| Project/Area Number |
17K16153
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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 |
Metabolomics
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| Research Institution | Jichi Medical University |
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Principal Investigator |
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| Research Collaborator |
Leibel Rudolph Columbia University, Department of Pediatrics, Professor
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 脂肪肝 / ILDR2 / リン脂質 / 糖尿病 / ERストレス |
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| Outline of Final Research Achievements |
Non-alcoholic fatty liver disease (NAFLD) is associated with obesity and type 2 diabetes and increases the risk for liver cirrhosis and cancer. A diabetes susceptibility gene, Ildr2, encodes a transmembrane protein localized to the ER membrane whose physiological functions are unknown. We previously identified ILDR2 interaction protein, MBOAT7, which mediates acyl-chain remodeling of phosphatidylinositols (PIs). We hypothesized that ILDR2 may influence hepatic Pl composition in NAFLD. In LKO-ILDR2 mice fed on the MCD diet compared to AAV-GFP injected Ildr2 floxed (GFP-flox) mice fed on the MCD diet, liver triglyceride content was significantly increased by 1.6-foldIn LKO-ILDR2 mice compared to GFP-flox mice, hepatic PI was significantly increased. Manipulation of hepatic ILDR2 expression is associated with changes in PI molecular species in the liver.
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| Academic Significance and Societal Importance of the Research Achievements |
我々はILDR2の機能に関して、局在や結合タンパク質の同定、さらにノックアウトマウスを解析することによりその個体レベルでの意義を明らかにした。この研究過程で、ILDR2が肝臓中リン脂質の質的変化に関与し、脂肪肝発症に関与することが示唆された。脂肪肝の直接の治療法はないため、ILDR2の機能解明は脂肪肝の治療法開発の分子基盤になると期待される。
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