The functions of TFG in adipocytes, small intestine and hepatocytes and its involvement in metabolic disorders

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K17986
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Hiroshima University
• Principal Investigator: Yamamotoya Takeshi 広島大学, 医系科学研究科(医), 助教 (50760013)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 糖尿病 / 脂肪細胞 / 脂肪肝

Outline of Final Research Achievements

The abundance of Trk-fused gene (TFG) in white adipose tissues drastically increases in obesity. In adipocyte-specific TFG knockout mice, adipocyte dysfunction was apparent judging from downregulation of PPARγ activity in adipocytes and subsequent hepatic steatosis. However, short-term TFG deletion in culture cells or in primary adipocytes derived from adipose tissue stromal vascular fraction (SVF) did not result in PPARγ downregulation, which led us consider that the significance of TFG in adipocyte was cell-size dependent. Moreover, we found that hepatocyte-specific TFG knockout mice also displayed hepatic steatosis, which seemed attributable to insufficient induction of PPARα target genes during fasting.

Free Research Field

糖尿病

Academic Significance and Societal Importance of the Research Achievements

過剰な摂取エネルギーを適切に脂肪細胞に蓄えることは、脂肪肝などインスリン抵抗性の原因となる異所性脂肪蓄積を防ぎ、糖尿病の発症を抑えるために重要である。生体における脂肪細胞の適切な肥大に脂肪細胞のTFGが不可欠であること、また脂肪肝の抑制に肝細胞のTFGが重要であることが本研究で明らかとなった。その詳細なメカニズムについては現在検討中であるが、将来的に糖尿病や脂肪肝に対する新規治療薬の開発に繋がる可能性が期待できる。