Novel therapy for obesity and diabetes through intestinal bile acid metabolism
| Project/Area Number |
18K08526
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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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| Review Section |
Basic Section 54040:Metabolism and endocrinology-related
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| Research Institution | Keio University |
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Principal Investigator |
IRIE Junichiro 慶應義塾大学, 医学部(信濃町), 講師 (70306687)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
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| Keywords | 肥満症治療 / 腸内環境 / 胆汁酸 / 腸内細菌叢 / 耐糖能障害 / 腸内細菌 / dysbiosis / メタボリックシンドローム / 肥満症 / 糖尿病 / 腸管 |
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| Outline of Final Research Achievements |
We have shown that the changes in bile acid metabolism in the intestinal tract cause a deviation in the intestinal microbiota and their function to metabolize the intestinal contents, resulting in the pathophysiology of obesity and diabetes. It was revealed that intestinal bile acids have important roles to determine the composition of the intestinal microbiota and the metabolism of bile acids in the intestine in subjects with obesity and diabetes. The increase in a high-fat diet-induced bile acid secretion would cause the deviation in the intestinal microbiota and the altered intestinal microbiota would make further changes in bile acid metabolism in the initiation of high-fat diet-induced obesity and diabetes in animals and humans.
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| Academic Significance and Societal Importance of the Research Achievements |
本検討は、高脂肪食による肥満症・糖尿病の発症において、エネルギー摂取の増加ではなく、食事の質の違いにより惹起される胆汁酸代謝の変化に注目したものであり、カロリー計算と三大栄養素の割合で論じることが多い現在の食事療法について、新たな解釈を可能とするものである。有効な治療法に乏しい肥満・糖尿病において、腸管機能の維持を意識した治療法の開発に繋がるものと考えている。本研究から得られた知見に基づき、食事の質に注目した新たな栄養処方、および腸管腔内に作用する新たな肥満・糖尿病治療薬物の開発が期待される。
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Report
(4 results)
Research Products
(56 results)
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[Journal Article] Contribution of uremic dysbiosis to insulin resistance and sarcopenia.2020
Author(s)
Uchiyama K, Wakino S, Irie J, Miyamoto J, Matsui A, Tajima T, Itoh T, Oshima Y, Yoshifuji A, Kimura I, Itoh H.
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Journal Title
Nephrol Dial Transplant.
Volume: 35
Issue: 9
Pages: 1501-1517
DOI
Related Report
Peer Reviewed
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[Journal Article] Maternal gut microbiota in pregnancy influences offspring metabolic phenotype in mice2020
Author(s)
Kimura I, Miyamoto J, Ohue-Kitano R, Watanabe K, Yamada T, Onuki M, Aoki R, Isobe Y, Kashihara D, Inoue D, Inaba A, Takamura Y, Taira S, Kumaki S, Watanabe M, Ito M, Nakagawa F, Irie J, Kakuta H, Shinohara M, Iwatsuki K, Tsujimoto G, Ohno H, Arita M, Itoh H, Hase K.
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Journal Title
Science
Volume: 367
Issue: 6481
Pages: 8429-8429
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Effect of oral administration of nicotinamide mononucleotide on clinical parameters and nicotinamide metabolite levels in healthy Japanese men2020
Author(s)
Irie J, Inagaki E, Fujita M, Nakaya H, Mitsuishi M, Yamaguchi S, Yamashita K, Shigaki S, Ono T, Yukioka H, Okano H, Nabeshima YI, Imai SI, Yasui M, Tsubota K, Itoh H
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Journal Title
Endocrine Journal
Volume: 67
Issue: 2
Pages: 153-160
DOI
NAID
ISSN
0918-8959, 1348-4540
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Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Efficacy and safety of once-weekly exenatide after switching from twice-daily exenatide in patients with type 2 diabetes2020
Author(s)
Watanabe Y, Saisho Y, Inaishi J, Kou K, Yamauchi A, Kanazawa Y, Okubo Y, Tokui M, Imai T, Murakami R, Tsuchiya T, Sasaki H, Masaoka T, Irie J, Meguro S, Itoh H
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Journal Title
J Diabetes Investig
Volume: 11
Issue: 2
Pages: 382-388
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Background characteristics and postoperative outcomes of insufficient weight loss after laparoscopic sleeve gastrectomy in Japanese patients.2019
Author(s)
Saiki A, Yamaguchi T, Tanaka S, Sasaki A, Naitoh T, Seto Y, Matsubara H, Yokote K, Okazumi S, Ugi S, Yamamoto H, Ohta M, Ishigaki Y, et al
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Journal Title
Ann Gastroenterol Surg.
Volume: 3
Issue: 6
Pages: 638-647
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Ketone body receptor GPR43 regulates lipid metabolism under ketogenic conditions2019
Author(s)
Miyamoto J, Ohue-Kitano R, Mukouyama H, Nishida A, Watanabe K, Igarashi M, Irie J, Tsujimoto G, Satoh-Asahara N, Itoh H, Kimura I
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Journal Title
Proc Natl Acad Sci USA
Volume: 116
Issue: 47
Pages: 23813-23821
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Gut microbiota confers host resistance to obesity by metabolizing dietary polyunsaturated fatty acids2019
Author(s)
Miyamoto J, Igarashi M, Watanabe K, Karaki SI, Mukouyama H, Kishino S, Li X, Ichimura A, Irie J, Sugimoto Y, Mizutani T, Sugawara T, Miki T, Ogawa J, Drucker DJ, Arita M, Itoh H, Kimura I
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Journal Title
Nat Commun
Volume: 10
Issue: 1
Pages: 1-15
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Association of Maternal Factors with Perinatal Complications in Pregnancies Complicated with Diabetes: A Single-Center Retrospective Analysis.2018
Author(s)
Endo S, Saisho Y, Miyakoshi K, Ochiai D, Matsumoto T, Kawano Y, Mitsuishi M, Irie J, Tanaka M, Meguro S, Tanaka M, Itoh H.
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Journal Title
J Clin Med
Volume: 7
Issue: 1
Pages: 5-5
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] 糖エネルギー代謝異常症と腸内細菌叢2019
Author(s)
入江潤一郎, 木村郁夫, 菊地理恵子, 加藤麻里, 田中久美子, 藤田真隆, 杉山和俊, 永久太一, 竹林駿太, 中島裕也, 山口慎太郎, 伊藤裕
Organizer
第92回日本内分泌学会学術総会
Related Report
Invited
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