Mechanisms of brown fat differentiation through chromatin modification

2018 Fiscal Year Final Research Report

• Project/Area Number: 16H06226
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Pathological medical chemistry
• Research Institution: Hiroshima University
• Principal Investigator: Ohno Haruya 広島大学, 医歯薬保健学研究科(医), 助教 (60725894)
• Research Collaborator: Nagano Gaku ; Morita Yoshimi ; Egusa Gentaro
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 褐色脂肪細胞 / ベージュ脂肪細胞

Outline of Final Research Achievements

The purpose of this study is to explore and analyze a new epigenetic factor that can modulate differentiation and function of brown adipocytes and beige adipocytes. We identified methionine adenosyltransferase II α(MATIIα), a synthetase of methyl donor S-adenosylmethionine, as a newly binding partner of a PRDM16/EHMT1 transcriptional complex. Genetic ablation of MATIIαcauses a loss of brown adipose tissue in vivo. Depletion of MATIIα in brown adipocytes or beige adipocytes induced demethylation of H3K9 at a promoter region of white adipocyte specific genes and caused reductions of thermogenic genes such as ucp1. These findings revealed a novel mechanism that MATIIα modulate differentiation of brown adipocytes through chromatin modification.

Free Research Field

糖尿病

Academic Significance and Societal Importance of the Research Achievements

本研究によりMATIIαがエピジェネティック調節機構を介して褐色脂肪細胞およびベージュ脂肪細胞の分化調節を行っているだけでなく、クレアチン生合成を介したUCP1非依存的な熱産性能をも制御しているという多面的な機能が明らかとなった．褐色脂肪細胞やベージュ脂肪細胞はエネルギーを熱として散逸させることができ，肥満症や糖尿病治療への応用が期待されている．今後MATIIαを含む転写複合体の機能解析を通じて褐色脂肪細胞やベージュ脂肪細胞の分化を促進させることや，UCP1に依存しない熱産生能を活性化させることができれば，糖尿病や肥満症治療の新たな選択肢を提示することができると期待される．