Elucidation of Gene Expression Regulatory Networks in Skeletal Muscle Metabolism: Toward the Creation of Exercise Mimetic Drugs

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K17509
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Ehime University (2022-2023); Kyoto University (2020-2021)
• Principal Investigator: Hosokawa Motoyasu 愛媛大学, 医学系研究科, 助教 (60812683)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 骨格筋代謝 / 筋量制御 / 高脂肪食 / トランスクリプトーム比較 / 運動模倣 / RNA結合タンパク質 / 遺伝子発現制御

Outline of Final Research Achievements

The purpose of this study was to comprehensively reveal the mechanisms of metabolic activation in skeletal muscle at the transcriptional and post-transcriptional regulatory levels in order to identify the targets of safer exercise-mimetic drugs. For this purpose, RNA-seq data were obtained from skeletal muscle of age-matched mice that had undergone metabolic changes by three different stimuli: 1. exercise, 2. ambient temperature change, 3. high-fat diet, and high-fat diet fed not only to wild-type mice but also to skeletal muscle-specific Sfpq-KO mice with metabolic abnormalities and decreased muscle mass. Transcriptome comparative analysis for these data led to establish a model analysis system to search for targets of exercise-mimetic drugs, and identify several candidate pathways of metabolic activation.

Free Research Field

骨格筋RNA制御学

Academic Significance and Societal Importance of the Research Achievements

本研究で明らかにされたことや、確立した筋代謝活性化-筋量変化解析のモデル系はより安全な運動模倣薬の標的探しに有用である。運動模倣の実現により骨格筋代謝を人為的に活性化することが可能になれば、肥満や糖尿病などの生活習慣病の治療・予防薬の開発、さらには加齢に伴う筋力・筋量の低下（サルコペニア）や筋量減少を伴う各種疾患でも筋代謝の異常が問題視されているので、それらの治療や予防にもつながることが期待される。