Regulatory mechanism of beige adipocyte-differentiation by protein phosphatase.

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K17952
• 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: Tohoku University
• Principal Investigator: Ito Ryo 東北大学, 医学系研究科, 助教 (80733815)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 熱産生

Outline of Final Research Achievements

Beige adipocytes are attracting attention as a novel therapeutic target for lifestyle-related diseases because beige adipocyte burn sugar and fat actively. It has been shown that the histone demethylase JMJD1A is phosphorylated downstream of the β-adrenergic signal, removing the inhibitory histone methylation and activating chromatin. It was unclear how this phosphorylation level of JMJD1A was regulated. In this study, we comprehensively searched for JMJD1A interacting factors and identified a phospho JMJD1A protein phosphatase complex (p-JMJD1A-PPC). p-JMJD1A-PPC dephosphorylate phosphorylated JMJD1A and contributed to the regulation of the expression of thermogenic genes in beige adipocytes.

Free Research Field

遺伝子発現制御、分子代謝生理学

Academic Significance and Societal Importance of the Research Achievements

本研究では、ヒストン脱メチル化酵素JMJD1Aのリン酸化調節に着目し、脱リン酸化酵素を同定し、その脱リン酸化酵素を阻害することでJMJD1Aのリン酸化を亢進させ、ベージュ脂肪細胞分化を促進できることを明らかにした。すなわち、脱リン酸化酵素のコントロールを介してヒストン脱メチル化酵素による遺伝子発現を調節できることを示しており、この点に学術的意義がある。また、これらの成果は肥満や高脂血症といった生活習慣病に対する治療薬開発に貢献できると考えられる。