Elucidation of the molecular mechanism for triacylglycerol storage in white adipocytes and the mechanism of fatty liver and type 2 diabetes due to its disruption

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K06665
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 44010:Cell biology-related
• Research Institution: Osaka Prefecture University
• Principal Investigator: Takenaka Nobuyuki 大阪府立大学, 理学(系)研究科(研究院), 准教授 (20610504)
• Co-Investigator(Kenkyū-buntansha): 佐藤 孝哉 大阪府立大学, 理学(系)研究科(研究院), 教授 (20251655)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: Rac1 / 白色脂肪細胞 / インスリン / 脂肪酸 / 脂肪肝 / 糖尿病

Outline of Final Research Achievements

Insulin is a hormone that reduces the blood glucose and free fatty acid (FFA) level by stimulating glucose uptake in white adipose tissue. Impaired insulin signaling in white adipocytes cause hepatic steatosis. However, the molecular mechanisms for FFA uptake and hepatic steatosis remain incompletely understood. We have recently demonstrated that the Rho family small GTPase Rac1 plays an important role downstream of Akt2 in insulin-stimulated glucose uptake in white adipocytes. However, it remains unclear whether Rac1 is involved in insulin-stimulated FFA uptake. In this study, we aimed to clarify the involvement of Rac1 in insulin-stimulated FFA uptake and pathogenesis of hepatic steatosis by using adipo-rac1-KO mice. We found that Rac1 was implicated in insulin-dependent FFA uptake in white adipocytes. Furthermore, we identified a deficiency of Rac1 promotes inflammation in white adipose tissue, which leads to hepatic steatosis.

Free Research Field

細胞内シグナル伝達

Academic Significance and Societal Importance of the Research Achievements

本研究では、脂肪酸輸送担体CD36の細胞内動態イメージング法を世界で初めて開発し、この手法とマウス白色脂肪組織を用いた解析から、Rac1を介した新たな脂肪酸取り込み機構を明らかにした。本研究成果は、白色脂肪細胞での脂肪蓄積を制御する分子機構の新たな生物学的知見だけではなく、脂肪蓄積異常による脂肪肝や2型糖尿病の発症メカニズムの解明につながると考えられる。