研究者情報

マスター

アカウント（マスター）

• 氏名

  別府　史章(ベツプ　フミアキ), ベツプ　フミアキ

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Ⅱ, Advanced Marine Bioresources Chemistry Ⅱ, 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, 生化学Ⅰ, Biochemistry Ⅰ, 学士課程, 水産学部, 生体分子、水、タンパク質、糖質、脂質、核酸
• 2021, 食品栄養学実験, Laboratory Work on Nutritional Biochemistry, 学士課程, 水産学部, 食品、栄養成分、タンパク質、糖質、脂質、水分、灰分

researchmap

プロフィール情報

所属

• 北海道大学, 大学院水産科学研究院 海洋応用生命科学部門 生物資源化学分野, 准教授

学位

• 博士（水産科学）（北海道大学）

プロフィール情報

• 姓

  別府, ベップ

• 名

  史章, フミアキ

• ID各種

  201801007026532380

所属

• 北海道大学, 大学院水産科学研究院 海洋応用生命科学部門 生物資源化学分野, 准教授

業績リスト

研究キーワード

• 脂質生化学   分子栄養学   脂質代謝   機能性脂質   ω3 高度不飽和脂肪酸   ビタミンE   

研究分野

• ライフサイエンス / 水圏生命科学 / 水産科学
• ライフサイエンス / 食品科学 / 脂質生化学 / 分子栄養学
• ライフサイエンス / 水圏生命科学 / 水産脂質化学

経歴

• 2018年04月 - 現在 北海道大学 大学院水産科学研究院 生物資源化学分野 准教授
• 2013年03月 - 2018年03月 東京海洋大学 食品生産科学部門 助教

委員歴

• 2024年04月 - 現在   日本油化学会   関東支部常任幹事
• 2024年04月 - 現在   日本栄養食糧学会 北海道支部   参与
• 2023年03月 - 現在   日本水産学会   水産教育推進委員会 拡大委員
• 2021年04月 - 現在   日本油化学会 関東支部   事業企画委員
• 2019年03月 - 2021年02月   日本水産学会   編集委員会幹事
• 2017年03月 - 2019年02月   日本水産学会   シンポジウム企画委員
• 2017年03月 - 2019年02月   日本水産学会   企画広報委員会幹事
• 2015年03月 - 2019年02月   日本水産学会   編集幹事補佐

受賞

• 2018年 日本油化学会 ベストオーサー賞
   

  受賞者: 別府 史章

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 [査読有り]
   

  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10月30日 [査読有り]
  
• 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 [査読有り]
   

  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 [査読有り]
   

  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 135318 - 135318 2022年12月28日 [査読有り]
   

  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.
• Comparison of Lipoprotein Cholesterol Levels in Golden Syrian Hamster Administrated trans-Octadecenoic Acid Positional Isomers.

  Koji Nagao, Junya Ueno, Kazuaki Yoshinaga, Toshiharu Nagai, Hoyo Mizobe, Akihiko Yoshida, Fumiaki Beppu, Seiya Tanaka, Naohiro Gotoh

  Journal of oleo science 71 4 609 - 618 2022年04月01日 [査読有り]
   

  We previously conducted a study using HepG2 cells to compare the effect on the secreted apolipoprotein B-100 and apolipoprotein A-1 ratio (B-100/A-1) corresponding to the ratio of low-density to high-density lipoprotein cholesterol (LDL/HDL) among 13 types of trans-octadecenoic acid (t-18:1) positional isomers. The results revealed that trans-5-18:1 (t5) significantly increased B-100/A-1. In this study, 1% of t5 in the diet, corresponding to 2.08 energy%, was administrated golden Syrian hamsters for 4 weeks to reveal the effects on lipid profiles, including LDL/HDL, by comparing cis-9-octadecenoic acid (OA, oleic acid), trans-9-octadecenoic acid (EA), trans-11-octadecenoic acid (VA), and trans-9,trans-12- octadecadienoic acid (TT). LDL/HDL was not significantly different among the groups. However, the cholesterol concentration of medium very low-density lipoprotein (VLDL) was significantly lower in the TT diet than in the OA and t5 diets. The cholesterol concentration of small VLDL was significantly lower in the TT diet than in the OA, t5, and EA diets. The cholesterol concentration of large LDL was significantly lower in the TT diet than in the t5 and EA diets. However, no significant difference was detected between the TT and OA diets. In contrast, the cholesterol concentration of very small HDL was significantly higher in the TT diet than in the t5 diet. These results would support that lipid metabolism is affected by the structure of TFA in animals. However, t5-18:1 did not significantly change any lipid profile compared to OA existing in nature, and the previous result from the cell experiment showing that t5 increased B-100/A-1 (LDL/HDL) was not confirmed in this animal experiment.
• 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 89 243 - 251 2022年 [査読有り]
   

  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.
• Analysis of minor vitamin E homologues in natural products

  Fumiaki Beppu, Naohiro Gotoh

  Journal of Berry Research 1 - 12 2021年09月07日 [査読有り]
   

  Fruits and seeds are naturally rich in antioxidants, which provide protection against UV light and oxygen. Vitamin E is a typical antioxidant, and offers radical scavenging activity to prevent the oxidation of the polyunsaturated fatty acids in cell membranes, contribute to homeostasis, and support the biological functions of animals and plants. Tocopherol and tocotrienol are forms of vitamin E widely found in natural products. In addition, recent studies have demonstrated the existence of minor homologues, namely tocomonoenol and tocodienol. The characteristic physiological functions of vitamin E homologues are dependent on their structure. Consequently, the nutritional functionality of the minor homologues has attracted much research interest, which relies on highly accurate analytical methods. This review aimed to summarize the literature concerning the diversity of tocomonoenol and tocodienol, as well as reports on the various methods for their analysis and detection in different sample matrices. This paper is expected to contribute to future exploratory research and the functional evaluation of minor homologues.
• 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.
• Simultaneous Treatment of Long-chain Monounsaturated Fatty Acid and n-3 Polyunsaturated Fatty Acid Decreases Lipid and Cholesterol Levels in HepG2 Cell.

  Kazuaki Yoshinaga, Yota Mizuno, Samanthika Senarath, Aya Yoshinaga-Kiriake, Toshiharu Nagai, Fumiaki Beppu, Seiya Tanaka, Naohiro Gotoh

  Journal of oleo science 70 5 731 - 736 2021年05月01日 [査読有り]
   

  The n-3 type polyunsaturated fatty acids (n-3PUFAs), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), from fish oil exhibit health benefits such as triacylglycerol- and cholesterol-lowering effects. Some pelagic fishes contain long-chain monounsaturated fatty acids (LC-MUFAs) such as eicosenoic acid (C20:1), which exert health-promoting effects. However, no study has evaluated beneficial effects of n-3PUFA and LC-MUFA combination. Here, we investigated effects of simultaneous treatment with n-3PUFA (EPA and DHA) and LC-MUFA (cis-5-C20:1 and cis-7-C20:1) and found that n-3PUFA and LC-MUFA combination significantly decreased lipid accumulation and reduced total cholesterol in HepG2 cells. Cholesterol level was significantly lower in DHA + cis-7-C20:1 group than in DHA + EPA group. These results suggest the importance of LC-MUFA as a functional molecule in fish oil.
• 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.
• Incorporation of Dietary Arachidonic and Docosatetraenoic Acid into Mouse Brain.

  Kazuaki Yoshinaga, Haruna Ishikawa, Fumiaki Beppu, Naohiro Gotoh

  Journal of agricultural and food chemistry 69 8 2457 - 2461 2021年03月03日 [査読有り]
   

  It is essential to analyze the metabolism of dietary polyunsaturated fatty acids in the brain for the research and development of functional foods. In this study, a single dose of 2,2-dideuterium-labeled docosatetraenoic acid ((+2)DTA) or 2,2-dideuterium-labeled arachidonic acid ((+2)AA) was orally administered to Institute of Cancer Research (ICR) mice and its metabolism in the brain was investigated. In the (+2)DTA group, the (+2)DTA content in the brain was significantly increased at 4, 8, 24, and 96 h compared to 0 h after administration, while in the (+2)AA group, the (+2)AA content was significantly increased at 4, 8, 24, and 96 h compared to 0 h. However, there was no significant difference in the content of (+2)DTA, a metabolite of (+2)AA, among all the groups. These results suggest that dietary (+2)DTA and (+2)AA pass through the blood-brain barrier and dietary (+2)AA is rather stored in the brain than converted to (+2)DTA.
• 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 C31 -allenic-apocarotenoid, in white adipose tissue of diabetic/obese KK-Ay and normal C57BL/6J mice fed 0.2% fucoxanthin diet for 1 week. In lipopolysaccharide-activated RAW264.7 macrophages, paracentrone as well as C26 - and C28 -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-κB inflammatory signal pathways. In contrast, β-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.
• Application of Partial Hydrogenation for the Generation of Minor Tocochromanol Homologs and Functional Evaluation of Hydrogenated Tocotrienol-rich Vitamin E Oil in Diabetic Obese Mice.

  Fumiaki Beppu, Aimi Sakuma, Satoshi Kasatani, Yoshinori Aoki, Naohiro Gotoh

  Journal of oleo science 70 1 103 - 112 2021年 [査読有り]
   

  Recent research has identified minor homologs of vitamin E with one or two double bonds in the side-chain, namely tocomonoenol (T1) and tocodienol (T2), in natural products. We first explored the effectiveness of partial hydrogenation for generating minor tocochromanols from tocotrienol (T3). During hydrogenation with pure α-T3 as a substrate, the side-chain was partially saturated in a time-dependent manner, and a large amount of α-T1 and α-T2 was obtained. To investigate the beneficial effects of the hydrogenated product, we fed diabetic obese KK-A y mice with a hydrogenated T3 mixture (HT3). Feeding HT3 revealed tissue-specific accumulation of tocochromanols, ameliorated hyperglycemia and improved ratio of high-density lipoprotein cholesterol to total cholesterol in serum, with invariant body weight and fat mass. Hence, we propose that hydrogenation is a useful method for generating T1 and T2 homologs, which can be applied to explore the structure-related function of tocochromanols.
• 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23日 [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 anti-cancer, 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 activated-hepatic 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.
• 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.
• 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15日 [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.
• 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.
• Functional evaluation of marine-derived tocopherol, a minor homolog of vitamin E, on adipocyte differentiation and inflammation using 3T3-L1 and RAW264.7 cells

  Fumiaki Beppu, Yusuke Aida, Masahiro Kaneko, Satoshi Kasatani, Yoshinori Aoki, Naohiro Gotoh

  Fisheries Science 86 2 415 - 425 2020年03月 [査読有り]
  
• The Effect of n-3 PUFA Binding Phosphatidylglycerol on Metabolic Syndrome-Related Parameters and n-3 PUFA Accretion in Diabetic/Obese KK-Ay Mice.

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

  Nutrients 11 12 2019年11月22日 [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-Ay 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-Ay 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-Ay mice.
• Preparation of n-3 Polyunsaturated Phosphatidylglycerol from Salmon Roe Lipids by Phospholipase D and In Vitro Digestion

  Chen Liping, Beppu Fumiaki, Miyashita Kazuo, Hosokawa Masashi

  EUROPEAN JOURNAL OF LIPID SCIENCE AND TECHNOLOGY 122 2 2019年10月21日 [査読有り][通常論文]
   

  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.
• Examination of the Catabolic Rates of 13C-Labeled Fatty Acids Bound to the α and β Positions of Triacylglycerol Using 13CO2 Expired from Mice.

  Kazuaki Yoshinaga, Fumiaki Beppu, Yoshio Yamatani, Atsushi Kubo, Aya Yoshinaga-Kiriake, Toshiharu Nagai, Akihiko Yoshida, Jota Kanda, Naohiro Gotoh

  Journal of oleo science 68 6 591 - 598 2019年06月06日 [査読有り][通常論文]
   

  Fatty acids in triacylglycerol (TAG) are catabolized after digestion. However, the catabolic rates of several fatty acids bound to the α (sn-1, 3) or β (sn-2) position of TAG have not been thoroughly compared. In this study, the catabolic rates of 13C-labeled palmitic acid, oleic acid, linoleic acid, α-linolenic acid, eicosapentaenoic acid (EPA), or docosahexaenoic acid (DHA) bound to the α and β position of TAG were compared using isotope ratio mass spectrometry. The catabolic rates of the studied fatty acids were evaluated using the ratio of 13C and 12C in carbon dioxide expired from mice. The results indicated that palmitic acid, oleic acid, or α-linolenic acid bound to the β position was slowly catabolized for a long duration compared to that when bound to the α position. In contrast, EPA bound to the β position was quickly catabolized, and EPA bound to the α position was slowly catabolized for a long time. For linoleic acid or DHA, no difference in the catabolic rates was detected between the binding positions in TAG. Furthermore, EPA and DHA were less catabolized than the other fatty acids. These results indicate that the catabolic rates of fatty acids are influenced by their binding positions in TAG and that this influence on the catabolic rate differed depending on the fatty acid species.
• Comparison of the Effects of Long-chain Monounsaturated Fatty Acid Positional Isomers on Lipid Metabolism in 3T3-L1 Cells.

  Samanthika Senarath, Fumiaki Beppu, Kazuaki Yoshinaga, Toshiharu Nagai, Akihiko Yoshida, Naohiro Gotoh

  Journal of oleo science 68 4 379 - 387 2019年04月01日 [査読有り][通常論文]
   

  Long chain monounsaturated fatty acids (LC-MUFAs) have shown beneficial health effects in previous studies. They occur as mixtures of positional isomers (PIs) in food. The functionalities of LC-MUFA PIs have not been studied extensively. Common LC-MUFA PIs, namely cis-octadecenoic acid (c-18:1), cis-eicosenoic acid (c-20:1), and cis-docosenoic acid (c-22:1), were screened based on their effects on lipid accumulation. We selected nine fatty acids (FAs) to assess their effects on cellular lipid metabolism using 3T3-L1 preadipocytes. Lipid accumulation was found to be higher in cells treated with LC-MUFAs than in the non-treated cells. When comparing the influence of chain length of LC-MUFAs, TG levels tended to be higher in cells treated with c-22:1 group than that of the c18:1 and c-20:1 groups. Among the c-22:1 group, c9-22:1 treatment showed higher lipid accumulation, and was accompanied with elevated expression of transcription factors related to adipogenesis and lipogenesis, such as PPARγ and C/EBPα, and SREBP-1, respectively. In contrast, the effects of c-20:1 FAs were less pronounced than those of c-18:1 and c-22:1. Levels of accumulated lipid in cells treated with c15-20:1 were the same as in non-treated control. PPARγ, C/EBPα, and SREBP-1 were expressed at lower levels with c15-20:1 FA. Furthermore, mRNA levels of SCD-1 and FAS were lowered more by c15- and c11-20:1 than by other MUFAs. These results revealed that differences in the effects of LC-MUFAs on lipid metabolism depend on their chain lengths and on the position of the double bond.
• Evaluating the Content and Distribution of Trans Fatty Acid Isomers in Foods Consumed in Japan.

  Naohiro Gotoh, Kazuaki Yoshinaga, Satoshi Kagiono, Yukiko Katoh, Yota Mizuno, Fumiaki Beppu, Toshiharu Nagai, Hoyo Mizobe, Akihiko Yoshida, Koji Nagao

  Journal of oleo science 68 2 193 - 202 2019年02月01日 [査読有り][通常論文]
   

  Trans fatty acids (TFA) are considered risk factors for cardiovascular disease. However, detailed information on total content of TFA and TFA isomers and distribution of trans-octadecenoic acid positional isomers in foods consumed in Japan is not available till date. In this study, 250 foods, 169 processed foods and 81 foods derived from ruminant meat or milk, were analyzed. According to the results, most foods contained less than 1.0 g TFA / 100 g food. However, almost all foods containing butter had more than 1.0 g TFA / 100 g food. TFA isomers in foods were classified into two categories, monoene-rich type and polyenerich type. We hypothesized that these differences were attributed to diverse TFA formation mechanisms. Furthermore, we observed that trans-10-18:1 was also the dominant trans-18:1 positional isomer in foods consumed in Japan. These results are valuable for future analysis of the role of TFA in epidemiological studies in Japan.
• Effect of calcium treatment on catabolic rates of 13C-labeled fatty acids bound to the α and β positions of triacylglycerol.

  K. Yoshinaga, F. Beppu, Y Yamatani, A. Kubo, A. Yoshinaga-Kiriake, T. Nagai, A. Yoshida, J. Kanda, N. Gotoh

  J. Oleo Sci. in press 11 1149 - 1155 2019年 [査読有り][通常論文]
   

  The absorption efficacies and catabolic rates of fatty acids are affected by their binding position on triacylglycerol (TAG). However, the kind of effect calcium treatment has on the catabolism of fatty acids is unclear. In this study, the catabolic rates of 13C-labeled palmitic acid, oleic acid, and linoleic acid bound to sn-1, 3 (α) and sn-2 (β) position of TAG in the presence of calcium were compared using isotope ratio mass spectrometry. The catabolic rates of 13C-labeled fatty acids were evaluated using the ratio of 13C to 12C in the carbon dioxide expired by mice. The catabolic rate of palmitic acid bound to the α position was significantly lower than that of palmitic acid bound to the β position of TAG. The rates of 13CO2 formation from palmitic acid at the β position remained higher for a long time. In contrast, oleic and linoleic acids at the α position were as well catabolized as those at the β position. These results indicate that in the presence of calcium, the saturated fatty acid bound to the β position is highly catabolized, whereas that bound to the α position is not well catabolized. Saturated fatty acid at the α position is hydrolyzed by pancreatic lipase to promptly form insoluble complexes with calcium, which are excreted from the body, and thereby reducing the catabolic rate of these fatty acids.
• Metabolism of Natural Highly Unsaturated Fatty Acid, Tetracosahexaenoic Acid (24:6n-3), in C57BL/KsJ-db/db Mice.

  Naohiro Gotoh, Koji Nagao, Hiroki Ishida, Kazusa Nakamitsu, Kazuaki Yoshinaga, Toshiharu Nagai, Fumiaki Beppu, Aya Yoshinaga-Kiriake, Hiroyuki Watanabe, Teruyoshi Yanagita

  Journal of oleo science 67 12 1597 - 1607 2018年12月01日 [査読有り][通常論文]
   

  Tetracosahexaenoic acid (THA; 24:6n-3) is a natural, n-3 highly unsaturated fatty acid (n-3HUFA) that exists in fish, including Baltic herring (Clupea harengus) and the flathead flounder (Hippoglossoides dubius). In this study, natural n-3HUFAs, i.d. eicosapentaenoic acid (EPA, 20:5n-3), docosahexaenoic acid (DHA, 22:6n-3), and THA were administrated to C57BL/KsJ-db/db mice for 4 weeks and the liver and serum lipid profiles, hepatic enzyme activity, expression of mRNA related to lipid metabolism, and adiponectin serum levels were then analyzed. The results showed that THA had the highest activity in suppressing hepatic triglyceride (TG) accumulation and increase in liver weight among the test groups. Furthermore, THA increased adiponectin levels in serum. These results indicate that THA is an excellent natural n-3HUFA that can suppress the development of metabolic syndromes and circulatory system diseases. The order of the n-3HUFA activity was THA > DHA > EPA in almost all the factors examined here. In a previous study of ours, the order was DHA > DPA > EPA, so the final order was summarized as THA > DHA > DPA > EPA. This order clearly translates to the rule that "the number of double bonds and carbon atoms in the n-3HUFA structure relates to their clinical functions".
• Simple Quantification of Lactones in Milk Fat by Solvent Extraction Using Gas Chromatography-Mass Spectrometry.

  Junji Obi, Kazuaki Yoshinaga, Arisa Tago, Toshiharu Nagai, Akihiko Yoshida, Fumiaki Beppu, Naohiro Gotoh

  Journal of oleo science 67 8 941 - 948 2018年08月01日 [査読有り][通常論文]
   

  The analysis of lactones as an indicator of milk quality is important in food manufacturing. However, the extraction of lactones requires sensitive conditions due to their volatility. In this study, the parameters for resolution of lactone standards were evaluated by gas chromatography-electron ionization/mass spectrometry (GC-EI/MS) to develop a rapid and simple method for the quantification and compositional analysis of lactones in edible fats, especially milk fat. Fourteen lactone standards consisting of 6-16 carbon atoms were analyzed and their correction factors (CFs) were obtained by using δ-undecalactone as an internal standard. The CFs of the lactone standards followed the same trend for δ-lactones and γ-lactones. Three volume equivalents of organic solvent per unit sample yielded the best recovery in the lactone analysis. Notably, 91-114% lactone recovery for the standards was achieved with methanol as the extractant. This method was also applicable to other fat samples, such as virgin coconut oil that is thought to contain large amounts of lactones. The recovery of lactones from virgin coconut oil was in the range of 87-104%, indicating that the developed method is also applicable to solid or semi-solid fat samples. The lactone content of butter oil, coconut oil, and butter samples was calculated by using the obtained CFs and the results were in good agreement with those of previous reports. Consequently, the GC-EI/MS method developed in this study is deemed applicable for the quantification of lactones in fat samples.
• Differential Effect of cis-Eicosenoic Acid Positional Isomers on Adipogenesis and Lipid Accumulation in 3T3-L1 Cells

  Samanthika Senarath, Kazuaki Yoshinaga, Toshiharu Nagai, Akihiko Yoshida, Fumiaki Beppu, Naohiro Gotoh

  European Journal of Lipid Science and Technology 120 6 2018年06月 [査読有り][通常論文]
   

  © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Cis-eicosenoic acid-rich fish oil have shown beneficial health effects toward obesity-related metabolic dysfunctions. Six bioavailable cis-eicosenoic acid positional isomers (c-20:1 PIs) are examined for their effects on adipogenesis and lipid accumulation using 3T3-L1 preadipocytes. Cells are cultured using experimental (c-20:1 PIs-added, 50 µM) or control (oleic acid (c9-18:1, 50 µM) or no fatty acids) medium. The treatment of c-20:1 PIs, significantly (p < 0.05) decreases the cellular triglyceride content compared to that of c9-18:1. Cells absorbed c-20:1 PIs at significantly (p < 0.05) different percentages and has altered the fatty acid metabolism. The c15-20:1 comparatively down-regulated the transcriptional factors for adipogenesis (peroxisome proliferative-activated receptor gamma and CCCAT enhancer binding protein alpha) and lipogenesis (sterol regulatory element binding protein-1); thus, show comparative anti-adipogenic and anti-lipogenic effect. In conclusion, c-20:1 PIs affect differently on adipogenesis and lipid accumulation in 3T3-L1 cells and the position of the double bond in c-20:1 influences on their functionality. Practical applications: The control of the adipogenesis and lipid accumulation in adipocytes via improving the composition of dietary fat is useful as a prevention measure for obesity and subsequent diseases. This study demonstrates the beneficial effect of cis-eicosenoic acid (c-20:1) positional isomers particularly c15-20:1 in controlling the adipogenesis and subsequent lipid accumulation in adipocytes. Thus, food rich in 20:1 positional isomers, such as fish oil, plant seeds, and nuts are useful as functional foods for the prevention of obesity and could also use as effective weight loss supplements. The effect of cis-eicosenoic acid positional isomers (c-20:1 PIs) on the adipogenesis and lipid accumulation is studied using 3T3-L1 preadipocytes. Cells are cultured using experimental (c-20:1 PIs-added, 50 μM) or control (oleic acid (c9-18:1, 50 μM) or no fatty acids) medium. The treatment of c-20:1 PIs, particularly c15-20:1 significantly (p < 0.05) decreases the cellular triglyceride content compared to that of c9-18:1 and subsequently reduces the lipid accumulation in cells.
• Study of Trans Fatty Acid Formation in Oil by Heating Using Model Compounds.

  Naohiro Gotoh, Satoshi Kagiono, Kazuaki Yoshinaga, Hoyo Mizobe, Toshiharu Nagai, Akihiko Yoshida, Fumiaki Beppu, Koji Nagao

  Journal of oleo science 67 3 273 - 281 2018年03月01日 [査読有り][通常論文]
   

  The intake of trans fatty acids (TFAs) in foods changes the ratio of low density lipoprotein (LDL) to high density lipoprotein (HDL) cholesterol in blood, which causes cardiovascular disease. TFAs are formed by trans isomerization of unsaturated fatty acids (UFAs). The most recognized formation mechanisms of TFAs are hydrogenation of liquid oil to form partially hydrogenated oil (PHO,) and biohydrogenation of UFAs to form TFA in ruminants. Heating oil also forms TFAs; however, the mechanism of formation, and the TFA isomers formed have not been well investigated. In this study, the trans isomerization mechanism of unsaturated fatty acid formation by heating was examined using the model compounds oleic acid, trioleate, linoleic acid, and trilinoleate for liquid plant oil. The formation of TFAs was found to be suppressed by the addition of an antioxidant and argon gas. Furthermore, the quantity of formed TFAs correlated with the quantity of formed polymer in trioleate heated with air and oxygen. These results suggest that radical reactions form TFAs from UFAs by heating. Furthermore, trans isomerization by heating oleic acid and linoleic acid did not change the original double bond positions. Therefore, the distribution of TFA isomers formed was very simple. In contrast, the mixtures of TFA isomers formed from PHO and ruminant UFAs are complicated because migration of double bonds occurs during hydrogenation and biohydrogenation. These findings suggest that trans isomerization by heating is executed by a completely different mechanism than in hydrogenation and biohydrogenation.
• Quantitative analysis of the accumulation of marine-derived tocopherol in the tissue of mice fed with salmon roe oil using HPLC-fluorescence

  Fumiaki Beppu, Hitomi Kondo, Satoshi Kasatani, Yoshinori Aoki, Naohiro Gotoh

  Journal of Oleo Science 67 3 283 - 288 2018年 [査読有り][通常論文]
   

  In this study, we measured the quantity of marine-derived tocopherol (MDT), a monounsaturated vitamin E (VE), stored in the body tissue of mice fed with a diet containing a VE-rich fraction extracted from salmon roe. We first prepared the calibration curves for the MDT concentration using an HPLC-fluorescence system. Ranging from 0.016 to 50 μg/mL, the slope was expressed as first-order equations, with R2 values = 0.99. The mice were fed with an AIN-93 based diet containing MDT in doses of 21.4 mg/kg for 4 weeks, and the storage in the heart, lung, liver, stomach, small intestine, large intestine, kidney, pancreas, spleen, testis, skeletal muscle, visceral white adipose tissue (WAT), subcutaneous WAT and brain was quantified. MDT was widely distributed in tissues throughout the whole body, with higher accumulations observed in the adipose tissue, liver and kidney. These results demonstrate means to estimating the MDT concentration in natural products and in the bodies of animals and contribute to the understanding of the physiological functions of MDT in relation to human health.
• Homochiral Asymmetric Triacylglycerol Isomers in Egg Yolk

  Toshiharu Nagar, Keiko Ishikawa, Kazuaki Yoshinagal, Akihiko Yoshida, Fumiaki Beppu, Naohiro Gotoh

  JOURNAL OF OLEO SCIENCE 66 12 1293 - 1299 2017年12月 [査読有り][通常論文]
   

  The composition of triacylglycerol (TAG) positional isomer (-PI) and enantiomer (-E) in immature chicken egg yolk, mature chicken yolk, and chicken meat was examined. POO (consisting of one palmitic acid (P) and two oleic acids (Os)), PPO (consisting of two Ps and one O), and PPL (consisting of two Ps and one linoleic acid (L)) were treated as representative TAG molecular species in all the analytical samples because P, O, and L were the major fatty acids comprising egg and chicken meat. sn-POO (binding P at sn-1 position) was predominant in egg yolks, while sn-OOP and sn-OPO were present in chicken meat. This difference was ascribed to the different roles of these isomers as nutrients, because TAG in egg yolk is important for new born organisms and TAG in chicken meat is used for fat accumulation. The compositions of the TAG isomers in PPO and PPL in egg yolk were similar, and O and L did not bind at the sn-1 position. In contrast, all the isomers of PPO and PPL were found in chicken meat. These results imply that the TAG structure could be modified so that the nutrient requirement is fulfilled in egg yolk and chicken meat.
• Quantification of Fraglide-1, a New Functional Ingredient, in Vinegars

  Aydan H. Yatmazt, Tetsuaki Kinoshita, Akio Miyazato, Masahiro Takagi, Yoshio Tsujino, Fumiaki Beppu, Naohiro Gotoh

  JOURNAL OF OLEO SCIENCE 66 12 1381 - 1386 2017年12月 [査読有り][通常論文]
   

  Vinegar is a widely used condiment in the world, and is produced from ethanol by acetic acid fermentation. Different fruits, vegetables, cereals, and wines can be used as ingredients for vinegar production. It is known that vinegar has many nutrient components such as organic acids, polyphenols, and aromatic compounds. Because of these bioactive components, it has many health benefits. China has a long history of producing vinegar and has been using it for health products and as medicine. Chinese aromatic Zhenjiang vinegar (Kozu) is produced from sticky rice. It is famous for its special flavor and health benefits. 5-Hydroxy-4-phenyl-butenolide (Fraglide-1) is a functional compound discovered in Kozu and has anti fungal and anti-obesity effects. In this study, the Fraglide-1 content of different kinds of vinegars and ingredients, including Kozu samples and ingredients, was investigated. Fraglide-1 analysis was carried out via LC-MS/MS in multiple reaction monitoring mode. It was found that all the Kozu samples, as well as brown rice vinegar (Kurosu) samples, and the Chinese sticky rice husk used for the production of Kozu, contained Fraglide-1. Kozu production requires a 6-month- to 8-year-long aging process for its special flavor and aroma. Because of this long aging process, Fraglide-1 is thought to move from the sticky rice husk to Kozu.
• Comparison of the Distribution of Unsaturated Fatty Acids at the Sn-2 Position of Phospholipids and Triacylglycerols in Marine Fishes and Mammals

  Fumiaki Beppu, Keiko Yasuda, Ayako Okada, Yoshitsugu Hirosaki, Masako Okazaki, Naohiro Gotoh

  JOURNAL OF OLEO SCIENCE 66 11 1217 - 1227 2017年11月 [査読有り][通常論文]
   

  Highly unsaturated fatty acid (HUFA) binding at the sn-2 position of phospholipids (PL) becomes a resource for prostaglandin, leukotriene, resolvin, and protectin synthesis. Both triacylglycerol (TAG) and PL synthesis pathways in vivo are via phosphatidic acid; therefore, the distribution of fatty acid species at the sn-2 position must theoretically be the same for TAG and PL if rearrangement does not occur. However, it is known that little HUFA is located at the sn-2 position of TAG in marine mammals. Therefore, distribution of fatty acid species at the sn-2 position of TAG and PL was compared between marine fishes and mammals in this study. The composition of fatty acids binding at the sn-2 or sn-1,3 position of PL and TAG was analyzed via hydrolysis with enzymes and GC-FID. The results showed that 20:4n-6, 20:5n-3, 22:5n-3, and 22:6n-3 were primarily located at the sn-1,3 positions of TAG in marine mammals. Comparison of the binding positions of HUFA and 16:0 in PL and TAG suggested the existence of Lands' cycle in marine fishes and mammals. In conclusion, both marine fishes and mammals condensed HUFA as a source of eicosanoid at the sn-2 position of PL. Furthermore, abundance ratios for 22:5n-3 or 22:6n-3 at the sn-2 position (sn-2 ratio) in TAG and PL (calculated by the equation: [abundance ratio at sn-2 position of TAG]/[abundance ratio at sn-2 position of FL]) was less than 0.35 in marine mammals; however, it was greater than 0.80 in marine fishes. These differences suggested that the HUFA consisted of 22 carbon atoms and had different roles in marine fishes and mammals.
• Comparison of the Effect of trans Fatty Acid Isomers on Apolipoprotein A1 and B Secretion in HepG2 Cells

  Koji Nagao, Kazuaki Yoshinaga, Toshiharu Nagai, Hoyo Mizobe, Akihiko Yoshida, Fumiaki Beppu, Naohiro Gotoh

  JOURNAL OF OLEO SCIENCE 66 10 1175 - 1181 2017年10月 [査読有り][通常論文]
   

  Intake of trans fatty acid (TFA) is believed to change the ratio of low-density lipoprotein (LDL) to high density lipoprotein (HDL) cholesterol in blood, which leads to cardiovascular disease. In this study, thirteen types of TFA including monoene type TFA (trans-octadecenoic fatty acid isomers, t-18:1 isomers), diene type TFA (t9412-18:2), and triene type TFA (t-18:3) were added to cultured HepG2 cells to compare the amount of apolipoprotein A1 and B (those relating to levels of HDL and LDL cholesterol in blood, respectively) being secreted. We found that trans-5-18:1 increased the secretion of apolipoprotein B relative to oleic acid (cis-9-18:1, control). Secretion of apolipoprotein B was also increased by t-18:3; however, the amount was not significant compared with that observed in the control. The secretion amount of apolipoprotein B tended to increase with the number of double bonds in TFA among trans-9-18:1, t9,t1218:2, and t-18:3. The secretion amount of apolipoprotein Al after TFA treatment was also measured. No significant difference was detected among t-18:1 groups; however, t-18:3 increased the amount significantly compared to that in the control. These results suggest that the effect of TFA isomers on the ratio of LDL to HDL cholesterol in the blood follows a mechanism different from that in cultured cells.
• Dietary Starfish Oil Prevents Hepatic Steatosis and Hyperlipidemia in C57BLI6N Mice Fed High-fat Diet

  Fumiaki Beppu, Haoqi Li, Kazuaki Yoshinaga, Toshiharu Nagai, Akihiko Yoshinda, Atsushi Kubo, Jota Kanda, Naohiro Gotoh

  JOURNAL OF OLEO SCIENCE 66 7 761 - 769 2017年07月 [査読有り][通常論文]
   

  Starfish oil (SO) is characterized by functional lipids, including n-3 polyunsaturated fatty acid (both in the form of triacylglycerol and in the form of phospholipid), and carotenoids, which may exert beneficial effects on metabolic disorders in obesity-associated diseases. In the present study, the effect of SO on dysregulation of lipid metabolism was examined using C57BL/6N mice treated with high-fat (HF) diet. Mice were fed HF, HF with 2% SO, or HF with 5% SO diet for 8 weeks. Weight gain, blood glucose, serum and hepatic lipid contents, and hepatic fatty acid composition were measured. Fatty acid (3-oxidation activity was monitored by measuring the catabolic rate of C-13-labeled fatty acid, assessed as (CO2)-C-13/(CO2)-C-12 ratio using isotope ratio mass spectrometry (IR-MS). Although there were no differences in body weight or white adipose tissue weight among the test groups, dietary SO reduced blood glucose, and dose-dependently improved hyperlipidemia and decreased hepatic lipid accumulation. Analysis of hepatic fatty acid composition revealed a significant decrease in the ratio of monounsaturated fatty acid to saturated fatty acid, which is attributed to stearoyl-CoA desaturase activity. IR-MS analysis suggested that (3-oxidation activity was enhanced in the mice treated with 5% SO. These results demonstrate that dietary SO improves lipid metabolism measures in HF diet-induced obese mice, suggesting that SO holds promise as an agent for the prevention and treatment of lipid metabolism disorders in the liver.
• Acute Effect of Metformin on Postprandial Hypertriglyceridemia through Delayed Gastric Emptying

  Daisuke Sato, Katsutaro Morino, Fumiyuki Nakagawa, Koichiro Murata, Osamu Sekine, Fumiaki Beppu, Naohiro Gotoh, Satoshi Ugi, Hiroshi Maegawa

  INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 18 6 2017年06月 [査読有り][通常論文]
   

  Postprandial hypertriglyceridemia is a potential target for cardiovascular disease prevention in patients with diabetic dyslipidemia. Metformin has been reported to reduce plasma triglyceride concentrations in the postprandial states. However, little is known about the mechanisms underlying the triglyceride-lowering effect of metformin. Here, we examined the effects of metformin on lipid metabolism after olive oil-loading in 129S mice fed a high fat diet for three weeks. Metformin administration (250 mg/kg) for one week decreased postprandial plasma triglycerides. Pre-administration (250 mg/kg) of metformin resulted in a stronger triglyceride-lowering effect (approximately 45% lower area under the curve) than post-administration. A single administration (250 mg/kg) of metformin lowered plasma postprandial triglycerides comparably to administration for one week, suggesting an acute effect of metformin on postprandial hypertriglyceridemia. To explore whole body lipid metabolism after fat-loading, stomach size, fat absorption in the intestine, and fat oxidation (C-13/C-12 ratio in expired CO2 after administration of glyceryl-1-C-13 tripalmitate) were measured with and without metformin (250 mg/kg) pre-treatment. In metformin-treated mice, larger stomach size, lower fat oxidation, and no change in lipid absorption were observed. In conclusion, metformin administration before fat loading reduced postprandial hypertriglyceridemia, most likely by delaying gastric emptying.
• Quantification of Triacylglycerol Molecular Species in Edible Fats and Oils by Gas Chromatography-Flame Ionization Detector Using Correction Factors

  Kazuaki Yoshinaga, Junji Obi, Toshiharu Nagai, Hiroyuki Iioka, Akihiko Yoshida, Fumiaki Beppu, Naohiro Gotoh

  JOURNAL OF OLEO SCIENCE 66 3 259 - 268 2017年03月 [査読有り][通常論文]
   

  In the present study, the resolution parameters and correction factors (CFs) of triacylglycerol (TAG) standards were estimated by gas chromatography-flame ionization detector (GC-FID) to achieve the precise quantification of the TAG composition in edible fats and oils. Forty seven TAG standards comprising capric acid, lauric acid, myristic acid, pentadecanoic acid, palmitic acid, palmitoleic acid, stearic acid, oleic acid, linoleic acid, and/or linolenic acid were analyzed, and the CFs of these TAGs were obtained against tripentadecanoyl glycerol as the internal standard. The capillary column was Ultra ALLOY(+)-65 (30 m x 0.25 mm i.d., 0.10 gm thickness) and the column temperature was programmed to rise from 250 degrees C to 360 degrees C at 4 degrees C/min and then hold for 25 min. The limit of detection (LOD) and limit of quantification (LOQ) values of the TAG standards were > 0.10 mg and > 0.32 mg per 100 mg fat and oil, respectively, except for LnLnLn, and the LOD and LOQ values of LnLnLn were 0.55 mg and 1.84 mg per 100 mg fat and oil, respectively. The CFs of TAG standards decreased with increasing total acyl carbon number and degree of desaturation of TAG molecules. Also, there were no remarkable differences in the CFs between TAG positional isomers such as 1-palmitoyl-2-oleoyl-3-stearoyl-rac-glycerol, 1-stearoyl-2-palmitoyl-3-oleoyl-rac-glycerol, and 1-palmitoyl-2-stearoyl-3-oleoyl-rac-glycerol, which cannot be separated by GC-FID. Furthermore, this method was able to predict the CFs of heterogeneous (AAB- and ABC-type) TAGs from the CFs of homogenous (AAA-, BBB-, and CCC-type) TAGs. In addition, the TAG composition in cocoa butter, palm oil, and canola oil was determined using CFs, and the results were found to be in good agreement with those reported in the literature. Therefore, the GC-FID method using CFs can be successfully used for the quantification of TAG molecular species in natural fats and oils.
• Quantitative Analysis of the Distribution of cis-Eicosenoic Acid Positional Isomers in Marine Fishes from the Indian Ocean

  Samanthika Senarath, Kazuaki Yoshinaga, Toshiharu Nagai, Akihiko Yoshida, Fumiaki Beppu, Chamila Jayasinghe, Chandravathany Devadawson, Naohiro Gotoh

  JOURNAL OF OLEO SCIENCE 66 2 187 - 197 2017年02月 [査読有り][通常論文]
   

  This study investigated the occurrence and distribution of cis-eicosenoic acid (c-20:1) positional isomers in fishes from the Indian Ocean and compared to those from the Pacific and Atlantic Ocean. Lipids were extracted from the edible part of the fish and then methylated. The eicosenoic acid methyl ester fraction was separated from total fatty acid methyl esters by reversed-phase HPLC and quantitatively analyzed using a GC-FID fitted with the SLB-IL111 highly polar GC column. c14-20:1 was used as an internal standard. The results indicated that the highest levels of c-20:1 positional isomers were found in fishes from the Pacific Ocean (saury, 166.95 +/- 12.4 mg/g of oil), followed by the Atlantic Ocean (capelin, 162.7 +/- 3.5 mg/g of oil), and lastly in fishes from the Indian Ocean (goatfish, 34.39 mg/g of oil). With only a few exceptions, the most abundant 20:1 positional isomer found in fishes of the Indian and Atlantic Ocean was the c11-20:1 isomer (>50%) followed by the c13-20:1 isomer (<25%). Unusually, the c7-20:1 isomer was predominantly found in a few fishes such as the tooth ponyfish, longface emperor, and commerson's sole. The c9, c5, and c15-20:1 isomers were the least occurring in fishes from the Indian and Atlantic Ocean. In contrast, the c9-20:1 isomer was the principal isomer identified in fishes from the Pacific Ocean. The results revealed that the content and distribution of c-20:1 positional isomers varied among fishes in different oceans. The data presented in the current study are the first to report on the distribution of c-20:1 positional isomers in fishes from the Indian Ocean.
• Comparison of 13C-labeled fatty acid catabolic rates bound to the sn-1, sn-2, and sn-3 positions of triacylglycerol using 13C-labeled CO2 expired from mice.

  F. Beppu, T. Kawamatsu, Y. Yamatani, T. Nagai, K. Yoshinaga, H. Mizobe, A. Yoshida, A. Kubo, J. Kanda, N. Gotoh

  J. Oleo Sci. 66 85 - 91 2017年 [査読有り][通常論文]
  
• Comparison of Catabolic Rates of sn-1, sn-2, and sn-3 Fatty Acids in Triacylglycerols Using (CO2)-C-13 Breath Test in Mice

  Fumiaki Beppu, Takashi Kawamatsu, Yoshio Yamatani, Toshiharu Nagai, Kazuaki Yoshinaga, Hoyo Mizobe, Akihiko Yoshida, Atsushi Kubo, Jota Kanda, Naohiro Gotoh

  JOURNAL OF OLEO SCIENCE 66 1 85 - 91 2017年01月 [査読有り][通常論文]
   

  Fatty acids in triacylglycerols (TAGs) are catabolized after digestion. However, the catabolic rates of the fatty acids at the sn-1, sn-2, and sn-3 positions of TAGs have not been compared. To elucidate the differences, we studied the catabolic rates of C-13-labeled palmitic acid, oleic acid, and capric acid at the sn-1, sn-2, or sn-3 position of TAGs using isotope-ratio mass spectrometry. Specifically, we measured the C-13-to-C-12 ratio in CO, (Delta C-13 (parts per thousand)) exhaled by mice. For all analyzed fatty acids, we observed significant differences between sn-2 and other binding positions. In contrast, no significant difference was detected between the sn-1 and sn-3 positions. These results indicated that the catabolic rates of fatty acids are strongly influenced by their positions in TAGs.
• Quantification of Triacylglycerol Positional Isomers in Rat Milk

  Natsuko Watanabe, Toshiharu Nagai, Hoyo Mizobe, Kazuaki Yoshinaga, Akihiko Yoshida, Yohei Kitamura, Takashi Shimizu, Fumiaki Beppu, Naohiro Gotohl

  JOURNAL OF OLEO SCIENCE 65 12 977 - 983 2016年12月 [査読有り][通常論文]
   

  The absolute amount of triacylglycerol (TAG) positional isomers was analyzed in rat milk fat, a representative of non-ruminant milk fat, using a HPLC-UV-atmospheric pressure chemical ionization-MS/MS system equipped with an octacosyl silylation column or polymeric ODS column. TAGs consisting of two oleic acids (0) and one palmitic acid (P) were the most abundant. In particular, beta-OPO, a TAG binding P at the beta-position (sn-2) and two Os at the alpha-positions (sn-113), was prominent. The beta-OPO content decreased over time, while a TAG consisting of two Ps and one capric acid, a medium-chain fatty acid, increased. TAGs consisting of two Ps and one docosahexaenoic acid were present in small amounts and decreased with time. These results indicated that the recombination of fatty acids in TAGs in milk fat occurs in the mother, and is thought to depend on the infant's stage of growth, in response to their nutritional needs. It was also demonstrated that medium-chain fatty acids were mainly located at the alpha-position (sn-3), while Ps were mainly located at the beta-position (sn-2). Therefore, the combination and binding positions of fatty acids of TAG are considered very important in infant nutrition.
• Comparative Analysis of Lipid Content and Fatty Acid Composition of Commercially Important Fish and Shellfish from Sri Lanka and Japan

  Chandravathany Devadason, Chamila Jayasinghe, Ramiah Sivakanesan, Samanthika Senarath, Fumiaki Beppu, Naohiro Gotoh

  JOURNAL OF OLEO SCIENCE 65 7 543 - 556 2016年07月 [査読有り][通常論文]
   

  Sri Lanka is surrounded by the Indian Ocean, allowing plenty of fishes to be caught. Moreover, these fishes represent one of the undocumented fish resources in the world and their detailed lipid profiles have not been previously examined. In this study, the lipid content and fatty acid composition of 50 commercially important fishes from the Indian Ocean (Sri Lanka) and the Pacific Ocean (Japan) were compared. The total lipid content and fatty acid composition, including eicosapentaenoic acid (C20:5n-3, EPA) and docosahexaenoic acid (C22:6n-3, DHA), differed significantly among species. Fish from the Pacific Ocean had higher proportions of fatty acids, including EPA and DHA. Herrings and mackerels from both oceanic areas demonstrated high levels of EPA and DHA, and n-3/n-6 ratio. Brackish and freshwater fishes from both groups showed low levels of PUFAs. Fish from the Indian Ocean were high in n-6 fatty acids. Monounsaturated fatty acid levels were high in omnivorous fish from the Pacific Ocean, and saturated fatty acid levels were high in fish from the Indian Ocean. The results of this study will be of value in determining the dietary usefulness of fish caught in Sri Lanka.
• Trans-octadecenoic Acid Positional Isomers Have Different Accumulation and Catabolism Properties in Mice

  Fumiaki Beppu, Masaharu Asanuma, Yoshinori Kawamura, Toshiharu Nagai, Kazuaki Yoshinaga, Hoyo Mizobe, Koichi Kojima, Satoshi Kasatani, Koji Nagao, Atsushi Kubo, Jota Kanda, Naohiro Gotoh

  JOURNAL OF OLEO SCIENCE 64 11 1159 - 1167 2015年11月 [査読有り][通常論文]
   

  Trans fatty acids (TFA) are considered risk factors for cardiovascular disease (CVD), while the details of distribution and metabolism of the individual isomers are not clear. Here we investigated the accumulation and catabolic rate of TFA positional isomers of octadecenoic acid (18:1) in mice. ICR mice were fed deuterium- and [1-C-13] stable isotope-labeled trans-9-18:1 (9t-18:1(star)), trans-10-18:1 (10t-18:1(star)), or trans-11-18:1 (11t-18:1(star)) for 2 or 4 weeks, or a TFA mixture (9t-18:1(star), 10t-18:1(star), and 11t-18:1(star)) for 3 weeks. Analysis of whole-body tissues by gas chromatography-chemical ionization mass spectrometry revealed the highest 9t-18:1(star) levels in the heart. Significant differences in the accumulation of the respective trans-18:1 were observed in the heart and erythrocytes, where 9t- > 11t- > 10t-18:1(star), but no significant difference was observed in the liver or white adipose tissue (WAT). Mice fed on 11t-18:1 demonstrated accumulation of endogenously synthesized conjugated linoleic acid in the liver, WAT, and heart, but any other metabolites were not found in other groups. Furthermore, we analyzed catabolic rates of single-dose-administered trans-18:1(star) isomers into [C-13]-labeled CO2 using isotope-ratio mass spectrometry, and the 10t-18:1*catabolic rate was significantly higher than those of 9t- and 11t-18:1(star). We found that the accumulation and catabolism of trans-18:1 positional isomers varied in these mice. Differential accumulation in tissues suggests that individual TFA positional isomers may play different roles in human health.
• Abundances of Triacylglycerol Positional Isomers and Enantiomers Comprised of a Dipalmitoylglycerol Backbone and Short- or Medium-chain Fatty Acids in Bovine Milk Fat

  Toshiharu Nagai, Natsuko Watanabe, Kazuaki Yoshinaga, Hoyo Mizobe, Koichi Kojima, Lkuma Kuroda, Yuki Odanaka, Tadao Saito, Fumiaki Beppu, Naohiro Gotoh

  JOURNAL OF OLEO SCIENCE 64 9 943 - 952 2015年09月 [査読有り][通常論文]
   

  Bovine milk fat (BMF) is composed of triacylglycerols (TAG) rich in palmitic acid (P), oleic acid (0), and short-chain or medium-chain fatty acids (SCFAs or MCFAs). The composition and binding positions of the fatty acids on the glycerol backbone determine their physical and nutritional properties. SCFAs and MCFAs are known to characteristically bind to the sn-3 position of the TAGs in BMF; however, there are very few non-destructive analyses of TAG enantiomers binding the fatty acids at this position. We previously reported a method to resolve the enantiomers of TAGs, binding both long-chain saturated fatty acid and unsaturated fatty acid at the sn-1 and 3 positions, in palm oil, fish oil, and marine mammal oil using chiral HPLC. Here, we further developed a method to resolve several TAG enantiomers containing a dipalmitoyl (PP) glycerol backbone and one SCFA (or MCFA) in BMF. We revealed that the predominant TAG structure in BMF was homochiral, such as 1,2-dipalmitoy1-3-butyroyl-sn-glycerol. This is the first quantitative determination of many TAG enantiomers, which bind to a SCFA or MCFA, in BMF was evaluated simultaneously. Furthermore, the results indicated that the amount ratios of the positional isomers and enantiomers of TAGs consisting of a dipalmitoyl (PP) glycerol backbone and SCFA (or MCFA), resembled the whole TAG structures containing the other diacylglycerol backbones consisting of P, 0, myristic acid, and/or stearic acid in BMF.
• Generation of Tetracosahexaenoic Acid in Benthic Marine Organisms

  Rei Suo, Haoqi Li, Kazuaki Yoshinaga, Toshiharu Nagai, Hoyo Mizobe, Koichi Kojima, Koji Nagao, Fumiaki Beppu, Naohiro Gotoh

  JOURNAL OF OLEO SCIENCE 64 7 721 - 727 2015年07月 [査読有り][通常論文]
   

  Tetracosahexaenoic acid (THA, 24:6n-3) has been shown to have the strongest ability to suppress accumulation of lipids in HepG2 cells among well-known n-3 highly unsaturated fatty acids, such as EPA and DHA. In this study, a method for mass production of THA was investigated using distributions of THA and DHA in thirty-two marine organisms, such as starfishes, right-eyed flounders, shellfishes, and sharks. The fatty acid composition of the marine organisms was analyzed using GC-FID and THA was detected in starfish, right-eyed flounder, and shark. Furthermore, the ratio of DHA and THA (DHA/THA) in each sample was calculated using chromatogram peak area of GC-FID, and the value was found to be lower than 1 in some starfishes. As a result, THA was thought to be synthesized in the starfishes. In contrast, the value of DHA/THA for right-eyed flounder and sharks was greater than 1. The THA accumulation in right-eyed flounder was considered to be because of the starfishes that the flounder consumes as part of its diet. DHA is synthesized from THA by beta-oxidation in peroxisomes, in the Sprecher's shunt. The high accumulation of THA observed in the flounder would be caused by the decreasing enzyme activation due to beta-oxidation in the peroxisomes of the starfishes. Understanding the differences in THA between aquatic species could also potentially allow us to understand why THA is generated in marine animals.
• Regiospecific Distribution of trans-Octadecenoic Acid Positional Isomers in Triacylglycerols of Partially Hydrogenated Vegetable Oil and Ruminant Fat

  Kazuaki Yoshinaga, Yoshinori Kawamura, Takashi Kitayama, Toshiharu Nagai, Hoyo Mizobe, Koichi Kojima, Yomi Watanabe, Shinichi Sato, Fumiaki Beppu, Naohiro Gotoh

  JOURNAL OF OLEO SCIENCE 64 6 617 - 624 2015年06月 [査読有り][通常論文]
   

  It is revealed that binding position of fatty acid in triacylglycerol (TAG) deeply relates to the expression of its function. Therefore, we investigated the binding positions of individual trans-octadecenoic acid (trans-C18:1) positional isomers, known as unhealthy fatty acids, on TAG in partially hydrogenated canola oil (PHCO), milk fat (MF), and beef tallow (BT). The analysis was carried out by the sn-1(3)-selective transesterification of Candida antarctica Lipase B and by using a highly polar ionic liquid capillary column for gas chromatography flame ionization detection. Trans-9-C18:1, the major trans-C18:1 positional isomer, was selectively located at the sn-2 position of TAG in PHCO, although considerable amounts of trans9-C18:1 were also esterified at the sn-1(3) position. Meanwhile, trans-11-C18:1, the major isomer in MF and BT, was preferentially located at the sn-1(3) position. These results revealed that the binding position of trans-C18:1 positional isomer varies between various fats and oils.
• Comparison of catabolic rates of C-13-labeled palmitic acid bound to the alpha and beta positions of triacylglycerol using CO2 expired from mice

  Fumiaki Beppu, Kaoru Konno, Takashi Kawamatsu, Toshiharu Nagai, Kazuaki Yoshinaga, Hoyo Mizobe, Koichi Kojima, Hiroyuki Watanabe, Naohiro Gotoh

  EUROPEAN JOURNAL OF LIPID SCIENCE AND TECHNOLOGY 117 5 718 - 723 2015年05月 [査読有り][通常論文]
   

  We investigated the catabolic rate of C-13-labeled palmitic acid (*P) bound to alpha (sn-1) or beta (sn-2) position of triacylglycerol (TAG) using isotope-ratio mass spectrometry. Specifically, we measured the C-13-to-C-12 ratio in CO2 expired from mice. After 30-75 min, *P bound to the alpha position was catabolized faster than that bound to the beta position. Thereafter, the catabolic rate of *P bound to the beta position increased and surpassed that bound to the alpha position. This indicated that binding position affected the catabolic rate of *P, possibly due to the different specificities of pancreatic lipase, lipoprotein lipase, and hepatic lipase. Next, we measured the catabolic rate of *P bound to TAG in combination with one of three unsaturated fatty acids (oleic acid, linoleic acid, or alpha-linolenic acid). When *P was bound to the beta position and Ln was bound to the alpha position, the catabolism of TAG was significantly higher than for other TAGs. This result suggests that fatty acid structure might affect the catabolism of counterpart fatty acids in TAG.
• Effects of Imidacloprid on Myogenesis in C2C12 Myoblasts

  Amanda Rutherford, Yoo Kim, Fumiaki Beppu, Yeonhwa Park

  FASEB JOURNAL 29 2015年04月 [査読有り][通常論文]
  
• Differential effects of triacylglycerol positional isomers containing n-3 series highly unsaturated fatty acids on lipid metabolism in C57BL/6J mice (vol 26, pg 57, 2015)

  Kazuaki Yoshinaga, Keiichi Sasaki, Hiroyuki Watanabe, Koji Nagao, Nao Inoue, Bungo Shirouchi, Teruyoshi Yanagita, Toshiharu Nagai, Hoyo Mizobe, Koichi Kojima, Fumiaki Beppu, Naohiro Gotoh

  JOURNAL OF NUTRITIONAL BIOCHEMISTRY 26 4 431 - 432 2015年04月 [査読有り][通常論文]
  
• Differential effects of triacylglycerol positional isomers containing n-3 series highly unsaturated fatty acids on lipid metabolism in C57BL/6J mice

  Kazuaki Yoshinaga, Keiichi Sasaki, Hiroyuki Watanabe, Koji Nagao, Nao Inoue, Bungo Shirouchi, Teruyoshi Yanagita, Toshiharu Nagai, Hoyo Mizobe, Koichi Kojima, Fumiaki Beppu, Naohiro Gotoh

  JOURNAL OF NUTRITIONAL BIOCHEMISTRY 26 1 57 - 63 2015年01月 [査読有り][通常論文]
   

  The present study investigated the effects of binding position of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) to triacylglycerol (TAG) on lipid metabolism in C5781/6J mice. Mice were treated with pure TAG positional isomers, including 1,2 (2,3)-dipalmitoy1-3(1)-eicosapentaenoyl glycerol, 1,3-dipalmitoy1-2-eicosapentaenoyl glycerol, 1,2(2,3)-dipalmitoy1-3(1)-docosahexaenoyl glycerol, and 1,3-dipalmitoy1-2-docosahexaenoyl glycerol. Compared to DHA bound to the a-position of TAG, DHA bound to the beta-position more effectively inhibited fatty acid synthetic enzymes and cholesterol-metabolism enzymes and thus reduced TAG and cholesterol concentrations in the serum and liver. EPA bound to the alpha-position of TAG, but not EPA bound to the beta-position of TAG, significantly decreased hepatic cholesterol concentrations. Additionally, EPA bound to the alpha-position of TAG increased the ratio of PGI(2) to TXA(2) to a higher degree than EPA bound to the beta-position. These results suggested that the binding position of EPA and DHA to TAG affected TAG and cholesterol metabolism as well as eicosanoid production in C57BL/6J mice. (C) 2015 Elsevier Inc. All rights reserved.
• Characterization of cis- and trans-octadecenoic acid positional isomers in edible fat and oil using gas chromatography-flame ionisation detector equipped with highly polar ionic liquid capillary column

  Kazuaki Yoshinaga, Masaharu Asanuma, Hoyo Mizobe, Koichi Kojima, Toshiharu Nagai, Fumiaki Beppu, Naohiro Gotoh

  FOOD CHEMISTRY 160 39 - 45 2014年10月 [査読有り][通常論文]
   

  In this study, the characterisation of all cis- and trans-octadecenoic acid (C18:1) positional isomers in partially hydrogenated vegetable oil (PHVO) and milk fat, which contain several cis- and trans-C18:1 positional isomers, was achieved by gas chromatography-flame ionisation detector equipped with a highly polar ionic liquid capillary column (SLB-IL111). Prior to analysis, the cis- and trans-C18:1 fractions in PHVO and milk fat were separated using a silver-ion cartridge. The resolution of all cis-C18:1 positional isomers was successfully accomplished at the optimal isothermal column temperature of 120 degrees C. Similarly, the positional isomers of trans-C18:1, except for trans-6-C18:1 and trans-7-C18:1, were separated at 120 degrees C. The resolution of trans-6-C18:1 and trans-7-C18:1 isomers was made possible by increasing the column temperature to 160 degrees C. This analytical method is suitable for determining the cis- and trans-C18:1 positional isomers in edible fats and oils. (C) 2014 Elsevier Ltd. All rights reserved.
• A Comparison of the Lipid-lowering Effects of Four Different n-3 Highly Unsaturated Fatty Acids in HepG2 Cells

  Koji Nagao, Kazusa Nakamitsu, Hiroki Ishida, Kazuaki Yoshinaga, Toshiharu Nagai, Hoyo Mizobe, Koichi Kojima, Teruyoshi Yanagita, Fumiaki Beppu, Naohiro Gotoh

  JOURNAL OF OLEO SCIENCE 63 10 979 - 985 2014年10月 [査読有り][通常論文]
   

  The effects on lipid metabolism of four different n-3 highly unsaturated fatty acids (n-3HUFA) including eicosapentaenoic acid (EPA, 20:5n-3), docosapentaenoic acid (DPA, 22:5n-3), docosahexaenoic acid (DHA, 22:6n-3), and tetracosahexaenoic acid (THA, 24:6n-3) were compared in the HepG2 cell model. None of the n-3HUFAs affected the viability of the cells. THA exerted the strongest suppression on the synthesis of triacylglycerol and cholesteryl ester (ChE), and the order of the strength of suppression was found to be THA > DHA > DPA > EPA. The mRNA level of fatty acid synthase was suppressed by the n-3HUFAs and the order of the strength of suppression by n-3HUFAs was the same in both triacylglycerol and ChE synthesis. These findings support previous animal test results using EPA, DPA, and DHA. In conclusion, both the number of carbon atoms and double bonds in an n-3HUFA structure has an effect on lipid metabolism in HepG2 cells.
• Resolution Behavior of cis- and trans-Octadecenoic Acid Isomers by AOCS Official Method Using SP-2560 Column

  Kazuaki Yoshinaga, Masaharu Asanuma, Chao Xu, Hoyo Mizobe, Koichi Kojima, Toshiharu Nagai, Fumiaki Beppu, Naohiro Gotoh

  JOURNAL OF OLEO SCIENCE 62 10 781 - 788 2013年10月 [査読有り][通常論文]
   

  The gas chromatography flame ionization detector equipped with a higher polarity column (i.e., SP-2560) has often been used for the quantification of trans-fatty acids in food. In particular, AOCS Ce 1h-05, the official method of the American Oil Chemists' Society (AOCS), is a highly effective method to separate the isomers of trans-fatty acids. In this study, the resolution behavior and the response factors of cis- and trans-octadecenoic acid methyl ester (C18:1-ME) isomers separated by the AOCS Ce 1h-05 method were investigated, and the contents of each cis- and trans-C18:1-ME isomer in partially hydrogenated vegetable oil (PHVO) and milk fat were quantified by using the calibration curves obtained for the respective isomers. The relative response factors for the trans- and cis-C18:1-ME isomers against the internal standard heneicosanoic acid methyl ester (C21:0-ME) were 1.031 +/- 0.040 (mean +/- SD) and 0.990 +/- 0.032, respectively. The relative response factors of trans-isomers tend to be higher than those of cis-C18:1-ME isomers. The peaks of cis-4-C18:1-ME, cis-5-C18:1-ME, cis-6-C18:1-ME, cis-7-C18:1-ME, cis-8-C18:1-ME, and cis-9-C18:1-ME isomers overlapped with those of trans-C18:1-ME isomers. Both PHVO and milk fat contained many types of cis- and trans-C18:1 isomers, and the total contents of the trans-C18:1 isomer in PHVO and milk fat were 28.01 g and 3.62 g per 100 g oil, respectively. When the trans-C18:1-ME isomer was separated from the cis-C18:1-ME by using a silver-ion cartridge column before the analyses, the total contents of the trans-C18:1 isomer in PHVO and milk fat were 23.03 g and 2.78 g per 100 g oil, respectively. The difference in the trans-C18:1 isomer content between the two methods was ascribed to the partial overlapping of cis-isomer peaks with the peaks of trans-C18:1-ME isomers, in the chromatogram.
• 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.
• Quantification of triacylglycerol molecular species in cocoa butter using high-performance liquid chromatography equipped with nano quantity analyte detector.

  Fumiaki Beppu, Toshiharu Nagai, Kazuaki Yoshinaga, Hoyo Mizobe, Koichi Kojima, Naohiro Gotoh

  Journal of oleo science 62 10 789 - 94 2013年 [査読有り][通常論文]
   

  Triacylglycerol (TAG) molecular species were quantified through high-performance liquid chromatography (HPLC) equipped with a nano quantity analyte detector (NQAD). TAG standard compounds, i.e., 1,3-dipalmitoyl-2-oleoylglycerol (β-POP), 1-palmitoyl-2-oleoyl-3-stearoyl-rac-glycerol (β-POS), and 1,3-distearoyl-2-oleoylglycerol (β-SOS), and natural cocoa butter were used for analyses. NQAD gave the first order equation passing through the origin for all TAG standard compounds. TAG molecular species in cocoa butter were quantified using the calibration curves and the obtained values were almost the same as the reported ones of conventional cocoa butter. Furthermore, a recovery test was also carried out and the values were almost 100. Therefore, HPLC-NQAD can be successfully used for the quantification of TAG molecular species in natural fats and oils.
• Actual ratios of triacylglycerol positional isomers and enantiomers comprising saturated fatty acids and highly unsaturated fatty acids in fishes and marine mammals.

  Toshiharu Nagai, Yumiko Matsumoto, Yanying Jiang, Keiko Ishikawa, Tokuhisa Wakatabe, Hoyo Mizobe, Kazuaki Yoshinaga, Koichi Kojima, Ikuma Kuroda, Tadao Saito, Fumiaki Beppu, Naohiro Gotoh

  Journal of oleo science 62 12 1009 - 15 2013年 [査読有り][通常論文]
   

  It has been previously shown that the positional isomers of triacylglycerol (TAG) containing palmitic acid (P) and highly unsaturated fatty acids (HUFAs) such as DHA (D) and EPA (E) vary between fishes and marine mammals. However, it has not yet been understood why in marine mammals HUFAs are located only at the α position when two palmitic acid chains combine, and not in fishes. In order to gain further understanding of the biosynthetic pathways involved in the formation of these asymmetric TAGs, we investigated whether the HUFA in the TAG of marine mammals exists predominantly at the sn-1 or sn-3 position. We examined the TAG positional isomers and enantiomers in marine organisms in detail. As a result, while PDP and PEP were not detected, sn-PPD and sn-PPE were found in abundance in marine mammals. For fishes, on the other hand, PDP, PEP, sn-PPD, and sn-PPE were all identified. In the case of TAGs that contain two HUFAs and one palmitic acid, marine mammals were rich in DPD and EPE whereas fishes were rich in sn-PDD and sn-PEE.
• 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 - 112 2012年09月10日 [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.
• 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]
  
• In Vivo and in Vitro Toxicity Studies of Fucoxanthin, a Marine Carotenoid

  Yoshimi Niwano, Fumiaki Beppu

  Handbook of Marine Macroalgae: Biotechnology and Applied Phycology 319 - 328 2011年11月21日 [査読有り][通常論文]
  
• 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
• 褐藻由来フコキサンチンによるstearoyl-CoA desaturase 1(SCD1)発現抑制効果

  篠田 太郎, 別府 史章, 津久井 隆行, 細川 雅史, 宮下 和夫

  日本栄養・食糧学会大会講演要旨集 65回 163 - 163 (公社)日本栄養・食糧学会 2011年04月
• 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.
• 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.
• 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.
• Hypolipidemic Effects of Ethanol Extracts of Citrus depressa and Annona atemoya, Typical Plant Foodstuffs in Okinawa, Japan on KKAy Mice Fed with Moderately High Fat Diet

  Fumiaki Beppu, Yoshimi Niwano, Rika Kyan, Kazumasa Yasura, Minori Tamaki, Michinori Nishino, Yoshiyuki Midorikawa, Hiroki Hamada

  FOOD SCIENCE AND TECHNOLOGY RESEARCH 15 5 553 - 556 2009年09月 [査読有り][通常論文]
   

  Okinawa is an isolated island prefecture of Japan and is known for the longest life expectancy and low disability rate. We therefore focused on the effects of traditional Okinawan fruits Citrus depressa and Annona atemoya consumed by the Okinawan population. Repeated oral administration of ethanol extracts of C depressa and A. atemoya potently lowered the plasma triglyceride (TG) concentrations of KKAy mice fed a moderately high fat diet for 4 weeks. Since diet intake and body weight were not reduced following administration of the C. depressa extract, TG absorption from the intestine is unlikely inhibited by this extract. Our previous study showed that the A. atemoya extract possesses a potent inhibitory effect on adipogenesis of 3T3 adipocytes. Thus, reduced fatty acid mobilization from the adipose tissue by the A. atemoya extract may result in the reduction in TG synthesis in the liver. This is the first report on the hypolipidemic effects of C. depressa and A. atemoya. Their extracts of these fruits are expected to be useful for the prevention of life style-related diseases.
• Extensive Screening for Plant Foodstuffs in Okinawa, Japan with Anti-Obese Activity on Adipocytes In Vitro

  Yoshimi Niwano, Fumiaki Beppu, Taichi Shimada, Rika Kyan, Kazumasa Yasura, Minori Tamaki, Michinori Nishino, Yoshiyuki Midorikawa, Hiroki Hamada

  PLANT FOODS FOR HUMAN NUTRITION 64 1 6 - 10 2009年03月 [査読有り][通常論文]
   

  To search for plant foodstuffs with potent anti-obese activity, we conducted a large scale screening based on the inhibitory activity on adipogenesis and the facilitating activity on adipolysis in vitro. That is, inhibition of intracellular lipid accumulation and facilitation of lipid degradation in 3T3-L1 adipocytes were extensively screened from ethanol and hexane extracts of approximately 100 kinds of plant foodstuffs marketed in Okinawa prefecture, which has been famous for the highest prevalence of exceptionally long-lived individuals in the world. Among them thirty one foodstuffs showed potent inhibitory activity on intracellular lipid accumulation in 3T3-L1 adipocytes, whereas only four foodstuffs showed clear facilitating effect on lipid degradation in 3T3-L1 adipocytes. Although further study to examine the in vivo effects on adipogenesis and adipolysis is required, this is the first study to investigate anti-obese characteristics of wide range of traditional Okinawa foodstuffs so that the results give useful information to take another look at Okinawa food culture.
• ナノマイザー技術を応用した全粒大豆を用いた大豆飲料の開発

  島田太一, 別府史章, 庭野吉己, 北川昭夫, 上東亨子, 佐藤恵美子, 河野雅弘

  月刊 FOOD STYLE21 食品の機能と健康を考える化学情報誌 142 3 86 - 89 食品化学新聞社 2009年 [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 62回 278 - 278 (公社)日本栄養・食糧学会 2008年04月 [査読有り][通常論文]
  
• 9trans,11trans conjugated linoleic acid inhibits the development of azoxymethane-induced colonic aberrant crypt foci in rats

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

  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.

書籍等出版物

• 脂質・脂肪酸関連物質の使いこなし方 : 素材開発・機能創生・応用技術

  石井, 淑夫 (担当:分担執筆範囲:水産脂質の栄養機能性)
  テクノシステム 2020年09月 (ISBN: 9784924728868) 3, 15, 592p

講演・口頭発表等

• 水産物由来エーテル型脂質の健康機能性  [招待講演]

  別府史章

  第6回脂質駆動学術産業創生研究部会 2024年10月 口頭発表（招待・特別）
• マウス筋損傷モデルを用いたエーテル型脂質の筋形成制御作用の検討

  今村響介, 高谷直己, 細川雅史, 別府史章

  第62回日本油化学会年会 2024年09月 口頭発表（一般）
• 褐藻フコキサンチンの高齢マウスにおける食餌誘導性肥満に与える影響

  川添 朱鞠, 高谷 直己, 別府 史章, 細川 雅史

  日本栄養・食糧学会大会講演要旨集 2024年04月 (公社)日本栄養・食糧学会
  
• マクロファージに対するアポ-12'-カプソルビナールの炎症抑制およびNrf2活性化効果

  高谷 直己, 宮房 拓生, 山野 由美子, 別府 史章, 細川 雅史

  日本栄養・食糧学会大会講演要旨集 2024年04月 (公社)日本栄養・食糧学会
  
• 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 2024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年
• 未利用水産生物の可能性を拡げる脂質機能性研究

  別府史章

  日本栄養・食糧学会大会講演要旨集 2023年 口頭発表（招待・特別）
• 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 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 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年
• 水産物由来エーテル脂質の新たな健康機能性を探る  [招待講演]

  別府史章

  日本栄養・食糧学会北海道支部シンポジウム講演要旨集 2022年 口頭発表（招待・特別）
• 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年
• 低次栄養段階生物を対象とした「かいあし漁業」の可能性を探る

  山口篤, 松石隆, 向井徹, 藤森康澄, 別府史章, 細川雅史

  日本ベントス学会・日本プランクトン学会合同大会講演要旨集 2021年
• 低次栄養段階生物を対象とした「かいあし漁業」の可能性を探る

  山口篤, 松石隆, 向井徹, 藤森康澄, 別府史章, 細川雅史

  日仏海洋学会学術研究発表会講演要旨集 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年
• 低次栄養段階生物を対象とした「かいあし漁業」の可能性を探る

  山口篤, 松石隆, 向井徹, 藤森康澄, 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 2020年
• 水産脂質による骨格筋機能改善効果

  別府史章

  飯島藤十郎記念食品科学振興財団年報 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 2020年
• 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 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 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 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 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 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 2019年
• ¹³Cを用いたトリアシルグリセロール脂肪酸結合位置と脂肪酸種の違いが脂肪酸体燃焼性に及ぼす影響の精査

  後藤直宏, 山谷好生, 別府史章, 別府史章, 吉永和明, 吉永和明, 永井利治

  日本油化学会年会講演要旨集 2019年
• ¹³Cを用いた脂肪酸の体燃焼性に及ぼすカルシウム添加効果

  吉永和明, 吉永和明, 山谷好生, 別府史章, 別府史章, 永井利治, 後藤直宏

  日本油化学会年会講演要旨集 2019年
• 海洋生物由来ビタミンEによる脂肪細胞への分化誘導能

  別府史章, 相田祐介, 金子昌弘, 笠谷聡, 青木由典, 後藤直宏

  日本栄養・食糧学会大会講演要旨集 2018年
• RAW264.7細胞におけるテトラコサヘキサエン酸の抗炎症作用評価

  安藤まなみ, 吉永和明, 後藤直宏, 別府史章

  日本油化学会年会講演要旨集 2018年
• マウスの脳におけるドコサテトラエン酸の蓄積機構

  石川榛那, 吉永和明, 別府史章, 後藤直宏

  日本油化学会年会講演要旨集 2018年
• 海洋性ビタミンE(Marine-derived tocopherol)の脂肪細胞分化に対する影響

  相田祐介, 別府史章, 後藤直宏

  日本水産学会大会講演要旨集 2017年
• 海洋性ビタミンE(Marine-derived tocopherol)の体内組織分布に関する研究

  別府史章, 近藤仁美, 後藤直宏

  日本栄養・食糧学会大会講演要旨集 2017年
• 食後高トリグリセライド血症を治療ターゲットとしたメトホルミン投与法の検討

  佐藤大介, 森野勝太郎, 村田幸一郎, 中川史之, 関根理, 別府史章, 後藤直宏, 卯木智, 前川聡

  糖尿病(Web) 2017年
• キヒトデ(Aterias amurensis)抽出油による高脂肪食摂取マウスの脂質代謝改善効果

  別府史章, 李皓き, 吉永和明, 永井利治, 吉田明彦, 後藤直宏

  日本水産学会大会講演要旨集 2017年
• 食用油脂中の飽和脂肪酸を結合したトリアシルグリセロール異性体の直接分離

  木下徹亮, 永井利治, 吉田明彦, 吉永和明, 別府史章, 後藤直宏

  日本油化学会年会講演要旨集 2017年
• 油脂中に含まれているラクトン及び遊離脂肪酸の同時定量法の開発

  小尾純志, 吉永和明, 永井利治, 吉田明彦, 別府史章, 後藤直宏

  日本油化学会年会講演要旨集 2017年
• 海洋性ビタミンEの探索と機能性

  別府史章

  日本油化学会年会講演要旨集 2016年
• 海洋性ビタミンE(Marine-derived tocopherol)の組織への蓄積に関する研究

  近藤仁美, 別府史章, 後藤直宏

  日本水産学会大会講演要旨集 2016年
• トランス脂肪酸異性体間の組織への蓄積と異化効率の違い

  別府史章, 浅沼公晴, 河村芳徳, 永井利治, 吉永和明, 溝部帆洋, 小島浩一, 笠谷聡, 永尾晃治, 久保篤史, 神田穣太, 後藤直宏

  日本栄養・食糧学会大会講演要旨集 2016年
• バターの脂肪酸組成および香気成分の季節変動

  吉永和明, 小尾純志, 永井利治, 吉田明彦, 別府史章, 後藤直宏

  日本油化学会年会講演要旨集 2016年
• 油脂中に含まれているラクトンの簡易的分析法の構築

  小尾純志, 吉永和明, 永井利治, 吉田明彦, 別府史章, 後藤直宏

  日本油化学会年会講演要旨集 2016年
• 過酸化脂質がラットの異食性および自発運動量へ与える影響

  別府史章, 北村風季, 渡邊浩幸, 後藤直宏

  日本油化学会年会講演要旨集 2015年
• 鶏卵を構成するトリアシルグリセロール異性体の分析

  後藤直宏, 石川桂子, 永井利治, 吉永和明, 溝部帆洋, 小島浩一, 別府史章

  日本油化学会年会講演要旨集 2015年
• キラルHPLCによる食用油脂トリアシルグリセロール位置異性体・鏡像異性体の同時分離

  永井利治, 石川桂子, 渡邊菜採子, 吉永和明, 溝部帆洋, 小島浩一, 別府史章, 後藤直宏

  日本油化学会年会講演要旨集 2015年
• 乳脂肪を構成するトリアシルグリセロール(TAG)異性体の分析

  渡邊菜採子, 永井利治, 吉永和明, 溝部帆洋, 小島浩一, 別府史章, 後藤直宏

  日本油化学会年会講演要旨集 2015年
• GC-FIDによる食用油脂トリアシルグリセロールの高精度分析法の構築

  吉永和明, 秋山由美, 永井利治, 溝部帆洋, 小島浩一, 別府史章, 後藤直宏

  日本油化学会年会講演要旨集 2015年
• 食用油脂中トリアシルグリセロールにおけるトランス脂肪酸の位置特異的分析  [通常講演]

  吉永和明, 河村芳徳, 北山敬, 永井利治, 溝部帆洋, 小島浩一, 渡辺嘉, 佐藤伸一, 別府史章, 後藤直宏

  日本油化学会年会講演要旨集 2014年09月
• 新規イオン液体カラムSLB-IL111を用いた食用油脂中のシスおよびトランスオクタデセン酸異性体のGC-FID分析

  吉永和明, 浅沼公晴, 永井利治, 溝部帆洋, 小島浩一, 別府史章, 後藤直宏

  日本油化学会年会講演要旨集 2013年
• HPLC-Nano quantity analyte detector(NQAD)を用いたトリアシルグリセロール分子種の新規定量分析方法の開発

  別府史章, 吉永和明, 永井利治, 溝部帆洋, 小島浩一, 後藤直宏

  日本油化学会年会講演要旨集 2013年
• ラット乳脂肪中のトリアシルグリセロール分子種の定量

  後藤直宏, 渡邊菜採子, 永井利治, 吉永和明, 溝部帆洋, 小島浩一, 北村洋平, 清水隆司, 別府史章

  日本油化学会年会講演要旨集 2013年
• LC/MSによる短鎖・中鎖脂肪酸を含む乳脂トリアシルグリセロール位置異性体および鏡像異性体の定量

  永井利治, 渡邊菜採子, 吉永和明, 溝部帆洋, 小島浩一, 別府史章, 齋藤忠夫, 後藤直宏

  日本油化学会年会講演要旨集 2013年
• 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年
• 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 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 2010年
• 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年

所属学協会

• 日本脂質生化学会   日本栄養・食糧学会   日本油化学会   日本水産学会   

共同研究・競争的資金等の研究課題

• 低次栄養段階生物を対象とした「かいあし漁業」の可能性を探る

  日本学術振興会：科学研究費助成事業 挑戦的研究(開拓)

  研究期間 : 2020年07月 -2026年03月 

  代表者 : 山口 篤, 松石 隆, 向井 徹, 藤森 康澄, 別府 史章

   

  今年度はかいあし漁業の内容を広く一般に普及させるための情報発信を主に行った。国内学会の発表２件に加え、Fish of the Month (FoM) という、北海道大学水産学部の研究成果を紹介するHPにおいて、本科研費の研究分担者を主とする５名による、かいあし漁業に関する内容を紹介した。紹介内容と紹介者は以下の通りである：「海洋生態系におけるカイアシ類の重要性とかいあし漁業への夢（山口 篤）」、「カイアシ類の音響探知（向井 徹）」、「カイアシ類の音響散乱特性（福田美亮）」、「カイアシ類を対象とした商業漁業（藤森康澄）」、「カイアシ類-新たな水産脂質供給源として（別府史章）」。 カイアシ類を対象とした研究論文として、北太平洋亜寒帯域に優占する日周鉛直移動を行うカイアシ類Metridia pacificaの一次生産への摂餌インパクトを推定し、呼吸量による輸送量の推定を行った。これは、表層（0-50 m）と深海（50-200 m）の水温条件下において、同種の雌成体を飼育し、呼吸による酸素消費量を測定し、現場の表層における摂餌量の推定と、深海における呼吸による炭素輸送量を推定したものである。夜間の表層における個体数は１平方メートルあたり27～5422個体の間にあり、昼間の表層には本種は出現せず、これは日周鉛直移動の反映と考えられた。日周鉛直移動バイオマスは、１平方メートルあたり1-309 mg Cであった。1日の夜間表層と昼間深海での滞留時間を考慮すると、1日あたり１平方メートルあたりの摂餌量は0.04-11.04 mg Cと推定され、これは現場一次生産量の0-2.4％を占めていた。一方、昼間深海での1日あたり１平方メートルあたりの呼吸量は0.02-9.39 mg Cと計算された。これは有光層からの沈降粒子輸送量の0-10％に相当しており、物質循環における重要性が示された。
• 水産資源由来脂質による筋機能改善効果とその作用機構解析

  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 : 2020年04月 -2023年03月 

  代表者 : 別府 史章

   

  超高齢社会にある我が国において、生活習慣病や要介護の問題を背景に骨格筋機能の維持は非常に重要な健康課題である。本研究では食品因子によるアプローチを目的とし、特に水産物由来脂質成分の骨格筋機能への有効性を検討している。 筋分化促進効果を示すイトマキヒトデ脂質のホスファチジルコリン（PC）画分について、PCサブクラス組成比をHPLC分析すると、ジアシル型PCに加え、アルキルアシル型PCが約40%、プラスマローゲン型PCが約10%含まれることが分かった。そこで、これらの活性を比較評価したところ、筋管形成促進効果はサブクラス間で異なることを見出した（未発表、投稿準備中）。また、ヒトデPC処理した細胞では筋管マーカーであるミオシン重鎖の発現増加が認められるとともに、他臓器と連関したエネルギー代謝調節に関わるマイオカインIL-15のmRNA発現量にも増加が認められた。さらに、筋委縮関連遺伝子MuRF1およびatrogin-1 mRNA、これらの発現を制御する転写因子FoxOの核内タンパク質発現量が低下し、ヒトデPCの筋タンパク質代謝制御作用を介した筋委縮予防の有効性が示唆された。一方、対照で用いた大豆PCでは、筋管サイズの増大や関連する遺伝子発現量に変化は認められなかった。以上、本研究ではPCサブクラス間での筋分化における作用の違いが示され、特有な分子構造とその組成を持つヒトデ脂質の優れた健康機能性の新たな可能性が示唆された。 その他、優れた筋形成促進効果を示す脂質素材を新たに見出し、in vivo試験への研究展開に有用な知見が得られた。
• 新規VE同族体の探索と機能性解明研究

  日本学術振興会：科学研究費助成事業 若手B

  研究期間 : 2018年04月 -2020年03月 

  代表者 : 別府 史章

   

  ビタミンE(VE)の分子構造による生理機能性の違いを明らかにするために、希少な同族体であるα-, β-, γ-, δ-トコモノエノール(T1)、トコジエノール(T2)を用いた機能解析を行った。まず始めに、（１）それぞれのT1、T2の調製を各種T3に部分水素添加することで簡便に調製可能であることを示した。これにより、（２）LC-MS/MSを用いたこれらVE同族体の分析手法を確立し、（３）糖尿病モデルマウスを用いて、T1およびT2による血糖値改善効果を明らかにするとともに、VE同族体の代謝特性についての新たな知見を得た。培養細胞系による機能解析により構造に起因する炎症抑制効果の違いが示唆された。
• 魚油が特異的に含む各種長鎖モノエン型脂肪酸位置異性体と体脂肪蓄積抑制能の関係解明

  日本学術振興会：科学研究費助成事業 基盤B

  研究期間 : 2016年04月 -2018年03月 

  代表者 : 後藤直宏
• 海洋性ビタミンEによる生体内酸化ストレスに対する防御機能解析

  日本学術振興会：科学研究費助成事業 若手B

  研究期間 : 2014年04月 -2017年03月 

  代表者 : 別府 史章

   

  海洋生物に特徴的に存在するビタミンE(MDT)の効率的な抽出精製方法を確立し、①代謝特性、②脂肪細胞分化に対する影響、③炎症抑制効果を明らかにした。 ①MDTは全身に広く分布するが、特に脂肪組織へ多く蓄積されることが確認された。②前駆脂肪細胞3T3-L1に対して、分化を制御するPPARγ、C/EBPαの発現増加を介して分化を促進することが示された。③MDT処理した3T3-L1およびマクロファージ様細胞RAW264.7の炎症性サイトカイン産生量の低減効果が認められた。②および③の効果の一部は他のビタミンＥ同族体よりも強く、その作用機序や活性は化学構造に基づくMDTの特徴的なものであると考えられる。
• フコキサンチンの生体内脂質代謝制御機構の解明

  日本学術振興会：科学研究費助成事業 特別研究員奨励費

  研究期間 : 2011年 -2012年 

  代表者 : 別府 史章

   

  ワカメやコンブなどの褐藻類に特徴的なカロテノイドであるフコキサンチン(以下Fx)は、抗肥満効果を有する食品素材として今後の活用が期待されている。本研究ではFxの強い抗肥満作用機構を明らかにすることを目的に、実験動物を用いて脂質代謝制御機構への影響を検討した。 これまでの研究により、Fxの抗肥満効果にレプチンシグナルが関わっていることを肝臓におけるレプチンのターゲット因子である脂肪酸不飽和化酵素SCD1の発現抑制作用から明らかにした。本研究では、Fxとレプチンシグナルの関連性を明らかにすることを目的とし、レプチンを欠損する肥満ob/obマウスに対するFxの影響を検討した。その結果、KK-Ayマウスで認められた肥満や高血糖の改善効果および肝臓SCD1の発現抑制作用は認められなかった。これらの結果より、Fxの抗肥満効果や血糖値改善効果がレプチン依存的であることを明らかにし、Fxがレプチン抵抗性の改善作用を有する、肥満予防に有望な食品素材であることを示す重要な知見が得られた。 一方、げっ歯類を用いた試験で報告されているFxの血中コレステロール上昇作用について、これまでに肝臓におけるLDL受容体およびスカベンジャー受容体(SR-B1)を介した、コレステロールおよびリポタンパクの取り込み低下に起因することを示した。さらに本研究では、コレステロール代謝調節に関わる転写因子であるSREBP2の発現上昇と、それにより転写調節を受けるPCSK9の遺伝子発現レベルがFxにより肝臓で増加することを新たに見出した。 PCSK9はLDL受容体タンパク質分解作用が報告されており、これらがFxによる血中コレステロール上昇作用に一部関わることが明らかとなった。以上の結果は、生体内の脂質運搬を担うリポタンパク質の代謝にもFxが影響することを示唆する重要な知見である。