Analysis of the mechanism of nuclear co-localization of Insulin Receptor beta-Subunit and transcription factors FoxK1/2 and their target genes

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K19511
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 54:Internal medicine of the bio-information integration and related fields
• Research Institution: Kumamoto University
• Principal Investigator: Araki Eiichi 熊本大学, 大学院生命科学研究部(医), 名誉教授 (10253733)
• Co-Investigator(Kenkyū-buntansha): 阪口 雅司 熊本大学, 大学院生命科学研究部(医), 助教 (90625774)
• Project Period (FY): 2021-07-09 – 2024-03-31
• Keywords: インスリンシグナル / 糖尿病 / 褐色脂肪組織 / ミトコンドリア

Outline of Final Research Achievements

It has been revealed that insulin signaling regulates the mitochondrial function of brown fat through a pathway mediated by the transcription factor FoxK1, which moves to the nucleus from the cytoplasm in response to insulin stimulation. This pathway, mediated by FoxK1 and its paralog FoxK2, exhibits behavior contrary to that of the transcription factor FoxO1, which is known to move from the nucleus to the cytoplasm through the conventional insulin signaling pathway. Therefore, it has been hypothesized and verified that this pathway could potentially serve as a therapeutic target for controlling energy expenditure in brown adipocytes and treating obesity.

Free Research Field

糖尿病・代謝内分泌学

Academic Significance and Societal Importance of the Research Achievements

本研究の成果より、FoxK1とFoxK2は褐色脂肪においてミトコンドリア機能を活性化し、エネルギー消費を制御することが明らかとなった。加齢や生活習慣よるインスリン抵抗性を基盤とした肥満症に対して、褐色脂肪組織制御の視点から肥満、2型糖尿病の予防、治療に結びつくものと期待される。