| Project/Area Number |
17K08667
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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 |
Pathological medical chemistry
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| Research Institution | Iwate Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
武部 典子 岩手医科大学, 医学部, 講師 (30398474)
石垣 泰 岩手医科大学, 医学部, 教授 (50375002)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 褐色/ベージュ脂肪細胞 / インスリン抵抗性 / 線維化 / メタボリック症候群 / 褐色脂肪細胞 / 肥満 / Fibrosis / 熱産生 / 糖尿病 / 生理学 / 生体分子 |
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| Outline of Final Research Achievements |
By biochemically purifying the PRDM16 complex, we identified GTF2IRD1, as a cold-inducible transcription factor that mediates to suppress fibrosis via direct interaction. Adipocyte-selective expression of GTF2IRD1 suppresses adipose tissue fibrosis and improves systemic glucose homeostasis, while depleting GTF2IRD1 promotes fibrosis in a cell-autonomous manner. GTF2IRD1 suppresses the expressions of TGF-β-dependent pro-fibrosis genes. These results suggest a mechanism by which a PRDM16 complex alleviates diet-induced adipose tissue fibrosis, thereby improving systemic insulin resistance and glucose homeostasis. Furthermore, GTF2IRD1 forming a complex with PRDM16, mediates the suppression of TGF-β related pro-fibrosis genes independently of UCP1. Our data provide a novel insight into approaches to improving systemic insulin resistance and glucose homeostasis by targeting adipose tissue fibrosis.
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| Academic Significance and Societal Importance of the Research Achievements |
褐色/ベージュ脂肪細胞は、熱産生機構を備える脂肪細胞である。褐色/ベージュ脂肪細胞は、肥満や全身の糖代謝を改善させる機構があるため重要な治療ターゲットとして注目されている。今回、この褐色/ベージュ脂肪細胞に強く発現している転写因子GTF2IRD1を同定できた。この転写因子は、線維化を抑制し、糖代謝を改善する機構があることを明らかにした。
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