The molecular mechanism underlying the activation of brown adipocytes

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K08667
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Iwate Medical University
• Principal Investigator: Hasegawa Yutaka 岩手医科大学, 医学部, 特任講師 (90451559)
• 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)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 褐色/ベージュ脂肪細胞 / インスリン抵抗性 / 線維化

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.

Free Research Field

糖尿病、肥満

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。