Regulatory mechanism of hepatic glucose metabolism by ghrelin and LEAP2

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08911
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: University of Miyazaki
• Principal Investigator: Sakoda Hideyuki 宮崎大学, 医学部, 准教授 (50376464)
• Co-Investigator(Kenkyū-buntansha): 張 維東 宮崎大学, 医学部, 助教 (90753616) ; イスラム エムデイーヌルル 宮崎大学, 医学部, 研究員 (10870149) ; 中里 雅光 宮崎大学, フロンティア科学総合研究センター, 特別教授 (10180267)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: ペプチド / 糖脂質代謝 / 臓器連関 / 肥満

Outline of Final Research Achievements

To Analyze the molecular mechanism by which the endogenous antagonist of ghrelin, LEAP2, regulates glucose and lipid metabolism in the liver, we examined LEAP2 in pathological conditions.
Human LEAP-2 in CSF was significantly increased in the patients with bacterial meningitis. In bacterial meningitis, LEAP-2 is produced locally in the brain and may be useful as a potential biomarker. Administration of LEAP2 to calorie-restricted mice induced inflammation and more weight loss in both C57BL/6 J mice or Ghsr-KO mice. Our findings suggest that LEAP2 functions independently of GHSR, implying that LEAP2 affects physiology beyond the ghrelin-GHSR system.

Free Research Field

糖脂質代謝

Academic Significance and Societal Importance of the Research Achievements

グレリンのアゴニストが癌カヘキシアの治療薬として実用化されている。LEAP2がグレリンを阻害する機序や病態における役割を解析して、グレリンとLEAP2による摂食やエネルギー代謝調節機構を明らかにすることで、新たな治療薬やバイオマーカーの開発に貢献できる可能性が示された。