Elucidation of feeding mechanism and development of treatment method

• Project/Area Number: 18K08027
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Kojima Toshiya 東京大学, 医学部附属病院, 助教 (30625588)
• Co-Investigator(Kenkyū-buntansha): 藤生 克仁 東京大学, 医学部附属病院, 特任准教授 (30422306)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 転写因子KLF5 / 摂食調節 / AgRP / KLF5

Outline of Final Research Achievements

Increasing prevalence of obesity is an urgent public health challenge. The arcuate nucleus of the hypothalamus functions as a feeding center. The transcription factor Kruppel-like factor 5 (KLF5) is present in the arcuate nucleus of the hypothalamus. KLF5 suppresses Agrp activation by antagonizing AMPK and FoxO1, suggesting that KLF5 is a key factor connecting AMPK, FoxO1 and Agrp. KLF5 is essential for suppressing AgRP activity (appetite suppression). It was clarified that KLF5 is involved in feeding regulation and contributes to metabolic regulation in many ways.

Academic Significance and Societal Importance of the Research Achievements

肥満は臓器機能障害を引き起こし、心血管疾患の重要なリスクとなる。肥満の原因として過食を始めとする摂食調節の機序解明は重要である。摂食は視床下部弓状核で調節されている。転写因子Kruppel-like factor 5(KLF5)が視床下部弓状核に存在し、摂食調節に関与することで、多面的に代謝制御に寄与することを明らかとした。有効な予防・治療法の確率につながる知見であると考える。