Identification of gut microbiota- derived metabolites and the mechanisms that impair glucose metabolism
| Project/Area Number |
17K09821
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | University of Toyama |
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Principal Investigator |
Fujisaka Shiho 富山大学, 学術研究部医学系, 助教 (30512082)
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| Co-Investigator(Kenkyū-buntansha) |
戸辺 一之 富山大学, 学術研究部医学系, 教授 (30251242)
薄井 勲 獨協医科大学, 医学部, 教授 (50377272)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | インスリン抵抗性 / 腸内細菌 / 腸内細菌叢 / 肥満 / 糖代謝異常 / 糖尿病 / 代謝産物 |
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| Outline of Final Research Achievements |
We analyzed plasma and cecal metabolomics data of genetically different mice treated with a high fat- diet and/or antibiotics and identified several metabolites that correlated with insulin resistance of the host（Fujisaka et al. Cell Reports. 22: 3072-3086, 2018）. We also reported that Bofutsushosan (BFT), a Japanese herbal medicine which has been clinically used for constipation in Asian countries, ameliorates glucose metabolism in mice with diet-induced obesity. As the mechanism, we found that BFT modified the gut microbiota, which may contribute to improving gut barrier function and preventing metabolic endotoxemia, leading to attenuation of diet-induced inflammation and glucose intolerance (Fujisaka et al. Sci. Rep. 10: 5544, 2020）.
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| Academic Significance and Societal Importance of the Research Achievements |
肥満やメタボリック症候群の人口は近年世界的に増加しており、その合併症を引き起こすインスリン抵抗性の病態を克服することは喫緊の課題である。本研究を通じ、腸内細菌叢が血中の代謝産物の量に大きな影響を及ぼし、それがインスリン抵抗性の病態に大きく関与することを見出した。また、漢方薬である防風通聖散が、腸内細菌叢を変化させることでインスリン抵抗性の病態を改善しうる多面的作用があることを見出した。インスリン抵抗性を制御する上での腸内細菌叢の新たな役割を明らかにできたと考えられる。
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Report
(4 results)
Research Products
(22 results)
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[Journal Article] Diet, Genetics, and the Gut Microbiome Drive Dynamic Changes in Plasma Metabolites.2018
Author(s)
Fujisaka S, Avila-Pacheco J, Soto M, Kostic A, Dreyfuss JM, Pan H, Ussar S, Altindis E, Li N, Bry L, Clish CB, Kahn CR.
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Journal Title
Ｃｅｌｌ Ｒｅｐｏｒｔｓ
Volume: 22
Issue: 11
Pages: 3072-3086
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Ratio of low molecular weight serum adiponectin to the total adiponectin value is associated with type 2 diabetes through its relation to increasing insulin resistance.2018
Author(s)
Iwata M, Hara K, Kamura Y, Honoki H, Fujisaka S, Ishiki M, Usui I, Yagi K, Fukushima Y, Takano A, Kato H, Murakami S, Higuchi K, Kobashi C, Fukuda K, Koshimizu Y, Tobe K.
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Journal Title
PLoS One
Volume: 13
Issue: 3
Pages: e0192609-e0192609
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Divergent effects of glucose and fructose on hepatic lipogenesis and insulin signaling.2017
Author(s)
Softic S, Gupta MK, Wang GX, Fujisaka S, O'Neill BT, Rao TN, Willoughby J, Harbison C, Fitzgerald K, Ilkayeva O, Newgard CB, Cohen DE, Kahn CR.
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Journal Title
Ｊｏｕｒｎａｌ ｏｆ Ｃｌｉｎｉｃａｌ Ｉｎｖｅｓｔｉｇａｔｉｏｎ
Volume: 127
Issue: 11
Pages: 4059-4074
DOI
Related Report
Peer Reviewed / Open Access
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