2021 Fiscal Year Final Research Report

Elucidation of lifestyle-related diseases development due to environmental factors and epigenetic memory

Research Project

PDF

Project/Area Number	16H06390
Research Category	Grant-in-Aid for Scientific Research (S)
Allocation Type	Single-year Grants
Research Field	Metabolomics
Research Institution	Tohoku University (2017-2021) The University of Tokyo (2016)
Principal Investigator	SAKAI Juro 東北大学, 医学系研究科, 教授 (80323020)
Co-Investigator(Kenkyū-buntansha)	松村欣宏東京大学, 先端科学技術研究センター, 准教授 (20375257) 川村猛東京大学, アイソトープ総合センター, 准教授 (70306835)
Project Period (FY)	2016-05-31 – 2021-03-31
Keywords	肥満 / 生活習慣病 / 脂肪細胞 / エピゲノム / 翻訳後修飾 / 適応熱産生
Outline of Final Research Achievements	Adipose tissue plays an important role in the development of obesity and lifestyle-related diseases. Adipose tissue plays a major role in the adaptation of individuals to their living environment: white adipocytes store fat and become hypertrophied under nutritional surpluses, while they turn browning and develop heat-producing capacity in cold environments. Failure of this adaptation can lead to lifestyle-related diseases. Epigenomics is a mechanism to control gene expression by chemical modification of histones and DNA. We have elucidated a stepwise mechanism by which epigenomic modification enzymes undergo post-translational modification in response to environmental stimuli to form specific protein complexes (1st step) and continuously induce heat-producing gene expression via histone demethylation (2nd step) to adapt to cold environment. We also demonstrated the possibility of targeting this mechanism for the treatment of lifestyle-related diseases.
Free Research Field	内分泌・代謝学
Academic Significance and Societal Importance of the Research Achievements	2型糖尿病を始め、肥満に起因した生活習慣病の発症進展に脂肪組織は重要な役割を持つ。脂肪組織は個体がおかれた環境に応じて動的に量と質を変化させる。余剰な栄養環境下では白色脂肪細胞は脂肪として蓄え肥大化する一方、寒冷刺激下で脂肪を燃焼する熱を産生する脂肪細胞が脂肪組織に集簇してくるなど、個体の生活環境の適応に大きく関与する。この適応がうまくなされないと生活習慣病の原因となる。本研究では脂肪細胞の質を制御する環境を感知するエピゲノム酵素がどのようにして細胞運命を決定するのかを解明し、新規治療標的の可能性を提示した。