Elucidation of the regulatory mechanism of cell function by the nutrition-metabolism-epigenome axis

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K21747
• 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: The University of Tokyo
• Principal Investigator: Sakai Juro 東京大学, 先端科学技術研究センター, 教授 (80323020)
• Project Period (FY): 2020-07-30 – 2023-03-31
• Keywords: エピゲノム / 代謝シグナル / 脂肪細胞 / 細胞運命決定 / 環境 / 栄養

Outline of Final Research Achievements

Elucidation of pathology and prevention of lifestyle-related diseases caused by obesity are major issues in medicine and health science. In this study, we aimed to elucidate the epigenetic mechanism by which adipocytes acquire the function of accumulating fat. We performed an integrated analysis of the metabolome, transcriptome, and epigenome during adipocyte differentiation under high and low glucose conditions. It was suggested that adipocytes metabolize extracellular glucose to α-ketoglutarate, which is sensed by histone demethylase, and rewrite the epigenome of glycolysis genes, thereby acquiring the function of converting glucose into fat and accumulating it. This study clarified a part of the regulatory mechanism of adipocyte function by the nutrition-metabolism-epigenome axis.

Free Research Field

代謝学、内分泌学、栄養学、エピジェネティクス

Academic Significance and Societal Importance of the Research Achievements

肥満に起因した生活習慣病の病態解明と予防は医学・健康科学の大きな課題であるが、脂肪細胞が糖を脂肪に変換して蓄積する機能を獲得するしくみは不明であった。本研究により栄養-代謝-エピゲノム軸による脂肪細胞機能調節の仕組みの一端がはじめて明らかとなった。本研究で得られた成果は、生活習慣病の効果的な予防・治療法につながることが期待される。