Development of obesity treatment methods focusing on the regulatory mechanism of adipose tissue ChREBP expression by GIP

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K19673
• 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: Gifu University
• Principal Investigator: LIU YANYAN 岐阜大学, 大学院医学系研究科, 研究員 (10845796)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: Chrebp / incretin

Outline of Final Research Achievements

The glucose-activating transcription factor carbohydrate response element-binding protein (ChREBP) is a transcription factor that regulates adipose synthesis gene expression. ChREBP activity in adipose tissue decreases with the progression of obesity, resulting in reduced glucose disposal capacity, but the regulatory mechanism of ChREBP activity in adipose tissue is still unknown. In the present study, we showed the effect of the gastrointestinal hormone glucose-dependent insulinotropic polypeptide (GIP), that increases in the obese state, may cause a decrease in ChREBP activity in adipose tissue.

Free Research Field

代謝

Academic Significance and Societal Importance of the Research Achievements

ヒトの脂肪組織におけるChREBPはインスリン感受性を予測し、脂肪組織特異的ChREBP欠損マウスはインスリン感受性が低下することが報告された。したがって、脂肪組織でのChREBP活性を高めることで脂肪組織のインスリン感受性を改善できる可能性がある。しかるに、脂肪細胞におけるChREBP活性の制御機構はこれまで不明であり、わずかにホルモン感受性リパーゼとの相互作用が知られているが、脂肪組織特異的にChREBP活性を高める薬剤は現在存在しない。肥満の進展の際に、脂
肪組織におけるChREBPの低下メカニズムを解明すれば、新規肥満予防法の開発が期待できる。