制機構

  細川雅史, 任美珍, 小出愛, 西川翔, 別府史章, 宮下和夫 肥満研究 17 (Supplement) 2011年
• フコキサンチンの肥満初期における予防効果と抗炎症作用

  任美珍, 別府史章, 宮下和夫, 細川雅史 日本農芸化学会大会講演要旨集 2011 2011年
• ホタテ卵巣を用いた新規発酵食品の製造と脂質の酸化安定性に関する検討

  濱岡直裕, 濱岡直裕, 太田智樹, 細川雅史, 宮下和夫 日本食品科学工学会大会講演集 58th 2011年
• カロテノイド(8)フコキサンチン

  細川 雅史 Functional food 5 (1) 94 -98 2011年 [査読無し][通常論文]
  
• 2-I-16 活性型ビタミンD_3,Fucoxanthin,Shikoninによる複合的大腸がん細胞増殖抑制作用(一般演題,日本ビタミン学会第62回大会発表要旨)

  寺崎 将, 高上馬 希重, 関崎 春雄, 長尾 明彦, 田中 卓二, 細川 雅史, 宮下 和夫, 増田 園子 ビタミン 84 (4) 174 -174 2010年04月25日
• HepG2におけるα-リノレン酸の代謝

  津久井隆行, 細川雅史, 宮下和夫 日本農芸化学会大会講演要旨集 2010 2010年
• フコキサンチンによるマクロファージおよびCD8+T細胞の白色脂肪組織への浸潤抑制作用

  細川雅史, 任美珍, 別府史章, 宮下和夫 肥満研究 16 (Supplement) 2010年
• アロニアエタノール抽出物の脂質代謝改善効果

  梨田幸恵, 三上奈々, 細川雅史, 太田智樹, 宮下和夫 日本食品科学工学会大会講演集 57th 2010年
• これからの脂質栄養と機能性食品の開発--海藻の恵みとその利用

  宮下 和夫, 細川 雅史 脂質栄養学 19 (1) 39 -45 2010年 [査読無し][通常論文]
  
• アスタキサンチンのデキストラン硫酸ナトリウム誘発マウス大腸炎に対する予防効果

  細川 雅史, 安井 由美子, 三瓶 雄司, 三上 奈々, 宮下 和夫, 田中 卓二 日本栄養・食糧学会大会講演要旨集 63回 192 -192 2009年05月 [査読無し][通常論文]
  
• 海洋生命統御による食糧生産--北海道大学21世紀COEプログラム(4)新たな水産資源としての海藻の重要性

  宮下 和夫, 細川 雅史 アクアネット 11 (12) 78 -82 2008年12月 [査読無し][通常論文]
  
• AGFD 62-The suppression effects of conjugated linolenic acids on chemically induced colon carcinogenesis.

  Yumiko Yasui, Masashi Hosokawa, Kazuo Miyashita, Takuji Tanaka ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY 236 2008年08月 [査読無し][通常論文]
  
• フコキサンチンの安全性評価

  別府史章, 倉智麻木, 庭野吉己, 津久井隆行, 前多隼人, 細川雅史, 宮下和夫 日本栄養・食糧学会大会講演要旨集 62nd 2008年
• 内臓脂肪蓄積と食品機能成分:特にフコキサンチンについて (肥満と機能性食品)

  前多 隼人, 細川 雅史, 宮下 和夫 Functional food 1 (2) 159 -165 2008年 [査読無し][通常論文]
  
• 褐藻由来フコキサンチンのDHA増加作用

  津久井隆行, 細川雅史, 宮下和夫 生化学 2007年
• ワカメ由来フコキサンチンの正常マウスに対する肝臓中のDHA増加効果

  津久井隆行, 細川雅史, 宮下和夫 日本油化学会年会講演要旨集 46th 2007年
• Chemopreventive effects of conjugated linolenic acids (CLN) occurring in plant seed oils

  Bhaskar Narayan, Masashi Hosokawa, Yumiko Yasui, Rikako Suzuki, Hiroyuki Kohno, Takuji Tanaka, Kazuo Miyashita Current Nutrition and Food Science 3 (4) 309 -318 2007年 [査読無し][通常論文]
   

  Conjugated fatty acids (CFA) being novel type of biologically functional lipid substances, have received increased interest owing to their beneficial effects on human health. Among CFAs, conjugated linoleic acids (CLA) have been reviewed extensively for their occurrence, health benefits, industrial production and applications. On the contrary, it is worth noting that some plant seeds contain conjugated linolenic acids (CLN) at considerably higher levels (30 to 70 wt% lipid), although other kinds of CFAs including CLA are only found at concentrations less than 1% in natural products. It is thus imperative that CLN are the only CFAs that occur in higher quantities in nature and we have extensively screened CLN from different plant seed oils for their chemopreventive effects. In the ensuing review, we describe in detail the physiological functions of CLN isomers that occur in some plant seeds. CLN from natural origin showed growth inhibitory and apoptotic effects on cancer cells and the activity was dependent on their geometrical/positional structures. All trans CLN exerted stronger growth inhibition and more DNA fragmentation in human colon cancer cells than corresponding CLN isomer with cis configuration. CLN induced apoptosis through decrease of Bcl-2 protein. It will be interacted with increase in PPARγ signaling and up-regulation of gene expression of GADD45 and p53. Enhancement of PPARγ expression was also observed in the rats fed seed oil rich in CLN. Dietary feeding of these CLN-containing seed oil reduced the frequency of colonic aberrant crypt foci (ACF) in rat that is the precursor of colon carcinogenesis in short-term experiment and inhibited the development of colonic adenocarcinoma in long-term experiment. © 2007 Bentham Science Publishers Ltd.
• 水産脂溶性成分の機能性評価と高度利用に関する研究

  細川 雅史 Oleoscience 7 (12) 525 -532 2007年 [査読無し][通常論文]
   

  水産物中に含まれる脂溶性成分の有効利用を目指し, それらの機能性評価や高機能化に関して研究を行った。ワカメなどの食用海藻中に含まれるフコキサンチンは, ヒト白血病細胞や大腸癌細胞に対してアポトーシスを誘導した。このようなアポトーシス誘導能は, ホヤから分離したフコキサンチンの類縁カロテノイドであるフコキサンチノールやハロシンチアキサンチンでより顕著であることを見い出した。また, フコキサンチンは, 糖尿病/肥満マウスの内臓脂肪の蓄積や高血糖を改善する作用を示した。一方, 優れた生理機能を有し幅広い利用が期待できる高度不飽和リン脂質の調製には, 酵素的合成反応が有効であった。とくに, 必須水分代替物の利用により反応収率が顕著に上昇することを示した。また, 高度不飽和脂肪酸から新規な機能性が期待される環状ヒドロキシ脂肪酸を調製するには生物変換反応が有効であった。
• 第41回日本油化学会進歩賞 水産脂溶性成分の機能性評価と高度利用に関する研究

  細川 雅史 オレオサイエンス 7 (12) 525 -532 2007年 [査読無し][通常論文]
  
• Fucoxanthin, from edible seaweeds, and its multi-biological functions

  Kazuo Miyashita, Masashi Hosokawa, Tokutake Sashima ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY 232 279 -279 2006年09月 [査読無し][通常論文]
  
• Physiological effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) - A review

  B Narayan, K Miyashita, M Hosokawa FOOD REVIEWS INTERNATIONAL 22 (3) 291 -307 2006年07月 [査読無し][通常論文]
   

  Marine lipids have long been documented to be the major source of polyunsaturated fatty acids (PUFAs), especially n-3 fatty acids such as eicosapentaenoic acid (EPA; 20:5 n-3) and docosahexaenoic acid (DHA; 22:6 n-3). Both EPA and DHA have been documented to have significant influence on biochemical and physiological changes in the body. Although these long chain PUFA exert positive influences on human nutrition and health, there are also some controversies pertaining to the functioning of these n-3 PUFAs including the extent of their requirement by the body. As marine lipids have been thoroughly reviewed often, the present review mainly focuses on works related to physiological effects of EPA and DHA.
• 北海道支部の活性化 : 支部大会での新たな試み(支部のページ)

  細川 雅史, 澤谷 拓治, 山崎 浩司, 武田 浩郁, 天野 春菜 日本水産学会誌 71 (3) 385 -387 2005年05月15日 [査読無し][通常論文]
  
• 海藻由来フコキサンチンの脂肪細胞に対する分化調節機能と抗肥満効果 (特集:フィトケミカルの機能性(2))

  前多 隼人, 細川 雅史, 宮下 和夫 食品工業 48 (8) 68 -74 2005年04月30日 [査読無し][通常論文]
  
• 海藻脂質の知られざる健康機能 : 褐藻フコキサンチンに脂肪蓄積抑制などの機能

  細川 雅史, 宮下 和夫 化学と生物 43 (3) 150 -152 2005年03月01日 [査読無し][通常論文]
  
• 9 trans,11 trans型CLAのヒト結腸ガン細胞に対する

  別府史章, 細川雅史, 田中礼央, 宮下和夫 日本農芸化学会大会講演要旨集 2005 2005年
• 「がん予防食品開発の新展開 －予防医学におけるバイオマーカーの評価システム－」<大澤俊彦編>

  シーエムシー出版 2005年 [査読無し][通常論文]
  
• Yasui, Y., Hosokawa, M., Kohno, H., Tanaka, T. and Miyashita, K.:" Chemopreventive effect of bitter gpourd seed oil rich in conjugated linolenic acid", Chapter 3, 30-41 (Hung, Y.S., Yanagita, T. and Knapp, H.R., AOCS Press, Champain, IL, USA)(2005)

  2005年 [査読無し][通常論文]
  
• Hosokawa, M. and Takahashi, K.:"Preparation of polyunsaturated phospholipids and their functional properties", Chapter 13, 13.1-13.13 (Hou, C.T.:"Handbook of Industrial Biocatalysis", CRC Press Taylor & Francis, Boca Raton, FL, USA)(2005)

  2005年 [査読無し][通常論文]
  
• 「油脂・脂質の基礎と応用－栄養・健康から工業まで－」<日本油化学会編>

  日本油化学会 2005年 [査読無し][通常論文]
  
• Takahashi, K. and Hosokawa, M.:"Functionalities and production with biocatalysis of two highly polyunsaturated phospholipids", Chapter 19, 274-284(Hung, Y.S., Yanagita, T. and Knapp, H.R., AOCS Press, Champain, IL, USA)(2005)

  2005年 [査読無し][通常論文]
  
• BIO R&D がん細胞を自滅させる海藻カロテノイド--フコキサンチンによるアポトーシス誘導

  細川 雅史 バイオインダストリー 21 (1) 52 -57 2004年01月 [査読無し][通常論文]
  
• 油化学辞典

  丸善 2004年 [査読無し][通常論文]
  
• 『水産食品栄養学-基礎からヒトへ-』<鈴木平光編>

  技報堂 2004年 [査読無し][通常論文]
  
• ファインケミカルシリーズ『機能性脂質のフロンティア』<佐藤清隆・柳田晃良・和田俊 編>

  シーエムシー出版 2004年 [査読無し][通常論文]
  
• 水産学シリーズ142『水産機能性脂質』<高橋是太郎>

  恒星社厚生閣 2004年 [査読無し][通常論文]
  
• サモアーゼRによる遡上シロサケ筋肉のアンジオテンシンI変換酵素阻害ベプチドへの変換反応の設定

  小野 聖吾, 細川 雅史, 宮下 和夫, 高橋 是太郎 北海道大学水産科学研究彙報 54 (1) 1 -5 2003年07月 [査読無し][通常論文]
  
• ニガウリ種子油(BGO)によるazoxymethane(AOM)誘発ラット大腸発がん抑制

  鈴木里加子, 甲野裕之, 山口かずえ, 細川雅史, 宮下和夫, 田中卓二 日本癌学会総会記事 62nd 2003年
• Fujimoto, A., Sassaki, J., Hosokawa, M. and Takahashi, K.:"Fibrosarcoma may be suppressed by liposomal sn-2 DHA inserted phospolipid therapy", In Essential Fatty Acids and Eicosanoids Invited Paper from the Fifth International Congress, AOCS Press, Cha・・・

  2003年 [査読無し][通常論文]
   

  Fujimoto, A., Sassaki, J., Hosokawa, M. and Takahashi, K.:"Fibrosarcoma may be suppressed by liposomal sn-2 DHA inserted phospolipid therapy", In Essential Fatty Acids and Eicosanoids Invited Paper from the Fifth International Congress, AOCS Press, Champain (Y.S. Hung, S.J. Lin, P.C. Hung ed), (2003)pp. 290-295.
• Hou, C.T., Hosokawa, M. and Iwasaki, Y.:"Bioconversion of unsaturated fatty acids to value-added functional products", In Essential Fatty Acids and Eicosanoids Invited Paper from the Fifth International Congress, AOCS Press, Champain (Y.S. Hung, S.J. L・・・

  2003年 [査読無し][通常論文]
   

  Hou, C.T., Hosokawa, M. and Iwasaki, Y.:"Bioconversion of unsaturated fatty acids to value-added functional products", In Essential Fatty Acids and Eicosanoids Invited Paper from the Fifth International Congress, AOCS Press, Champain (Y.S. Hung, S.J. Lin, P.C. Hung ed), (2003)pp. 12-17.
• Hosokawa, M., Hou, C.T., Weisleder, D. and Brown, W."Formation of cyclic products from polyunsaturated fatty acids by Clavibacter sp. ALA2", In Essential Fatty Acids and Eicosanoids Invited Paper from the Fifth International Congress, AOCS Press, Champ・・・

  2003年 [査読無し][通常論文]
   

  Hosokawa, M., Hou, C.T., Weisleder, D. and Brown, W."Formation of cyclic products from polyunsaturated fatty acids by Clavibacter sp. ALA2", In Essential Fatty Acids and Eicosanoids Invited Paper from the Fifth International Congress, AOCS Press, Champain (Y.S. Hung, S.J. Lin, P.C. Hung ed), (2003)pp. 36-41.
• Noguchi, R., Yasui, Y., Hosokawa, M., Fukunaga, K. and Miyashita, K.:"Bioconversion of CLN to CLA", In Essential Fatty Acids and Eicosanoids Invited Paper from the Fifth International Congress, AOCS Press, Champain (Y.S. Hung, S.J. Lin, P.C. Hung ed), ・・・

  2003年 [査読無し][通常論文]
   

  Noguchi, R., Yasui, Y., Hosokawa, M., Fukunaga, K. and Miyashita, K.:"Bioconversion of CLN to CLA", In Essential Fatty Acids and Eicosanoids Invited Paper from the Fifth International Congress, AOCS Press, Champain (Y.S. Hung, S.J. Lin, P.C. Hung ed), (2003)pp. 353-359.
• 高度不飽和リン脂質の分子構築と生理機能に関する研究(平成13年度日本水産学会賞奨励賞受賞)

  細川 雅史 日本水産学会誌 68 (4) 509 -512 2002年07月 [査読無し][通常論文]
  
• 平成13年度日本水産学会賞奨励賞受賞者(高度不飽和リン脂質の分子構築と生理機能に関する研究)

  細川 雅史 日本水産学会誌 68 (3) 297 -297 2002年05月15日 [査読無し][通常論文]
  
• 高度不飽和リン脂質の酵素的改変と機能特性

  細川 雅史, 高橋 是太郎 オレオサイエンス = / Japan oil chemists' society 2 (1) 19 -25 2002年01月01日 [査読無し][通常論文]
   

  Biocatalytic approaches were rational ways to prepare and modify highly unsaturated phospholipids (HUFA-PL). The prepared HUFA-PL showed an antitumor effect in vivo, a promotional effect on cell differentiation, and an increase in deformability of erythrocytes in vitro.
• 高度不飽和リン脂質リポソームの性状とその抗腫瘍効果

  藤本 章人, 佐々木 甚一, 細川 雅史, 高橋 是太郎 脂質生化学研究 43 (0) 318 -321 2001年05月10日 [査読無し][通常論文]
   

  高度不飽和リン脂質は多様な機能を有する生体適合性(生体親和性)に優れた脂質形態である。本研究では高度不飽和リン脂質リポソームの免疫賦活促進機能を調べることを目的として、フィトグリコーゲン(PG)を内包させた高度不飽和リン脂質リポソーム及びPG未内包高度不飽和リン脂質リポソームを調製し、それらの性状と in vitro, in vivo 相方における抗腫瘍効果について検討した。調製したsn-2位DHA結合型リン脂質リポソーム(PC:PS=7:3 モル比)は6～9層からなるマルチラメラベシクル(MLV)であり、粒度分布のピークは約1 μ m付近にあった。PGを内包させなかったsn-2位DHA結合型リン脂質MLVは少なくとも1ヶ月以上の粒度分布安定性を示し、Meth-A fibrosarcomaに対して比較的強い抗腫瘍効果を示した。
• 植物種子油由来の共役型リノレン酸の細胞に対する致死作用

  野口亮子, 鈴木里加子, 細川雅史, 宮下和夫, 阿部真幸 日本農芸化学会誌 75 2001年
• 第4版油化学便覧<油化学便覧編集委員会>

  丸善 2001年 [査読無し][通常論文]
  
• Takahashi, K. and Hosokawa, M.: “Chapter 25 Production of tailor-made polyunsaturated phospholipids through bioconversions”, 517-526 (Kuo, T.M., Gardner, H.W.: "Lipid Biotechnology", MARCEL DEKKER, INC., New York) (2001)

  2001年 [査読無し][通常論文]
  
• DHA含有リン脂質の酵素変換と生理作用 (「リン脂質の生理作用」)

  高橋 是太郎, 細川 雅史 脂質栄養学 9 (1) 19 -31 2000年 [査読無し][通常論文]
  
• β-リゾ型高度不飽和リン脂質の調製及びヒト赤血球変形能改善効果

  小野 雅代, 細川 雅史, 高橋 是太郎, 井上 良計 脂質生化学研究 40 (0) 204 -206 1998年07月02日 [査読無し][通常論文]
   

  Rhizomucor miehei 由来の固定化リパーゼ剤（リポザイムIM）の水分活性を中間水分活性域に制御することによってDHA強化鶏卵黄リン脂質を部分加水分解し、DHA含量が極めて高いβ-リゾ型リン脂質が得られた。このβ-リゾ型リン脂質は低濃度で速やかに赤血球に取り込まれ、赤血球の変形能を改善した。
• β－リゾ型高度不飽和リン脂質のヒト赤血球変形能改善効果

  小野 雅代, 細川 雅史, 高橋 是太郎, 井上 良計 ヘモレオロジー研究会誌 1 (0) 7 -11 1998年 [査読無し][通常論文]
   

  高度不飽和リン脂質には多彩な生理活性のあることが示唆され始めている。高度不飽和リン脂質は水産物に比較的豊富に含まれてはいるが，水産物より着臭や着色なしに抽出することは一般に難しい。一方，ドコサヘキサエン酸(DHA)を強化した鶏卵黄リン脂質は，着臭や着色が殆どないという利点を有しているが，水産物由来のリン脂質よりもDHA含量が低いという難点があった。我々はこのような点を解決するため，リパーゼによる鶏卵黄リン脂質の部分加水分解反応を試み，DHAを高濃度に含むリン脂質の調製法を確立した。本研究では，このように調製したβーリゾ型高度不飽和リン脂質の生理機能を検討するため，ヒト赤血球変形能改善効果について人工毛細血管モデル(MC-FAN)を用いて評価した。Immobilized lipase (Lipozyme IM) mediated selective partial hydrolysis of docosahexaenoic acid (DHA) enriched egg yolk phospholipids (PL) were carried out. By keeping the water activity of lipase at an intermediate level， DHA was effectively enriched in acyl moieties of...
• リポザイムIMを用いた加水分解反応によるドコサヘキサエン酸結合型リン脂質の濃縮

  小野 雅代, 細川 昌史, 井上 良計, 高橋 是太郎 日本油化学会誌 46 (8) 867 -872,936 1997年 [査読無し][通常論文]
   

  ドコサヘキサエン酸 (DHA) 結合型リン脂質を濃縮するため, Rhizomucor miehei由来のリパーゼを固定化した酵素 (Lipozyme IM) を用いて, n-ヘキサン溶液中でのグリセロリン脂質の選択的部分加水分解反応について検討を行った。DHA強化卵黄レシチンおよび, イカ皮より抽出したレシチンを部分加水分解することにより, リン脂質画分中にDHAのさらなる濃縮がみられた。特に, DHAは他の脂肪酸に比べ加水分解を受けにくいため, リン脂質画分中に最も選択的に濃縮された。Lipozyme IMの水分活性 (a_w) を0.44に調節した場合においてDHAの濃縮が最も顕著であり, DHA強化卵黄レシチンを40℃で8h加水分解したところ, 回収物リン脂質画分中のDHA濃度が, 基質であるDHA強化卵黄レシチンのリン脂質画分中のDHA濃度の3倍以上にまで達した。
  以上の結果より, 水分活性を調節したLipozyme IMを用いた部分加水分解により機能性リン脂質の効果的な濃縮が可能であることが明らかとなった。

書籍等出版物

• 生体におけるリン脂質の性状と機能性

  細川, 雅史, 菅原, 達也, 機能油脂懇話会 
  建帛社 2020年10月 (ISBN: 9784767962153) vi, 141p
• 水産生物機能性成分の研究論文概要集 : 水産生物機能性成分と研究動向

  細川, 雅史 
  日本水産油脂協会 2016年07月 vi, 50p
• 「第7章2 カロテノイドの吸収と代謝」、宮澤陽夫編、「食品機能性成分の吸収・代謝機構」

  細川雅史 
  シーエムシー出版、東京 2013年 p215-223
• Chapter 15 Chemopreventive effects of astaxanthin on inflammatory bowel disease and inflammation-related colon carcinogenesis. Editor, O Sommerburg, W Siems, K Kraemer . “Carotenoids and vitamin A in translational medicine”.

  M. Hosokawa, Y. Yasui 
  Boca Raton, USA.. 2013年 p293-308.
• 第6章1-7 脂溶性色素、日本油化学会編、「油脂・脂質・界面活性剤データブック「I編 油脂・脂質」

  細川雅史 
  丸善、東京 2012年 p228-234
• Omega-3 oils : applications in functional foods

  Hernandez Ernesto M, 細川 雅史 
  AOCS Press 2011年
• Omega-3 oils : applications in functional foods

  Hernandez, Ernesto M., 細川, 雅史 
  AOCS Press 2011年 (ISBN: 9781893997820) v, 305 p.
• 褐藻脂質中に含まれるフコキサンチンの抗肥満および抗糖尿病作用

  細川, 雅史 
  日本水産油脂協会 2010年 21p
• The Encyclopedia of Industrial Biotechnology

  John Wiley & Sons, Inc. 2010年
• Biocatalysis and Biomolecular Engineering

  John Wiley & Sons, Inc. 2010年
• Handobook of seafood quality, safety and health application.

  Wiley-Blackwell 2010年
• 油脂・脂質の基礎と応用−栄養・健康から工業まで−（改定第2版）

  日本油化学会 2009年
• Nutrigenomics and proteomics in health and disease

  Wiley-Blackwell 2009年
• 油脂・脂質の基礎と応用－栄養・健康から工業まで－（改定第2版）

  日本油化学会 2009年
• カロテノイドの科学と最新応用技術

  シーエムシー出版 2009年
• Biocatalysis and Agricultural Biotechnology

  CRC Press Taylor & Francis 2009年
• 水産物由来の脂溶性成分による脂肪細胞のライフサイクル制御機能の解明

  細川, 雅史 
  [北海道大学] 2008年04月 1冊
• Composition, functionality and potential applications of seaweed lipids.

  John Wiley & Sons, Inc 2008年
• Enzymatic production of marine-derived protein hydrolysates and their bioactive peptides for use in foods and nutraceuticals.

  John Wiley & Sons, Inc 2008年
• Antiobesity effect of fucoxanthin from edible seaweeds and its multibiological functions.

  ACS 2008年
• Cancer: Disease Progression and Chemoprevention

  Research Signpost 2007年
• Biocatalysis and biotechnology for functional foods and industrial products

  CRC Press Taylor & Francis 2007年
• Marine Nutraceuticals and Functional Foods

  CRC Press Taylor & Francis 2007年
• Cancer: Disease Progression and Chemoprevention

  Research Signpost 2007年
• Biocatalysis and biotechnology for functional foods and industrial products

  CRC Press Taylor & Francis 2007年
• Nutraceutical and Specialty Lipids and their Co-Products

  CRC Press Taylor & Francis 2006年
• Nutraceutical and Specialty Lipids and their Co-Products

  CRC Press Taylor & Francis 2006年

担当経験のある科目（授業）

分子栄養学北海道大学
栄養化学（2019年-）北海道大学
生化学1北海道大学
生化学２（2018年）北海道大学
食品化学実験北海道大学
食品栄養学実験北海道大学

所属学協会

• マリンバイオテクノロジー学会   日本食品科学工学会   日本肥満学会   日本栄養食糧学会   脂質生化学研究会   脂質栄養学会   日本油化学会   日本農芸化学会   アメリカ油化学会   日本水産学会   

共同研究・競争的資金等の研究課題

• 植物/海藻ベースn-3脂肪酸からEPA/DHAの細胞内自己強化を促進する食品成分の探索戦略

  日本学術振興会：科学研究費助成事業

  研究期間 : 2023年06月 -2026年03月 

  代表者 : 細川 雅史
• 褐藻由来フコキサンチンの代謝疾患予防機構における免疫細胞の機能制御の解明

  日本学術振興会：科学研究費助成事業 基盤研究(B)

  研究期間 : 2021年04月 -2024年03月 

  代表者 : 細川 雅史

   

  2021年度の研究において、以下の研究成果を得た。 (1)フコキサンチンを投与した肥満マウスの脂肪組織では、これまで報告しているように活性化マクロファージマーカーのF4/80およびM1マクロファージマーカーのCD11cのmRNA発現量の低下が確認された。さらに、M1マーカー(CD11c)/M2マーカー(Arg1)比も低下したことから、フコキサンチンがマクロファージの脂肪組織への浸潤を抑制するとともに、極性変化にも関わることが推察された。一方、T細胞マーカーを解析した結果、CD8に加えCD25およびCD4のmRNA発現量が低下し、T細胞サブセットへの影響が示唆された。(2)非アルコール性脂肪肝炎を誘導したマウスの肝臓では、フコキサンチンの投与によりCD8およびCD25のmRNA発現量が低下傾向を示した。(3)肝細胞およびマクロファージ株をフコキサンチン代謝物のフコキサンチノールで処理し、各オルガネラにおける蓄積をHPLCにて定量した。細胞膜、ミトコンドリア、ミクロソーム画分でフコキサンチノールが検出されたことから、細胞膜を通過しオルガネラへの移行することが推察された。特に、ミトコンドリア画分での蓄積が多いことが示唆された。(4)フコキサンチノールがミトコンドリア画分に蓄積していた点に着目し、ミトコンドリア機能に関わるミトコンドリアDNA量の測定を行った。NASHモデルマウスの肝臓からDNAを抽出し測定を行った結果、普通食群と比較してNASH誘導色群でみられたミトコンドリアDNA量の低下が、フコキサンチンにより抑制された。(5)エネルギー代謝に関わる白色脂肪組織から褐色脂肪組織への転換メカニズムとして分泌因子を介した細胞間コミュニケーションについて調べた。その結果、BMPを介した組織転換制御の可能性が認められた。
• Enzymatic conversion of kelp biomass for biofuels and health beneficial products.

  日本学術振興会：科学研究費助成事業 基盤研究(B)

  研究期間 : 2020年04月 -2024年03月 

  代表者 : FOX BRIAN, 高須賀 太一, 細川 雅史, 栗原 秀幸

   

  Our aim of the current project is to develop an efficient method to depolymerize natural kelps available in the Hokkaido ocean by a combination of several enzyme functions, including laminarin-degrading enzymes and alginate-degrading enzymes. A set of kelp spp. were obtained and ready to analytically evaluate their chemical compositions for the next fiscal year. Regarding a laminarin-degrading enzyme, we had picked up a glycoside hydrolase 55 enzyme (GH55) from a highly cellulolytic insect symbiont bacterium (Bianchetti and Takasuka et al., 2015, Journal of Biological Chemistry). 7 polysaccharide lyases 18 enzymes (PL18s), which function in alginate degradation, were selected from 7 different bacterial species, and four PL18s had been recombinantly expressed and subjected to the initial enzyme screening by using pure alginic acid substrate. Moreover, two polysaccharide lyase 17 enzymes (PL17s), were gene synthesized and cloned into the bacterial expression vector. From the previous studies, PL18 is shown to be the endo-type polysaccharide lyase, which produces oligoalginic acids (>3 degrees of polymerization (DP)), while PL17 should catalyze an exo-type reaction. In the FY2021, collected kelps will be tested to be hydrolyzed by at least three different enzymes, GH55, PL17, and PL18, and end products will be analyzed.
• 海洋性カロテノイドの代謝物解析と臓器・細胞連関制御を介した生活習慣病予防の新展開

  日本学術振興会：科学研究費助成事業 基盤研究(B)

  研究期間 : 2018年04月 -2021年03月 

  代表者 : 細川 雅史, 岡松 優子

   

  (1)海洋性カロテノイドのフコキサンチンを経口投与した非アルコール性脂肪肝炎(NASH)誘導マウスでは、肝臓の脂肪蓄積に加え炎症性因子のmRNA発現の抑制が見られた。さらに、線維化進行に関わる因子の発現抑制も観察された。これらの成果は、フコキサンチンの新たな健康機能としてNASH予防効果を示唆するものである。また、NASH誘導マウスの肝臓においても、フコキサンチン開裂物のパラセントロンが検出された。 (2)パラセントロンに加え、フコキサンチンの部分構造をもつ開裂物のapo-10’-fucoxanthinalやC28-allenic ketoneがマクロファージ様RAW264.7細胞に対して炎症性サイトカインの産生を顕著に抑制し、作用機構としてMAPキナーゼカスケードおよびIkBのリン酸化抑制が推察された。 (3)パラセントロンまたはapo-10’-fucoxanthinalで前処理した3T3-L1脂肪細胞では、RAW264.7細胞との共培養による炎症性サイトカインやケモカインのmRNA発現が有意に抑制され、フコキサンチン開裂物の脂肪細胞とマクロファージ間の相互作用による炎症や遊走抑制作用が推察された。 (4)アスタキサンチン開裂物のapo8’-astaxanthinalは、アスタキサンチンと比較してRAW264.7細胞に対するiNOSのmRNA発現を強く抑制し、アポアスタキサンチンの優れた抗炎症作用が示唆された。 (5)褐色脂肪組織の活性化を介した抗肥満作用を明らかにするバイオマーカーとして、血中エクソソームに含まれるマイクロRNA(miRNA)に着目し網羅的解析を行なった。PET-CTによる褐色脂肪機能の測定により被験者を褐色脂肪活性が高い群と低い群に分け、血中のエクソソームmiRNA量を解析したところ、miR-122が褐色脂肪活性と逆相関を示すことを見出した。
• 東北地方のノリ養殖に特化したスサビノリ低温耐性株の開発

  日本学術振興会：科学研究費助成事業 基盤研究(B)

  研究期間 : 2015年04月 -2018年03月 

  代表者 : 三上 浩司, 細川 雅史, 横山 雄彦, 柿沼 誠, 加藤 敦之

   

  東北地方は、大規模なノリ養殖の北限であり、ノリ収穫期の春先に海水温が5℃以下に低下することでスサビノリの生長が抑制されるため、十分な収穫量が得られない問題を抱えている。そのため、寒冷地でのノリ生産量向上を可能にするスサビノリ新品種の作出を試みた。 まず低温耐性株「豊浜赤スサビノリ」を選抜し、これが低温を含めた広い温度範囲で高成長を示す優良品種であることを明らかとした。そのため、宮城県漁業組合が養殖に用いている気仙沼スサビノリとの交雑を行った。その結果、両親株とは異なる形質を持つ株を複数得ることができた。今後はこれらの生理学的特性を解析し、東北地方のノリ養殖に適したスサビノリ品種を開発したい。
• 海洋性カロテノイドによる脂肪細胞の褐色化を介したメタボリック症候群予防機構の解明

  日本学術振興会：科学研究費助成事業 基盤研究(B)

  研究期間 : 2015年04月 -2018年03月 

  代表者 : 細川 雅史, 岡松 優子, 勝木 曉美, 大内 裕佳, 田谷 大輔, 立山 莉帆, 秋田 知輝

   

  褐藻中に特徴的に含まれるフコキサンチンは、食餌性肥満誘導マウスの褐色脂肪組織に加え、白色脂肪組織（WAT）においてUCP1(脱共役タンパク質1)を含むミトコンドリア因子の発現増加による褐色化を誘導し、脂質代謝の活性化を伴ってWAT重量の増加を抑制した。フコキサンチン代謝物によるミトコンドリア因子の発現増加は脂肪細胞においても観察され、その調節因子としてPGC-1αの重要性が推察された。一方、褐色化に関わるベージュ脂肪細胞の数が、脂肪組織中のプロジェニター細胞により規定される可能性が高く、その数が加齢に伴い減少することを基礎知見として見出した。
• バイオ燃料生産性を飛躍させる光エネルギー駆動型マリンビブリオファクトリーの創成

  日本学術振興会：科学研究費助成事業 挑戦的萌芽研究

  研究期間 : 2014年04月 -2016年03月 

  代表者 : 澤辺 智雄, 細川 雅史

   

  より効率的に海藻原料をバイオ燃料へと生物変換するために，「光エネルギー」を効果的に利用する生物触媒の開発を目的として，①Nonlabens sediminisが有するプロテオロドプシン遺伝子の発現、②新規カロテノイド生合成遺伝子群の収集とクローニングを行った。また，マリンビブリオで適応可能な効率な遺伝子改変システムの開発に向け，マリンビブリオにおけるCRISPR/Casシステムの特徴を調べた。
• マリンビブリオを核とした海洋バイオ水素生産技術のビッグバン

  日本学術振興会：科学研究費助成事業 基盤研究(B)

  研究期間 : 2013年04月 -2016年03月 

  代表者 : 澤辺 智雄, 細川 雅史, 中川 聡

   

  高い水素生成能を有するマリンビブリオを生物触媒として，①連続的かつ安定的なバイオ水素生産を達成するための連続培養系の構築，および②発酵残滓の高付加価値化を検討し，①マンニトールを基質として70日間にわたり連続的に水素の生成が可能な培養系の構築，②2種類のマリンビブリオ生物触媒を利用した，アルギン酸‐水素生成システムの構築，および③種々の新規・希少カロテノイド生合成遺伝子資源の獲得に成功した。
• 海産軟体動物および藻類に含まれる脂溶性成分の抽出と特性分析および生活習慣病予防機能の評価

  国際的な科学技術共同研究などの推進 国際科学技術共同研究推進事業 SICORP ニュージーランド

  研究期間 : 2015年 -2016年 

  代表者 : 細川 雅史

   

  (1) 本研究は、ニュージーランド産の軟体動物や海藻などの水産物、並びに藻類に含まれる脂溶性成分の特性を明らかにするとともに、抗肥満、抗糖尿病、炎症性腸疾患予防効果を見出すことを目的とする。更に、機能脂質成分の効率的な抽出法や強化養殖法について検討する。(2) 具体的には、ニュージーランド側が藻類や軟体動物から抽出物を得て、一部を日本側へ送付する。独自に確立した分析法により、日本側ではフラン酸や複合脂質、カロテノイド組成の分析と構造解析を行い、ニュージーランド側はオメガ-3脂肪酸やリゾルビン誘導体の分析を行う。日本側では、抽出物および分離した機能性脂質を用いて、細胞および動物実験によりそれらの抗肥満や抗糖尿病、炎症性腸疾患予防効果を評価する。一方、ニュージーランド側は機能性物質の効率的な抽出法や生産量の増加を目指して、水産軟体動物への飼料の開発やフォトバイオリアクターを用いた藻類養殖法の開発をはかる。(3) 本研究で日本とニュージーランドが交流を通じて、水産物中に含まれる脂質成分の新たな健康機能性の解明と産業利用にむけた生産法の開発に取り組む。これによって、両国を含め世界的に問題となっている生活習慣病予防へニュージーランド産水産物の利用が期待できるとともに、水産業の活性化につながる。更に、本プロジェクトでは日本側の若手研究者を含めた研究交流活動、ならびに両国のプロジェクト研究者に加え、関連する国内外の研究者を含めた研究セミナーを開催することで機能性食品と水産業の発展に向けた情報交換を積極的に進める。これによって、日本とニュージーランドの継続的な研究交流と共同研究体制を構築が期待される。
• アレンカロテノイドの生体内局在と機能解析

  日本学術振興会：科学研究費助成事業 基盤研究(B)

  研究期間 : 2011年04月 -2014年03月 

  代表者 : 宮下 和夫, 細川 雅史

   

  内臓WATでのUCP1の発現に基づくフコキサンチンの抗肥満作用の分子機構を解明した。フコキサンチンによるUCP1の発現誘導は、フコキサンチンの特異な構造、すなわち、アレン結合と、カロテノイド鎖の両側に結合した官能基を多数有する２個の６員環の存在に起因していることも明らかにした。したがって、その他のアレンカロテノイドやフコキサンチンの分解産物ではこうした作用は見られなかった。フコキサンチンはインスリン抵抗性を改善し、抗糖尿病作用も示した。また、筋肉でのGLUT4の発現増大とその細胞膜の促進がフコキサンチンの抗糖尿病作用の重要な分子機構であることを見出した。
• 海洋性カロテノイドの慢性炎症疾患予防作用の基盤となる組織・細胞間調節機能の解明

  日本学術振興会：科学研究費助成事業 基盤研究(B)

  研究期間 : 2011年04月 -2014年03月 

  代表者 : 細川 雅史, 安井 由美子

   

  フコキサンチンは、ケモカインによる脂肪細胞と免疫細胞の相互作用を制御し、肥満脂肪組織での慢性炎症を抑制した。更に、脂肪組織由来の炎症性因子の産生抑制とともに、骨格筋組織における糖代謝を改善した。一方、ヘマトコッカス藻由来のアスタキサンチンが、潰瘍性大腸炎や大腸発癌のモデル系において予防効果を発揮した。その予防機構として、組織細胞に対する直接的な抗炎症作用に加え、マクロファージによる大腸細胞の炎症誘導に対する抑制効果を見出した。以上のように、海洋性カロテノイドは細胞・組織への直接的な作用に加え、それらの相互作用を制御し、効果的に慢性炎症や炎症性疾患の予防に貢献するものと推察する。
• バイオマス燃料生産に適する最少遺伝子セットを持つマリンビブリオセルの創成

  日本学術振興会：科学研究費助成事業 挑戦的萌芽研究

  研究期間 : 2011年 -2013年 

  代表者 : 澤辺 智雄, 細川 雅史, 中川 聡

   

  再生可能な新エネルギーの開発に向けて、海洋バイオマス由来のバイオ燃料の開発は技術基盤の成熟が待たれている。本研究では、海藻糖質を基質にバイオエタノール生産能を示すマリンビブリオに着目し、トランスクリプトーム、代謝産物解析、および合成生物学的代謝改変技術を導入し、バイオマス燃料生産に適する最少の遺伝子セットを持つビブリオセルの創成を行った。
• 新規な生体親和性化粧品素材ホスファチジル-パンテノールの機能開発

  産学が連携した研究開発成果の展開 研究成果展開事業 研究成果最適展開支援プログラム(A-STEP) 探索タイプ

  研究期間 : 2011年 -2012年 

  代表者 : 細川 雅史

   

  本事業では、酵素的合成法にて高収率での調製が可能になったホスファチジル-パンテノールの優れた抗炎症作用を評価することを目標とした。ホスファチジル-パンテノールは、活性化したマクロファージに対して炎症性サイトカインであるIL-6やIL-1β、TNFα、炎症性酵素であるCOX-2やiNOSのmRNA発現やタンパク質産生を抑制した。その効果は従来のパンテノールと比較して4-10倍以上高い活性であり、少量で抗炎症作用を発揮する優位性をもった新規物質であることが明らかとなった。特に、ホスファチジルパンテノールの優れた抗炎症作用に関わる分子機構として、NF-κBやAP-1など複数の炎症誘導因子に対して制御機能を示すことを見出し、新規化粧品素材としての有効性を実証した。
• 化学合成細菌の光刺激によるカロテノイド生合成系の活性化と制御

  日本学術振興会：科学研究費助成事業 挑戦的萌芽研究

  研究期間 : 2011年 -2012年 

  代表者 : 細川 雅史

   

  本研究では、海藻から分離した11ShimoA1(A1)株が新規カロテノイドである2'-isopentenylsaporxanthinを合成し、その生合成系が青色光(470nm)の刺激によって活性化することを見出した。A1株は、カロテノイド合成に関わるcrtB、crtI、crtY、crtZ遺伝子を有し、それらがクラスターを形成していることを明らかにした。更に、A1株に特徴的なprenyltransferaseおよびphytoenedesaturaseの存在を見出すとともに、これらの遺伝子が青色光刺激によって発現増加することを明らかにした。
• 海洋性カロテノイドの抗炎症作用をターゲットとした生活習慣病予防機能の解明

  日本学術振興会：科学研究費助成事業 基盤研究(B)

  研究期間 : 2008年 -2010年 

  代表者 : 細川 雅史, 安井 由美子

   

  アスタキサンチンが、潰瘍性大腸炎や大腸発癌に対して予防効果を示すことを見出した。その作用機構として、アスタキサンチンが大腸組織においてNF-κBの活性化抑制を介して炎症性サイトカインの遺伝子発現を制御することが推察された。一方、褐藻に含まれるフコキサンチンは、内臓脂肪の増加抑制と血糖値改善効果を示す。フコキサンチンは脂肪組織における炎症性アディポサイトカインの遺伝子発現を抑制するとともに、炎症に関わるマクロファージの浸潤を抑制し脂肪細胞とマクロファージの相互作用を調節することを見出した。
• 抗糖尿病作用を示すキサントフィルの簡易濃縮法の開発

  産学が連携した研究開発成果の展開 研究成果展開事業 地域事業 地域イノベーション創出総合支援事業 シーズ発掘試験

  研究期間 : 2009年 -2009年 

  代表者 : 細川 雅史

   

  ワカメなどに含まれるキサントフィルは、血糖値改善効果を有し、抗糖尿病効果が期待される。本研究では、キサントフィルとその他の成分の溶媒への溶解性の差を利用した簡便な濃縮法を開発する。具体的には、水産物から抽出した脂溶性成分を、溶媒混合物に溶解して二層分離した後、一方からキサントフィル濃縮物を回収するという極めて簡便な方法である。これにより、10-30%以上まで濃縮したキサントフィル素材の調製法を開発する。
• 水産物由来の脂溶性成分による脂肪細胞のライフサイクル制御機能の解明

  日本学術振興会：科学研究費助成事業 基盤研究(C)

  研究期間 : 2005年 -2007年 

  代表者 : 細川 雅史

   

  本研究では、水産物に特徴的なカロテノイドや高度不飽和脂肪酸に着目し、肥満形成と密接な関わりを持つ脂肪細胞のライフサイクル制御機能に焦点を絞り検討した。マウス由来の前駆脂肪細胞3T3-L1を用いて、脂肪細胞への分化を抑制する物質の探索を行った結果、食用海藻であるワカメやコンブなどに含まれるフコキサンチンが、分化過程で誘導されるグリセロール-3-リン酸脱水素酵素(GPDH)活性や細胞内の脂肪蓄積を顕著に抑制することを見出した。更に、フコキサンチンを経口投与したマウスの白色脂肪組織で検出されたフコキサンチノールにおいても、同様の分化抑制能を示すことを明らかにした。その際、フコキサンチン及びフコキサンチノールは、脂肪細胞への分化の過程でマスターレギュレーターとして働くPPARγの発現を抑制することを見出した。また、フコキサンチンは、肥大化した脂肪細胞で過剰に発現しインスリン抵抗性を引き起こすTNFαの遺伝子発現を顕著に抑制するとともに、糖尿病肥満マウスの血糖値の改善効果を示した。これらの結果は、フコキサンチンが脂肪細胞のライフサイクルを制御することによって、白色脂肪組織の機能を改善することを示唆するものである。 一方、水産脂質に特徴的なドコサヘキサエン酸(DHA)やエイコサペンタエン酸(EPA)も、3T3-L1細胞やラットより分離した初代脂肪細胞の分化をPPARγやC/EBPαの発現抑制を介して抑制することを見出した。また、有効性を明らかにしたDHAやEPAを含有する魚油とフコキサンチンを併用することで、糖尿病肥満マウスの内臓脂肪の増大をより効果的に抑制できることを見出した。 以上の結果は、フコキサンチンやDHA、EPAが脂肪細胞のライフサイクル制御能を有し、肥満予防への利用が期待できる新たな水産成分であることを示唆するものである。
• 高い生体適合性と機能性をもつ新規共役脂肪酸リン脂質の合成法の開発と実用化研究

  産学が連携した研究開発成果の展開 研究成果展開事業 地域事業 地域イノベーション創出総合支援事業 シーズ発掘試験

  研究期間 : 2006年 -2006年 

  代表者 : 細川 雅史

   

  本研究では、優れた生活習慣病予防機能を有し且つ幅広い用途での利用が期待できる共役型脂肪酸含有リン脂質の酵素的新規合成法の開発を試みる。特に、ホスホリパーゼ、リパーゼを利用した機能性リン脂質の合成反応に関して、?リン脂質の所望の位置への共役型脂肪酸の精密合成反応、?リン脂質の塩基構造をセリンやグリセロールに変換するリン酸基転移反応法について検討することで、本研究の実用化への見通しを得る。
• 脂溶性機能成分の単分散マイクロ/ナノスフィア化による安定性及び吸収性の向上

  日本学術振興会：科学研究費助成事業 基盤研究(B)

  研究期間 : 2004年 -2006年 

  代表者 : 宮下 和夫, 細川 雅史

   

  1.エイコサペンタエン酸(EPA)、ドコサヘキサエン酸(DHA)などの高度不飽和脂肪酸及びこれらを含む油脂の酸化は、エマルションを形成する脂質分散粒子の粒子径と界面の性質に大きく依存することを明らかにした。一般に、DHAやEPAを多く含む魚油は、リノール酸を主体とする植物油に比べてバルク系(油脂そのものを放置した系)では非常に酸化されやすいが、エマルション系では、特にその粒子径が小さい場合、場合によっては魚油の方が植物油よりも安定となることを示し、その理由を明らかにした。 2.エマルション中での酸化安定性は乳化剤の影響を強く受けることを明らかにした。食品に一般的に用いられるショ糖エステルとポリグリセリンエステルの影響について検討したところ、HLBが高くなるほど、また、構成脂肪酸の鎖長が長い程高度不飽和油脂の酸化安定性が高くなることを明らかにした。 3.高度不飽和脂肪酸の酸化抑制に多用される抗酸化剤の効果について、その界面での存在状態に着目した検討を行ったところ、抗酸化剤が界面付近あるいは油層により多く存在するほど(水相中での存在量が少ないほど)、抗酸化剤の効果がより強く発揮されることが明らかになった。 4.高度不飽和脂質をはじめとする機能性脂質を含むマイクロ/ナノスフィアは、界面の化学的特性を制御することにより酸化安定性を向上できるだけでなく、生体にとって吸収されやすい形態であることが明らかになった。
• 核内転写因子の発現を制御する高度不飽和リン脂質に関する研究

  日本学術振興会：科学研究費助成事業 若手研究(B)

  研究期間 : 2002年 -2003年 

  代表者 : 細川 雅史

   

  昨年度の研究において、DHA含有ホスファチジルエタノールアミン(DHA-PE)がdibutyrylcAMP(dbcAMP)によるヒト白血病HL-60細胞の分化誘導を顕著に亢進することを明らかにした。更にその過程で核内転写因子のAP-1を構成するc-Junタンパク質の発現増加を確認した。AP-1は、c-Jun/c-Junのホモダーマーまたはc-Jun/c-Fos、c-Jun/ATF-2のヘテロダイマーによって構成され、MAPキナーゼにより活性化されることで分化に関連する遺伝子を発現する。これらの結果を踏まえ、本年度は以下の点を明らかにした。 1.DHA-PEとdbcAMPを併用した場合c-Fosタンパク質並びにそのmRNAの強い発現がみられたが、dbcAMPの単独処理におけるc-Fos発現量との間に大きな差が見られなかった。よって、dbcAMPによる分化の誘導にはc-Fosおよびc-Junの双方が重要な役割を果しているが、DHA-PEとの併用効果に発現にはc-Junタンパクがキーレギュレーターとなっていることが示唆された。 2.DHA-PEとdbcAMPにより併用処理したHL-60細胞では、MAPキナーゼの一つであるJNKが培養初期において一過的に活性化された。これによってAP-1の転写活性も高められ、分化に関連する遺伝子の発現が亢進されることが示唆された。 3.DHAをリガンドとすることが知られている核内受容体のペルオキシソーム増殖薬応答性受容体(PPAR)γの発現への影響を調べたが、その発現への影響は認められなかった。 以上の結果から、DHA-PEは分化誘導物質であるdbcAMPと併用することにより、c-Junの発現亢進とJNKの活性化により核内転写因子AP-1の転写活性を高め、ヒト白血病HL-60細胞への分化誘導効果を亢進することが示唆された。
• DHA結合型リン脂質の構造と白血病細胞の分化誘導機構に関する研究

  日本学術振興会：科学研究費助成事業 奨励研究(A)

  研究期間 : 1997年 -1998年 

  代表者 : 細川 雅史

   

  1. DHA結合型リン脂質の分化誘導促進効果:(1)シロサケ筋肉,精巣及びマイカ肝膵臓から抽出した水産リン脂質が,ヒト白血病(HL-60)細胞に対するレチノイン酸やジブチリルcAMPなどの分化誘導剤の作用を増強する効果,すなわち分化誘導促進能を有することが明らかとなった。(2)マウス白血病(M1)細胞に対しては,DHA結合型リン脂質単独においても分化誘導能が認められた。(3)分化誘導促進効果は,DHAの遊離脂肪酸形態に比べリン脂質形態,特にPE形態において顕著なものであったことから,機能発現にはリン脂質形態が重要であると推察された。 2. 細胞膜への影響:TNBSクエンチング法並びに脂肪酸組成分析におけるDHA含有率の上昇から,DHA結合型リン脂質がHL-60細胞内に取り込まれていることを確認した。 3. 機能遺伝子発現への影響:DHA結合型PEは,レチノイン酸の分化誘導過程において重要な役割を果たすレチノイドXレセプタ-α(RXRα)のmRNA量を増加させることが示唆された。 4. 細胞内情報伝達酵素への影響:DHA結合型リン脂質の分化誘導促進作用がプロテインキナーゼ阻害剤により抑制されたことから,分化誘導促進能はプロテインキナーゼを介した作用であることが示唆された。 以上の結果から,水産リン脂質を含めたDHA結合型リン脂質が白血病細胞に対して分化誘導能及び分化誘導促進能を有することが明らかとなった。機能発現にはリン脂質の構造が重要であり,細胞に取り込まれた後,細胞内情報伝達酵素や核レセプターの発現を介して分化誘導剤の作用を促進することが推察された。
• ガン細胞の増殖、分化に及ぼすDNA含有リン脂質の影響に関する研究

  日本学術振興会：科学研究費助成事業 奨励研究(A)

  研究期間 : 1995年 -1995年 

  代表者 : 細川 雅史

   

  酸素反応により種々のドコサヘキサエン酸(DHA)含有リン脂質を調製し、ヒト前骨髄性白血病細胞(HL-60細胞)の増殖、分化に及ぼす影響について検討した。 1.種々のDHA含有ホスファチジルコリン(PC)分子種をHL-60細胞培養液に添加して、あらかじめ24時間培養することにより、レチノイン酸(RA)の細胞分化誘導能が増強された(細胞分化誘導促進効果)。その効果はDNA含有PC分子種により異なり、1-Pal,2-DHA-PC及び1-Ole,2-DHA-PCにおいて顕著であった。 2.DHA含有PCの細胞分化誘導促進効果は濃度依存的に上昇し、それに伴い細胞内のDHA含量の増加が見られた。DHAの結合していないdi-Pal-PC、di-Ole-PC及び大豆PCには促進効果が見られなかった。 3.DHA含有リン脂質の化学形態の影響について検討したところ、同一分子種ではPCに比べ、ポスファチジルエタノールアミン(PE)、ホスファチジルセリン(PS)の形態において細胞分化誘導能の増強作用が大きく、特に1-Pal,2-DHA-PE及び1-Ole,2-DHA-PEにおいて細胞分化誘導促進効果が顕著であった。更に、DHA含有PE自体にも分化誘導作用が見られた。 4.HL-60細胞の増殖に及ぼすDHA含有リン脂質分子種の影響についても検討を行ったところ、DHA含有PEの形態において増殖抑制効果が大きかった。 以上の結果より、DHA含有リン脂質がガン細胞の分化誘導促進能や増殖抑制能を有し、その効果がリン脂質の分子種や化学形態によって異なることが明らかとなった。特に、1-Pal,2-DHA-PE及び1-Ole,2-DHA-PEの効果が顕著であったことから、制ガン剤の減量とともに副作用の軽減への利用が期待される。
• 赤血球の変形能に及ぼす高度不飽和脂肪酸含有リン脂質の影響に関する研究

  日本学術振興会：科学研究費助成事業 奨励研究(A)

  研究期間 : 1994年 -1994年 

  代表者 : 細川 雅史

   

  1.赤血球の変形能をシリコン単結晶基板マイクロチャンネルを用いて測定することにより、再現性の高い測定結果が得られた。 2.リパーゼやホスホリパーゼを用いて合成したEPA,DHA含有ホスファチジルコリン(PC)は、赤血球にとり込まれることによりその変形能を向上させることを証明した。 3.エタノールアミン結合リン脂質ではsn-2位にDHAを含むものが、セリン結合リン脂質ではsn-1位にEPAを含むものが赤血球の変態能を大きく向上させることも証明できた。 4.リン脂質クラス間を比較すると、エタノールアミン結合リン脂質はコリン結合リン脂質およびセリン結合リン脂質よりも、赤血球変形能を向上させる作用が強いことを認めた。特に、sn-2位にDHAを含むエタノールアミン結合リン脂質が赤血球の変形能を最も向上できることが示唆された。 5.蛍光偏光解消法により赤血球膜の流動性を測定したところ、膜の流動性向上は赤血球の変形能の向上とよく対応していた。 6.鮭卵より調製したEPA,DHA含有リン脂質においても赤血球変形能の向上作用がみられた。 7.リノール酸を主な脂肪酸とする大豆リン脂質は赤血球の変形能を改善しなかった。また、水素添加したリン脂質は赤血球の変形能を明かに低下させた。 以上の結果により、EPA,DHA含有リン脂質が赤血球の変形能を向上させ、その作用の強弱が分子種や脂質形態によって異なることが明かとなった。血栓症などの成人病予防が大きな課題となっている今日、EPA,DHA含有リン脂質を合成し、機能の一部を分子種レベルで明かにできたことは意義のあることと考える。
• 赤血球膜流動性におよぼす高度不飽和脂肪酸含有複合脂質の影響に関する研究

  日本学術振興会：科学研究費助成事業 奨励研究(A)

  研究期間 : 1993年 -1993年 

  代表者 : 細川 雅史

   

  1.ブタ膵臓ホスホリパーゼA_2によるsn-2位にEPA,DHAを含むホスファチジルコリンの合成、LipozymeIM60によるsn-1位にEPAを含むホスファチジルコリンの合成、Streptomyces sp.由来のホスホリパーゼDによるこれらのホスファチジルコリンのホスファチジル基転移を行うことができきた。これによりホスファチジルコリンと同一の脂肪酸残基をもつ高度不飽和脂肪酸含有ホスファチジルエタノールアミンとホスファチジルセリンの合成物を得ることができた。 2.コリン結合リン脂質に比べアミノ基結合リン脂質のほうが赤血球により導入されやすいことを明らかにできた。 3.TNBSクエンチング法により、赤血球にとり込まれたリン脂質の40〜50%は膜タンパク質近傍に存在することを示すことができた。 4.高度不飽和脂肪酸含有ホスファチジルエタノールアミンはほとんど溶血性を示さないことがわかった。 5.水素添加したリン脂質は赤血球膜の流動性を明らかに低下させることを確認できた。 6.大豆リン脂質は赤血球膜の流動性を改善できないことがわかった。 7.合成したEPA,DHA含有リン脂質はいずれも赤血球膜流動性を改善する作用のあることが確認された。 8.コリン結合リン脂質、アミノ基結合リン脂質はいずれもEPA,DHAをsn-2位に含む混合形態の場合に最も高い赤血球膜流動性改善効果を示すことがわかった。 9.同一の脂肪酸残基の場合、コリン結合リン脂質はアミノ基結合リン脂質よりも赤血球膜の流動性改善効果が低いことをみとめた。 以上の結果より判断し、高度不飽和脂肪酸含有リン脂質は赤血球膜の流動性を高めて赤血球の変形能を向上させ、ひいては高血圧症や血栓症の予防や治療に役立つことも期待できることが明かとなった。
• 高度不飽和脂肪酸含有リン脂質の酵素的合成とその生理作用に関する研究

  日本学術振興会：科学研究費助成事業 一般研究(C)

  研究期間 : 1992年 -1993年 

  代表者 : 高橋 是太郎, 細川 雅史, 羽田野 六男

   

  sn-1位に高度不飽和脂肪酸を結合するリン脂質の合成を試み,次の知見を得た. 1.中間水分活性域以上の反応系中の水分はリン脂質への高度不飽和脂肪酸導入の初速度を速めるが,加水分解を同時に促進し,収率の低下をまねくこと. 2.低水分活性域ではリン脂質への高度不飽和脂肪酸導入速度は非常に遅いが,比較的高収率が得られること. 3.反応系中の水分の高精度制御とポリアルコーの併用によって,理論上の上限までリン脂質のsn-1位に高度不飽和脂肪酸を導入でき,且つ最大80%の回収率を得られること. ついでsn-1位に高度不飽和脂肪酸を結合するリン脂質の生理活性について検討し,血清存在下でsn-1位にEPAを結合するPCはその濃度が10μg/ml培地のとき,レチノイン酸単独の場合のヒト前骨髄性白血病細胞(HL-60細胞)分化誘導作用に比べ,レチノイン酸量約10倍に相当する細胞分化誘導効果を有することが認められた.これはsn-2位に高度不飽和脂肪酸を結合するリン脂質のヒト前骨髄性白血病細胞(HL-60細胞)分化誘導促進作用とほぼ同一レベルであった. 今後は個々の脂質クラス,分子種について高度不飽和脂肪酸を組かえて生理活性の評価を行う予定である.分子種と生理作用との間の構造機能相関を見いだすことを最終目標に考えている.
• Highly utilization of marine biofunctional materials

産業財産権

• 血糖値上昇抑制剤

  特開２００７－２９７３７０
• フコキサンチノールの製造方法

  特願2005-340997
• 生体内ＤＨＡ合成促進剤

  特開２００７－７７０６７
• 抗腫瘍剤

  特願2004-060821.