Glucose regulation of adipose tissue browning by CBP/p300-and HDAC3-mediated reversible acetylation of CREBZF

• 成果类型: Article
• 署名作者: Cui, Aoyuan; Xue, Yaqian; Su, Weitong; Lin, Jing; Liu, Yuxiao; Cai, Genxiang; Wan, Qin; Jiang, Yang; Ding, Dong; Zheng, Zengpeng; Wei, Shuang; Li, Wenjing; Shen, Jiaxin; Wen, Jian; Huang, Mengyao; Zhao, Jiuxiang; Zhang, Xiaojie; Zhao, Yuwu; Li, Hong; Ying, Hao; Zhang, Haibing; Bi, Yan; Chen, Yan; Xu, Aimin; Xu, Yong; Li, Yu
• 署名单位: Chinese Academy of Sciences; University of Chinese Academy of Sciences, CAS; Shanghai Institute of Nutrition & Health, CAS; Southwest Medical University; Tianjin University of Science & Technology; Southwest Medical University; Chinese Academy of Sciences; Shanghai Institute of Nutrition & Health, CAS; Shanghai Jiao Tong University; Chinese Academy of Sciences; Shanghai Institute of Nutrition & Health, CAS; Nanjing University; University of Hong Kong; University of Hong Kong; University of Hong Kong
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-11875
• DOI: 10.1073/pnas.2318935121
• 发表日期: 2024-04-16
• 关键词: pgc-1-alpha; white; coactivator; mechanisms; cell

摘要

Glucose is required for generating heat during cold- induced nonshivering thermogenesis in adipose tissue, but the regulatory mechanism is largely unknown. CREBZF has emerged as a critical mechanism for metabolic dysfunction- associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD). We investigated the roles of CREBZF in the control of thermogenesis and energy metabolism. Glucose induces CREBZF in human white adipose tissue (WAT) and inguinal WAT (iWAT) in mice. Lys208 acetylation modulated by transacetylase CREB- binding protein/p300 and deacetylase HDAC3 is required for glucose- induced reduction of proteasomal degradation and augmentation of protein stability of CREBZF. Glucose induces rectal temperature and thermogenesis in white adipose of control mice, which is further potentiated in adipose- specific CREBZF knockout (CREBZF FKO) mice. During cold exposure, CREBZF FKO mice display enhanced thermogenic gene expression, browning of iWAT, and adaptive thermogenesis. CREBZF associates with PGC- 1 alpha to repress thermogenic gene expression. Expression levels of CREBZF are negatively correlated with UCP1 in human adipose tissues and increased in WAT of obese ob/ob mice, which may underscore the potential role of CREBZF in the development of compromised thermogenic capability under hyperglycemic conditions. Our results reveal an important mechanism of glucose sensing and thermogenic inactivation through reversible acetylation.