Epigenetic mechanisms of metabolic reprogramming under nutritional stress

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K07215
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical genome science
• Research Institution: Kumamoto University
• Principal Investigator: Hino Shinjiro 熊本大学, 発生医学研究所, 准教授 (00448523)
• Research Collaborator: ANAN Kotaro ; TAKASE Ryuta ; KOHROGI Kensaku ; ARAKI Hirotaka ; HINO Yuko
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: ヒストン脱メチル化 / 代謝リプログラミング / 筋線維型

Outline of Final Research Achievements

Skeletal muscle is composed of two different fiber types, fast- and slow-twitch fibers. While the fast is specialized for dynamic movements and glycolytic metabolism, the slow is specialized for endurance and show active mitochondrial respiration. Composition of these fiber types is highly influenced by environmental factors such as exercise and diet, and is associated with the risks of chronic diseases such as diabetes. This study was aimed at elucidating the mechanisms by which fiber types are determined under the influence of environmental factors. We found that a histone demethylase, LSD1, represses both slow fiber and respiration associated genes to promote fast fiber traits. In addition, we found that glucocorticoid, a hormone secreted in undernutrition state, promotes the degradation of LSD1 leading to the enhanced slow fiber formation. Our findings uncover the molecular mechanisms that link environment to muscle fiber, and would contribute to understanding chronic diseases.

Free Research Field

エピジェネティクス

Academic Significance and Societal Importance of the Research Achievements

本研究により、骨格筋の機械的性質とエネルギー代謝特性を連動させる遺伝子発現調節機構が明らかとなった。また、栄養環境が長期的な筋線維組成に反映される仕組みが明らかになった。これらの成果は、環境によって動物の体質が可塑的に変化する仕組みを理解する上で大きな手掛かりとなる。また、生活習慣病などの慢性疾患の発症機序解明に貢献できると考えられ、予防法や治療法の開発に資する。