The decreased thermogenic activity in brown fat during the development of obesity

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K19709
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: The University of Tokushima
• Principal Investigator: KURODA Masashi 徳島大学, 大学院医歯薬学研究部(医学域), 助教 (00803579)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 褐色脂肪細胞 / エネルギー代謝 / 熱産生 / 肥満 / メタボリックシンドローム

Outline of Final Research Achievements

Energy expenditure for thermogenesis in brown adipose tissue serves to maintain whole body energy homeostasis, but during the development of obesity, this thermogenic function is impaired. In this study, by combining DNA microarray analysis of brown fat, and the prediction of transcription factor binding analysis, we have identified the transcription factor, IRF7 (Interferon Reguratory Factor 7) as a possible suppressor for thermogenesis in brown fat.
IRF7 knockout mice showed increased expression of thermogenic genes in brown adipose and were more resistant to a cold enviroment than wild type control. Also, under high fat feeding condition, knockout mice showed improved adiposity and glucose tolerance. These data indicate that IRF7 is associated with the decreased thermogenic activity during the development of obesity.

Free Research Field

代謝栄養学

Academic Significance and Societal Importance of the Research Achievements

肥満形成における褐色脂肪機能不全については、褐色脂肪組織内での炎症や過剰な酸化・小胞体ストレスの関与が指摘されてきた。炎症や種々のストレスは肥満ともに進展し、熱産生低下の増悪因子であると考えらえるが、実際には炎症・ストレスマーカー遺伝子が誘導されない程度の短期間マウスへ高脂肪食を給餌した際にも、既に熱産生関連遺伝子の抑制が生じていることから根本的な原因とは考えにくい。本研究は肥満に関わる褐色脂肪機能不全について、より本質的なメカニズムを明らかにし、肥満予防・治療法の確立に向けた基礎知見の獲得を試みた。