Metabolome analysis to clarify mitochondrial activation by a metabolism-epigenome link induced by intermittent fasting

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17500
• 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: Keio University
• Principal Investigator: Endo Sho 慶應義塾大学, 医学部(信濃町), 共同研究員 (20772354)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 間欠絶食 / 肥満 / 糖尿病 / 耐糖能 / 運動耐容能 / ヒストンアセチル化 / 脂肪燃焼 / ミトコンドリア

Outline of Final Research Achievements

To explore the mechanism by which intermittent fasting (IF) exerts prolonged effects after discontinuation, we examined mice that had been subjected to 4 cycles of fasting for 72 hours and ad libitum feeding for 96 hours per week (72hIF), focusing on expression of genes for lipid metabolism in the skeletal muscle and histone acetylation in the promoter region. 72hIF resulted in metabolic remodeling, characterized by enhanced lipid utilization and mitochondrial activation in the muscle. Sustainable promotion of histone acetylation in lipid oxidation genes of the muscle and adipose tissues during and after IF may contribute to sustained metabolic effects of IF.

Free Research Field

臨床代謝内分泌学を背景とした間欠絶食などの新しい食事療法の開発

Academic Significance and Societal Importance of the Research Achievements

本研究の結果は, 間欠絶食中止後も持続する代謝効果のメカニズムを示しており, 肥満糖尿病患者での長期減量効果やインスリン抵抗性の改善に応用できる可能性がある. すなわち、間欠絶食にて脂肪燃焼遺伝子群のヒストンアセチル化に長期の変化が生じることは, 遺伝子発現の変化ならびに減量・インスリン抵抗性改善効果が長期にわたり持続する可能性を示唆する. マウスによる本研究成果の, 肥満糖尿病患者への応用可能性につき, 今後の研究を展開できれば幸いである.