Researcher Database
Last Updated :2024/07/25
researchmap
Profile and Settings
Affiliation
Profile and Settings
Name (Japanese)
TakataniName (Kana)
NaokiName
202101007440911542
Alternate Names
Affiliation
Achievement
Research Interests
- marine carotenoids carotenoids metabolites Apocarotenoids chronic inflammatory diseases lifestyle-related diseases marine bacteria
Research Areas
Research Experience
- 2021/04 - Today Hokkaido University Faculty of Fisheries Sciences
- 2019/04 - 2021/03 日本学術振興会 特別研究員(DC2)
- 2015/04 - 2018/03 フジッコ株式会社
Education
- 2018/04 - 2021/03 Hokkaido University Graduate School of Fisheries Sciences
- 2013/04 - 2015/03 Hokkaido University Graduate School of Fisheries Sciences
- 2009/04 - 2013/03 Hokkaido University School of Fisheries Sciences Department of Marine Bioresources Chemistry
Awards
Published Papers
- Naoki Takatani, Takashi Maoka, Tomoo Sawabe, Fumiaki Beppu, Masashi HosokawaApplied microbiology and biotechnology 108 (1) 102 - 102 2024/01 [Refereed]
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. - Yuka Tojo, Toshiaki Kamitani, Naoki Takatani, Toshiya Toda, Toshio Suzuki, Seiichiro AoeFood Science and Technology Research 29 (4) 331 - 337 1344-6606 2023 [Refereed]
- Naoki Takatani, Kana Sakimura, Kodai Nagata, Fumiaki Beppu, Yumiko Yamano, Takashi Maoka, Masashi HosokawaFood chemistry 410 135318 - 135318 2022/12/28 [Refereed]
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. - Kodai Nagata, Naoki Takatani, Fumiaki Beppu, Aya Abe, Etsuko Tominaga, Tomohisa Fukuhara, Makoto Ozeki, Masashi HosokawaMarine Drugs 20 (7) 446 - 446 2022/07/07 [Refereed]
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. - Naoki Takatani, Fumiaki Beppu, Yumiko Yamano, Takashi Maoka, Kazuo Miyashita, Masashi HosokawaACS OMEGA 7 (26) 22341 - 22350 2470-1343 2022/06 [Refereed]
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. - Masaki Kakimoto, Naoki Takatani, Masashi Hosokawa, Fumiaki BeppuFisheries Science 0919-9268 2022 [Refereed]
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. - Liping Chen, Fumiaki Beppu, Naoki Takatani, Kazuo Miyashita, Masashi HosokawaFISHERIES SCIENCE 87 (5) 727 - 737 0919-9268 2021/09 [Refereed]
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. - Naoki Takatani, Fumiaki Beppu, Yumiko Yamano, Takashi Maoka, Masashi HosokawaJournal of oleo science 70 (4) 549 - 558 2021/04/02 [Refereed]
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. - Naoki Takatani, Daisuke Taya, Ami Katsuki, Fumiaki Beppu, Yumiko Yamano, Akimori Wada, Kazuo Miyashita, Masashi HosokawaMolecular nutrition & food research 65 (2) e2000405 2021/01 [Refereed]
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. - Naoki Takatani, Yuka Kono, Fumiaki Beppu, Yuko Okamatsu-Ogura, Yumiko Yamano, Kazuo Miyashita, Masashi HosokawaBiochemical and biophysical research communications 528 (2) 305 - 310 2020/07/23 [Refereed]
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. - Liping Chen, Naoki Takatani, Fumiaki Beppu, Kazuo Miyashita, Masashi HosokawaNutrients 11 (12) 2019/11/22 [Refereed]
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. - Jiro Koizumi, Naoki Takatani, Noritoki Kobayashi, Koji Mikami, Kazuo Miyashita, Yumiko Yamano, Akimori Wada, Takashi Maoka, Masashi HosokawaMarine drugs 16 (11) 2018/11/01 [Refereed]
Carotenoids are natural pigments that contribute to light harvesting and photo-protection in photosynthetic organisms. In this study, we analyzed the carotenoid profiles, including mono-hydroxy and epoxy-carotenoids, in the economically valuable red seaweed Pyropia yezoensis, to clarify the detailed biosynthetic and metabolic pathways in the order Bangiales. P. yezoensis contained lutein, zeaxanthin, α-carotene, and β-carotene, as major carotenoids in both the thallus and conchocelis stages. Monohydroxy intermediate carotenoids for the synthesis of lutein with an ε-ring from α-carotene, α-cryptoxanthin (β,ε-caroten-3'-ol), and zeinoxanthin (β,ε-caroten-3-ol) were identified. In addition, β-cryptoxanthin, an intermediate in zeaxanthin synthesis from β-carotene, was also detected. We also identified lutein-5,6-epoxide and antheraxanthin, which are metabolic products of epoxy conversion from lutein and zeaxanthin, respectively, by LC-MS and ¹H-NMR. This is the first report of monohydroxy-carotenoids with an ε-ring and 5,6-epoxy-carotenoids in Bangiales. These results provide new insights into the biosynthetic and metabolic pathways of carotenoids in red seaweeds. - Naoki Takatani, Tomoo Sawabe, Takashi Maoka, Kazuo Miyashita, Masashi HosokawaBIOCATALYSIS AND AGRICULTURAL BIOTECHNOLOGY 4 (2) 174 - 179 1878-8181 2015/04 [Refereed]
Gillisia lirtinaea strain DSM 15749 (=R-8282(T), =LMG21470,=CIP108418) is a Gram-negative, strictly aerobic, psychrophilic, and non-photosynthetic bacterium that belongs to the family Flavobacteriaceae, which was isolated from a microbial mat in Lake Fryxell, Antarctica (Van. Trapp en eI. al., 2004). The bacteriurn shows yellow colored colony, but the cat otenoid composition has never been determined yet. In this study, we elucidated the structure of carotenoids produced by the strain DSM 15749. G. lirtinaea strain DSM 15749 synthesized a novel monocyclic-type carotenoid, 3 ''-hydroxy-2'-isopentenylsaproxanthin ((3R, 2'S')-2 '-(3-hydroxy-3-methylbutyl)-3 '', 4'-didehydro-1', 2'-dihydro-beta, Psi-carotene-3, 1'-diol), as well as (3R, TR)-zeaxanthin. Furthermore, another monocyclic carotenoid, 2'-isopentenylsaproxanthin, was also detected in the strain DSM 15749. 3 ''-Hydroxy-2'-isopentenylsaproxanthin is "Chimera'like unique structures, in that one end group forms the same structure of zeaxanthin, and the other end group is the same as bacterioruberin which is produced by several extremophilic bacteria and archaea. This structure involved the hydroxy derivative of 2'-isopentenylsaproxanthin. The present study is the First report about the carotenoids produced by the genus Gillisto, of the family Flavobacteriaceae. (C) 2015 Elsevier Ltd. All rights reserved. - Naoki Takatani, Masato Nakanishi, Pedro Meirelles, Sayaka Mino, Wataru Suda, Kenshiro Oshima, Masahira Hattori, Moriya Ohkuma, Masashi Hosokawa, Kazuo Miyashita, Fabiano L Thompson, Ako Niwa, Toko Sawabe, Tomoo SawabeGenome announcements 2 (6) 2014/12/04 [Refereed]
Here, we present the draft genome sequence of a novel carotenoid 2'-isopentenylsaproxanthin producer, Jejuia pallidilutea strain 11shimoA1, isolated from the surface of seaweed in Japan, and the ethyl methanesulfonate-induced pigmentation mutants. This genomic information will help to not only elucidate the 2'-isopentenylsaproxanthin biosynthetic pathway but also understand the evolution of flavobacteria. - Masato Nakanishi, Pedro Meirelles, Ryohei Suzuki, Naoki Takatani, Sayaka Mino, Wataru Suda, Kenshiro Oshima, Masahira Hattori, Moriya Ohkuma, Masashi Hosokawa, Kazuo Miyashita, Fabiano L Thompson, Ako Niwa, Toko Sawabe, Tomoo SawabeGenome announcements 2 (6) 2014/11/13 [Refereed]
Here, we present the draft genome sequences of six carotenoid producers affiliated with Nonlabens spp. isolated from marine environments in both the northern and southern parts of Japan. The genomic information will help to elucidate the function and evolution of carotenoid synthetic gene clusters not only in the genus Nonlabens but also in the family Flavobacteriaceae. - Naoki Takatani, Masato Nakanishi, Pedro Meirelles, Sayaka Mino, Wataru Suda, Kenshiro Oshima, Masahira Hattori, Moriya Ohkuma, Masashi Hosokawa, Kazuo Miyashita, Fabiano L Thompson, Ako Niwa, Toko Sawabe, Tomoo SawabeGenome announcements 2 (6) 2014/11/13 [Refereed]
Here, we present the draft genome sequences of a zeaxanthin-producing flavobacterium, Algibacter lectus strains SS8 and NR4, isolated from coastal sediment and rock surfaces in Hakodate, Japan, respectively. This genomic information represents the first Algibacter genome sequences, which will help us to elucidate the biology and evolution of Flavobacteriaceae bacteria. - Naoki Takatani, Kentaro Nishida, Tomoo Sawabe, Takashi Maoka, Kazuo Miyashita, Masashi HosokawaApplied microbiology and biotechnology 98 (15) 6633 - 40 2014/08 [Refereed]
Carotenoids are a class of naturally occurring pigment, carrying out important biological functions in photosynthesis and involved in environmental responses including nutrition in organisms. Saproxanthin and myxol, which have monocyclic carotenoids with a γ-carotene skeleton, have been reported to show a stronger antioxidant activity than those with β-carotene and zeaxanthin. In this research, a yellow-orange bacterium of strain 11shimoA1 (JCM19538) was isolated from a seaweed collected at Nabeta Bay (Shizuoka, Japan). The 16S rRNA gene sequence of strain 11shimoA1 revealed more than 99.99 % similarity with those of Jejuia pallidilutea strains in the family Flavobacteriaceae. Strain 11shimoA1 synthesized two types of carotenoids. One of them was (3R, 3'R)-zeaxanthin with dicyclic structure and another was identified as (3R, 2'S)-2'-isopentenylsaproxanthin, a novel monocyclic carotenoid with pentenyl residue at C-2' position of saproxanthin, using FAB-MS, (1)H NMR, and CD analyses. Culturing strain 11shimoA1 in an alkaline medium at pH 9.2 resulted in a markedly increased in production of 2'-isopentenylsaproxanthin per dry cell weight, but a decreased in zeaxanthin production as compared to their respective production levels in medium with pH 7.0. These carotenoids are likely to play some roles in the adaptation of the bacterium to the environmental conditions.
MISC
- アポカロテノイドの動物細胞への生理活性（第22章）高谷直己, 細川雅史 カロテノイドの科学-基礎,研究の新展開,生理活性-（シーエムシー出版） 228 -235 2024/03
- 褐藻フコキサンチンの非アルコール性脂肪肝炎予防効果と生体利用率の向上（第19章）細川雅史, 高谷直己 カロテノイドの科学-基礎,研究の新展開,生理活性-（シーエムシー出版） 201 -208 2024/03
- アポカロテノイドの同定と細胞機能調節作用に関する研究高谷 直己 一般財団法人 食品分析開発センターSUNATECメールマガジン 2023/08
- アポカロテノイドの細胞機能調節作用高谷 直己 アグリバイオ 7- (4) 338 -341 2023/03 [Not refereed]
- 高谷 直己 オレオサイエンス 21- (5) 179 -181 2021/05 [Not refereed]
- 高谷 直己 Carotenoid Science 24- 61 2020 [Not refereed]
- 高谷 直己, 細川 雅史 生物工学会誌 98- (10) 529 -532 2020 [Not refereed]
Presentations
- 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 [Not invited]川添朱鞠, 高谷直己, 別府史章, 細川雅史第78回日本栄養・食糧学会大会 2024/05
- 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 [Not invited]高谷直己, 宮房拓生, 山野由美子, 別府史章, 細川雅史第78回日本栄養・食糧学会大会 2024/05
- 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, 細川雅史令和6年度日本水産学会大会春季大会 2024/03
- アスタキサンチン由来アポカロテノイドの調製と生理活性評価 [Not invited]高谷直己, 別府史章, 山野由美子, 眞岡孝至, 細川雅史第35回カロテノイド研究談話会 2023/11
- フコキサンチン由来生体内開裂物の同定と活性化マクロファージおよび脂肪細胞に対する抗炎症作用 [Not invited]高谷直己, 別府史章, 細川雅史第9回北大・部局横断シンポジウム 2023/10
- フコキサンチンの非アルコール性脂肪肝炎モデルマウスに対する予防機構 [Not invited]池田詩歩, 高谷直己, 別府史章, 細川雅史第9回北大・部局横断シンポジウム 2023/10
- 海洋細菌Algoriphagus sp. oki45株が産生する新規カロテノイドの同定と生合成遺伝子の推定 [Not invited]高谷直己, 土橋祐汰, 澤辺智雄, 眞岡孝至, 別府史章, 細川雅史日本油化学会第61回年会 2023/09
- Fucoxanthinおよびその代謝物による樹状細胞の炎症制御作用 [Not invited]七戸優斗, 高谷直己, 別府史章, 細川雅史日本油化学会第61回年会 2023/09
- フコキサンチンの非アルコール性脂肪性肝炎モデルマウスに対する予防機構 [Not invited]池田詩歩, 高谷直己, 別府史章, 細川雅史日本油化学会第61回年会 2023/09
- Identification and tissue distribution of fucoxanthin-derived novel metabolites [Not invited]Naoki Takatani, Kana Sakimura, Fumiaki Beppu, Yumiko Yamano, Takashi Maoka, Masashi HosokawaThe 19th International Symposium on Carotenoids 2023/07
- Identification of novel monocyclic carotenoids in marine bacteria and their bioactivity [Not invited]Masashi Hosokawa, Naoki Takatani, Fumiaki Beppu2023 AOCS Annual Meeting & Expo 2023/05
- Identification of novel and rare carotenoids from marine bacteria and their biosynthesis [Not invited]Naoki TakataniTaiwan-Japan International Symposium on Marine Science 2023/05
- 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 [Not invited]高谷直己, 向村奏, 別府史章, 細川雅史令和5年度日本水産学会大会春季大会 2023/03
- Identification of novel carotenoids from marine bacteria and their bioactivity [Invited]Naoki Takatani, Masashi Hosokawa2nd World Congress on Oleo Science (WCOS 2022) 2022/09
- フコキサンチン由来新規生体内代謝物の同定と組織分布解析 [Not invited]高谷直己, 向村奏, 別府史章, 山野由美子, 眞岡孝至, 細川雅史第34回カロテノイド研究談話会 2022/09
- 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 [Not invited]高谷直己, 向村奏, 永田航大, 田谷大輔, 別府史章, 細川雅史第76回日本栄養・食糧学会大会 2022/06
- 褐藻由来フコキサンチンによる非アルコール性脂肪肝炎抑制効果 [Not invited]高谷直己, 別府史章, 細川雅史第7回北大・部局横断シンポジウム 2021/09
- Identification of novel fucoxanthin cleavage metabolites and anti-inflammatory action against activated macrophages [Not invited]Naoki Takatani, Fumiaki Beppu, Takashi Okitsu, Yumiko Yamano, Masashi HosokawaThe 1st Virtual International Conference on Carotenoids 2021/06
- β-Carotene由来アポカロテノイドによる炎症抑制機構 [Not invited]高谷直己, 別府史章, 山野由美子, 沖津貴志, 眞岡孝至, 細川雅史日本油化学会第59回年会 2020/11
- 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 [Not invited]高谷直己, 河野友香, 別府史章, 宮下和夫, 細川雅史第74回日本栄養・食糧学会大会 2020/05
- アポカロテノイドの調製と細胞機能に関する研究 [Invited]高谷直己第7回若手研究者奨励賞記念講演会 2020/01
- 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 [Not invited]高谷直己, 別府史章, 宮下和夫, 細川雅史日本油化学会第58回年会 2019/09
- アポフコキサンチノイドによる炎症抑制機構解析 [Not invited]高谷直己, 別府史章, 沖津貴志, 山野由美子, 和田昭盛, 宮下和夫, 細川雅史第33回カロテノイド研究談話会 2019/09
- 海洋性カロテノイドfucoxanthinの新規生体内開裂物による炎症抑制機構 [Not invited]高谷直己, 田谷大輔, 宮下和夫, 細川雅史第73回日本栄養・食糧学会大会 2019/05
Association Memberships
Research Projects
- 日本学術振興会：科学研究費助成事業 若手研究Date (from‐to) : 2023/04 -2026/03Author : 高谷 直己
- Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)Date (from‐to) : 2021/04 -2024/03Author : 細川 雅史, 岡松 優子, 高谷 直己2021年度の研究において、以下の研究成果を得た。 (1)フコキサンチンを投与した肥満マウスの脂肪組織では、これまで報告しているように活性化マクロファージマーカーのF4/80およびM1マクロファージマーカーのCD11cのmRNA発現量の低下が確認された。さらに、M1マーカー(CD11c)/M2マーカー(Arg1)比も低下したことから、フコキサンチンがマクロファージの脂肪組織への浸潤を抑制するとともに、極性変化にも関わることが推察された。一方、T細胞マーカーを解析した結果、CD8に加えCD25およびCD4のmRNA発現量が低下し、T細胞サブセットへの影響が示唆された。(2)非アルコール性脂肪肝炎を誘導したマウスの肝臓では、フコキサンチンの投与によりCD8およびCD25のmRNA発現量が低下傾向を示した。(3)肝細胞およびマクロファージ株をフコキサンチン代謝物のフコキサンチノールで処理し、各オルガネラにおける蓄積をHPLCにて定量した。細胞膜、ミトコンドリア、ミクロソーム画分でフコキサンチノールが検出されたことから、細胞膜を通過しオルガネラへの移行することが推察された。特に、ミトコンドリア画分での蓄積が多いことが示唆された。(4)フコキサンチノールがミトコンドリア画分に蓄積していた点に着目し、ミトコンドリア機能に関わるミトコンドリアDNA量の測定を行った。NASHモデルマウスの肝臓からDNAを抽出し測定を行った結果、普通食群と比較してNASH誘導色群でみられたミトコンドリアDNA量の低下が、フコキサンチンにより抑制された。(5)エネルギー代謝に関わる白色脂肪組織から褐色脂肪組織への転換メカニズムとして分泌因子を介した細胞間コミュニケーションについて調べた。その結果、BMPを介した組織転換制御の可能性が認められた。
- Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Research Activity Start-upDate (from‐to) : 2021/08 -2023/03Author : 高谷 直己慢性腎臓病（CKD）は生活習慣病を背景に発症する慢性炎症疾患で、透析や腎移植が必要となる末期腎不全のみならず、心筋梗塞など心血管イベントの発症リスクを高める。未だCKDに対する有効な治療薬はなく、食品因子による炎症制御を介した予防方策が望まれている。そこで本年度は、CKDモデルマウスに、ワカメなどの褐藻に豊富に含まれる海洋性カロテノイドである「フコキサンチン」を投与した際の腎臓炎症に与える影響について検討を行った。健常タイプC57BL/6Jマウスにアデニンを含むAIN-93G飼料を給餌しCKDを誘導後、腎臓におけるmRNA発現解析を行った。その結果、対照区（通常食）と比較してCKD誘導区（アデニン含有食）の腎臓では、炎症性サイトカインをはじめとして、ケモカインであるMCP-1やマクロファージマーカーであるF4/80発現の著増を認めたことから、腎臓において炎症の亢進ならびにマクロファージの浸潤が増加している可能性が示唆された。一方、フコキサンチン投与区（フコキサンチン+アデニン含有食）の腎臓組織では、これら因子の発現増加が有意に抑制された。次に、フコキサンチンの生体内代謝物であるフコキサンチノールを用いて、HK-2近位尿細管細胞に対する抗炎症活性を評価した。HK-2細胞にTNFα添加することにより誘導される炎症性サイトカインやケモカインのmRNA発現上昇は、フコキサンチノール処置により有意に抑制された。さらに、THP-1マクロファージに対しても、LPS添加による炎症性サイトカインのmRNA発現増加に対して、フコキサンチノールによる抑制作用が観察された。以上より、フコキサンチン投与による腎臓炎症の緩和作用機序の一端に、腎臓に蓄積したフコキサンチノールによる腎臓細胞や免疫細胞に対する炎症制御作用が関わる可能性が推察される。
- 日本学術振興会：科学研究費助成事業 特別研究員奨励費Date (from‐to) : 2019/04 -2021/03Author : 高谷 直己メタボリックシンドロームの肝臓における表現型といわれる非アルコール性脂肪肝炎（NASH）は、肝臓の脂肪化（脂肪肝）をはじめとして、過剰な酸化ストレスの負荷、炎症の亢進を特徴とする。未だNASHに有効な治療薬はなく、食品因子による予防方策が望まれている。そこで本年度は、ワカメなどの褐藻に豊富に含まれる海洋性カロテノイドである「フコキサンチン」のNASH抑制作用について評価を行った。健常タイプC57BL/6Jマウスにコリン欠乏アミノ酸含量調整食を摂取させたところ、脂肪肝や肝障害が生じるとともに、肝臓における過酸化脂質の増加やTNFα等の炎症マーカーのmRNA発現の顕著な増加がみられ、NASHが誘導された。対して、フコキサンチン投与したマウスでは、脂肪肝や肝障害、肝過酸化脂質蓄積、炎症マーカーの発現増加がいずれも強く抑制された。さらに、NASH誘導マウスの肝臓組織では、コラーゲン等の線維化関連因子のmRNA発現が促進されたが、フコキサンチン投与により、線維化関連因子の発現とともに線維化に関わる肝星細胞の活性化が著明に抑制された。以上より、フコキサンチンは、NASHの増悪因子である肝脂肪化、酸化ストレスや炎症を抑制するのみならず、線維化の初期段階も抑制することが明らかとなった。一方、フコキサンチン投与マウスの肝臓脂質をHPLCにより分析したところ、脱アセチル化したフコキサンチノールや脱エポキシ化したアマロウシアキサンチンAに変換されていた。そこで、マウス由来肝実質細胞に脂肪蓄積を誘導するアッセイ系を確立し、これら代謝物を評価したところ、フコキサンチノールが飽和脂肪酸による脂肪蓄積を抑制することが分かった。従って、in vivoで見られたフコキサンチンのNASH抑制作用機序の一つに、代謝物であるフコキサンチノールによる肝脂肪化抑制を介している可能性が示唆された。