2016 Fiscal Year Final Research Report
Analysis of regulation of lipid metabolism by vitamin D metabolite
| Project/Area Number |
26350972
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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 |
Chemical biology
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| Research Institution | Hokkaido University (2015-2016)
Kyoto University (2014) |
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Principal Investigator |
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Keywords | ビタミンD / 脂質代謝 |
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| Outline of Final Research Achievements |
This study revealed that an endogenous vitamin D metabolite suppresses the lipid biosynthesis. Sterol regulatory element-binding proteins (SREBPs) are transcription factors that control lipid homeostasis. We screened a chemical library of endogenous molecules and identified 25-hydroxyvitamin D (25OHD) as an inhibitor of SREBP activation. Unlike sterols and other SREBP inhibitors, 25OHD impairs SREBP activation by inducing proteolytic processing and ubiquitin-mediated degradation of SCAP, thereby decreasing SREBP levels independently of the vitamin D receptor. Vitamin D supplementation has been proposed to reduce the risk of metabolic diseases, but the mechanisms are unknown. The present results suggest a previously unrecognized molecular mechanism of vitamin D-mediated lipid control that might be useful in the treatment of metabolic diseases.
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| Free Research Field |
ケミカルバイオロジー
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