Correlation between epigenetic control and GPCR focusing on feeding disorders

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K20143
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: Gifu University
• Principal Investigator: Hamamoto Akie 岐阜大学, 工学部, 助教 (60784197)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: Gタンパク質共役型受容体 / ヒストン脱アセチル化酵素 / メラニン凝集ホルモン受容体 / 摂食障害

Outline of Final Research Achievements

Although associated with eating disorders is predicted, the relationship between eating-related G protein-coupled receptors (GPCRs) and histone deacetylases (HDACs) has been completely unknown. Therefore, we focused on the melanin-concentrating hormone receptor (MCHR1), which is an orexigenic GPCR, and analyzed its relationship with HDAC. As a result, the correlation between MCHR1 and HDAC was clarified, and in particular, the involvement of HDAC5, 9 and 10 was shown. Focusing on HDAC10, which is presumed to be co-localized in the brain, the expression decreased and the localization changed due to MCH stimulation. Furthermore, we obtained an interesting result that HDAC10 selectively regulates the Gq pathway in MCHR1-mediated signaling system. It could be a new molecular mechanism for feeding-related GPCRs and epigenetics.

Free Research Field

生化学

Academic Significance and Societal Importance of the Research Achievements

摂食障害は生命を脅かすリスクのある深刻な疾患であるが、その制御機構はいまだ不明確である。摂食におけるエピジェネティクスの関与について、DNAメチル化に関する研究は多数報告されいるが、摂食関連GPCRとHDACの報告はほぼ存在しない。本研究は摂食行動に重要な役割を担うMCHR1に着目し、HDACと相関関係を有しており、お互い発現やシグナル制御に影響を及ぼすことを初めて明らかにした。本研究により摂食関連GPCRとエピジェネティクスの新たな分子機構が解明され、肥満・摂食障害などの新規治療戦略が期待される。