p62 in muscles inhibits obesity-related sarcopenia through a control of mitophagy

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K19694
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 59:Sports sciences, physical education, health sciences, and related fields
• Research Institution: University of Tsukuba
• Principal Investigator: Shoda Junichi 筑波大学, 医学医療系, 客員教授 (90241827)
• Co-Investigator(Kenkyū-buntansha): 鈴木 英雄 筑波大学, 医学医療系, 准教授 (00400672) ; 石井 亜紀子 筑波大学, 医学医療系, 講師 (10400681) ; 岡田 浩介 筑波大学, 医学医療系, 准教授 (80757526)
• Project Period (FY): 2021-07-09 – 2023-03-31
• Keywords: 肥満 / サルコペニア / サルコペニア肥満 / p62 / mitophagy / autophagy / 運動療法

Outline of Final Research Achievements

A maintenance of skeletal muscles in obese subjects is an important issue because of poor survival outcome of sarcopenic obesity. In this study, we aimed to determine the effects of muscle p62 on skeletal muscle mass and muscle strength. We generated muscle-specific p62 gene rescue mice (p62-mRes), which express p62 only in muscle and were derived from p62-knock out mice (p62KIKI) using the cre/loxp system. p62KIKI and p62-mRes mice were fed an HFD for 20 weeks. HFD-feeding caused severe obesity in both p62KIKI and p62-mRes mice, but there was no effect of muscle p62 on body mass. Limb skeletal muscle mass, grip strength, and the cross-sectional area of muscle fibers were higher in p62-mRes mice than in p62KIKI. The glucose tolerance and insulin sensitivity of the p62-mRes mice were also superior. The maintenance of skeletal muscle mass and function induced by p62 in muscle reduces insulin resistance in obese mice and protects against steatohepatitis via a muscle-liver axis.

Free Research Field

健康応用科学

Academic Significance and Societal Importance of the Research Achievements

サルコペニア肥満は，予後不良の疾病病態であるが，日常臨床の現場においてその対策は十分に機能しているとは言い難い．本研究では，筋のp62が肥満の病態下で，体組成には影響せず，骨格筋量・筋力の維持，インスリン抵抗性に対して防御的に機能することを見出した．これらの結果は，肥満者に対する筋p62を標的とした新たなサルコペニア予防・治療法の構築につながる可能性があり，大きな発展が期待される．