Uncovering the Pathogenesis of Selective Insulin Resistance through FoxO1 and PPARA Regulation

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K16422
• 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: Chiba University
• Principal Investigator: Kitamoto Takumi 千葉大学, 医学部附属病院, 助教 (90916173)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: 糖尿病 / 脂質異常症 / インスリン抵抗性 / 肥満 / FoxO1 / PPARA

Outline of Final Research Achievements

In this study, the transcription factors FoxO1 and PPARα synergistically suppress hepatic glycogenesis and enhance insulin sensitivity. Luciferase assays using the G6pc gene showed that both transcription factors synergistically regulate glyconeogenesis in the presence of cAMP/Dex. Co-immunoprecipitation confirmed that both transcription factors do not bind directly to each other, suggesting that they bind individually to the same binding region. Experiments using hepatocyte-specific FoxO1/PPARα knockout mice showed that both transcription factors synergistically suppress glucose metabolism even under insulin resistance.

Free Research Field

代謝および内分泌学

Academic Significance and Societal Importance of the Research Achievements

本研究は、糖代謝とインスリン感受性の制御におけるFoxO1とPPARαの相乗効果を初めて明らかにし、糖尿病治療の新たな分子標的を示唆する。この成果は、選択的インスリン抵抗性のメカニズム解明に寄与し、糖尿病治療法の開発における重要な一歩となる可能性がある。また、インスリン感受性の改善に向けた新たなアプローチを提供し、社会的に糖尿病患者のQOL向上に貢献することが期待される。