| Project/Area Number |
16K19062
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Nihon University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | ビタミンD / 胆汁酸 / 核内受容体 / 肥満 / 腸内細菌 |
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| Outline of Final Research Achievements |
The aim of our research is to elucidate roles of vitamin D receptor (VDR) in the bile acid metabolism and gut microbiota in diet-induced obesity (DIO) mice. First, we confirmed that high fat diet (HFD) feeding didn’t increase body weight in VDR knockout (VDRKO) mice. Although HFD increased fecal total bile acids and secondary bile acids (e.g. lithocholic acid (LCA)) contents both wild type mice and VDRKO mice, VDR deficiency didn’t change bile acid contents and compositions. These data reveal that VDR deficiency represses weight gain by feeding HFD, but doesn’t change bile acid contents or compositions.
I next examined VDR activation by injecting LCA or vitamin D3 (VD3), the active form of vitamin D, to the wild type mice. VD3 activated VDR mainly in the proximal part of small intestine, while LCA activated VDR in the distal part of small intestine. My data suggest that VDR plays a role in maintenance of intestinal homeostasis in DIO mice via secondary bile acids.
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| Academic Significance and Societal Importance of the Research Achievements |
＜学術的意義＞VDR欠損マウスでは腸内細菌組成、胆汁酸組成が変化するが、これらは高脂肪食によるVDR欠損マウスの体重が増えないことへの関わりは弱かった。二次胆汁酸LCAが下部小腸選択的にVDRを活性化することは、近年報告されているLCAの免疫調節作用や大腸炎抑制作用を仲介するメカニズムの一つと考えられた。＜社会的意義＞高脂肪、高コレステロール状態に反応したLCAの排出量増加と、LCA依存性のVDR活性化部位を同定したことは、肥満等生活習慣病に伴う腸内環境の変化、免疫系の変化によって増加する全身性の疾患リスクに対して、これらを調節する機能を有するVDRを標的とした治療・健康維持戦略を提案できた。
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