Elucidatiaon of the role of KAT2A in the regualtion of energy metabolism

2017 Fiscal Year Final Research Report

• Project/Area Number: 15H04851
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Metabolomics
• Research Institution: National Center for Global Health and Medicine
• Principal Investigator: MATSUMOTO MICHIHIRO 国立研究開発法人国立国際医療研究センター, 研究所 糖尿病研究センター 分子代謝制御研究部, 部長 (90467663)
• Co-Investigator(Renkei-kenkyūsha): KIDO Yoshiaki 神戸大学, 大学院・保健学研究科, 教授 (10335440) ; INOUE Hiroshi 金沢大学, 新学術創成研究機構, 教授 (50397832)
• Research Collaborator: SAKAI Mashito ; MITSUSHIMA Masaru ; NAGANUMA Takao ; YANO Hiroyuki ; YAGI Takashi ; MATSUKAWA Toshiya
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 代謝調節 / 転写 / 酵素 / エピゲノム修飾 / 肥満 / 糖尿病 / 肝臓 / 脂肪組織

Outline of Final Research Achievements

The role of KAT2A in hepatocytes was investigated in the regulation of fasting metabolism using loss-of-function approaches in vivo and in vitro. In the fasted state, hepatic KAT2A formed a signalling module with transcriptional coregulator CITED2 and PKA promoted transcription of fasting response genes, and thereby adapted to fasting. Mechanistically, KAT2A was phosphorylated by PKA within the module, switched its substrate from transcriptional coactivator PGC-1α to histone H3, and thereby promoted activation of this coactivator and epigenomic changes in the promoter, resulting in activation of such gene transcription. These results suggest that KAT2A is a cAMP-responsible acetyltransferase that is critical to integrate fasting metabolic response in hepatocytes.

Free Research Field

糖尿病・代謝学