Elucidation of the pathology of the diseases based on metabolic disorders

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08881
• 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: Keio University (2021-2022); The University of Tokyo (2020)
• Principal Investigator: Tanaka Hirotoshi 慶應義塾大学, 医学部(信濃町), 特別招聘教授 (00171794)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 骨格筋 / 肥満 / 糖尿病 / グルココルチコイド受容体 / グルココルチコイド / インスリン / 臓器連関 / 脂肪肝

Outline of Final Research Achievements

Fat accumulation in liver and adipose tissue, hyperglycemia, and hyperinsulinemia in the obesity model induced by chronic corticosterone (CORT) treatment or ob/ob mice improved in muscle-specific glucocorticoid receptor (GR)-knockout (GRmKO) mice. Muscle GR-mediated hyperinsulinemia was a critical factor for promoting fat accumulation in adipose tissue. This was in contrast to the regulator for body composition under physiological conditions, wherein the alanine-FGF21 axis is critical. In addition, the significance of muscle GR signaling in the pathophysiology of obesity showed sex differences. Thus, we provide insight into the treatment of obesity and diabetes under a conditionally determined pathway involving muscle GR signaling.

Free Research Field

エネルギー代謝

Academic Significance and Societal Importance of the Research Achievements

骨格筋GRシグナルへの介入は、肥満抑制のみならず、脂肪肝の軽減、筋萎縮防止、高インスリン血症の是正、高血糖の是正などを同時に実現できる可能性があることを示し、新規の治療標的機構を提示した。さらに、個体の条件によって代謝制御機構が変容すること、そのため疾患介入戦略も個体の状態に応じて調整する必要性があることも示唆した。