Involvement of the pancreas-brain-liver inter-organ network and intestinal microbiota in hyper-nutritional fatty liver disease
| Project/Area Number |
17K01855
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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 |
Applied health science
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| Research Institution | Oita University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
正木 孝幸 大分大学, 医学部, 准教授 (00423715)
後藤 孔郎 大分大学, 医学部, 講師 (10457624)
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| Project Period (FY) |
2017-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 膵β細胞特異的TNFα過剰発現マウス / 糖尿病抵抗性・肥満抵抗性・脂肪肝抵抗性 / 恒常的バゾプレッシン(AVP)増加 / 機能的グルカゴン低下 / 組織特異的グルカゴン作用 / 腸内細菌叢 / 肝臓メタボローム解析 / 求心性迷走神経遮断 / 機能性グルカゴンの低下 / インスリン感受性亢進 / AVP / 嫌気性代謝亢進 / 迷走神経遮断 / 糖尿病抵抗性 / 肥満抵抗性 / 脂肪肝抵抗性 / 免疫染色 / インスリン / グルカゴン / ソマトスタチン / 脂肪合成低下 / アミノ酸代謝亢進 / インスリン分泌 / Firmicutes / Verrucomicrobia / 臓器間ネットワーク |
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| Outline of Final Research Achievements |
Pancreatic β-cell specific TNFα transgenic mice (TNFαTg mice) are resistant to diabetes despite apparent Insulitis. In addition, since it showed resistance to obesity and fatty liver (accompanied by a decrease in liver weight) against overnutrition, the mechanism was analyzed. Since no elevation of TNFα in the blood was observed, we assumed the possibility that hormonal dysfunction in the pancreas due to TNFα paracrine might cause this phenotype via the central nervous system, but it was negative. Therefore, it is speculated that this characteristic phenotype was formed through humoral information through blood and changes in the intestinal environment through pancreatic exocrine secretion.
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| Academic Significance and Societal Importance of the Research Achievements |
膵臓―脳―肝臓の臓器間ネットワークの存在や、それによる過栄養性脂肪肝発症の新規メカニズムの解明には至らなかったが、膵臓局所での微細なホルモン動態の変化が、血液を介した液性情報として、また外分泌機能を介した腸内環境の変化を介して、糖尿病抵抗性、肥満抵抗性、脂肪肝抵抗性に関与することが判明した。中でも、VerrucomicrobiaやActinobacteriaといった腸内細菌の肥満抑制、代謝改善に関わる影響が大きい可能性を示している。
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Report
(7 results)
Research Products
(5 results)
