Cold-Inducible Klf9 Regulates Thermogenesis of Brown and Beige Fat

• DOI: 10.2337/db19-1153
• Publication Date: 2020-09-30T01:06:17Z
• Authors: Heng Fan; Yujie Zhang; Jun Zhang; Qiyuan Yao; Yongfeng Song; Qiwei Shen; Jun Lin; Yuanxu Gao; Xiuyun Wang; Lei Zhang; Yinliang Zhang; Pingsheng Liu; Jiajun Zhao; Qinghua Cui; John Zhong Li; Yongsheng Chang
• Keywords: Thermogenin

Promoting development and function of brown beige fat may represent an attractive treatment obesity. In the current study, we show that Klf9 expression is markedly induced by cold exposure a β-adrenergic agonist. Moreover, levels in human white adipose tissue (WAT) are inversely correlated with adiposity, overexpression primary cells stimulates cellular thermogenesis, which Ucp1 dependent. Fat-specific transgenic mice gain less weight have smaller pads due to increased thermogenesis fat. displayed lower fasting blood glucose improved tolerance insulin sensitivity under high-fat diet condition. Conversely, mutation adipocytes reduces thermogenic genes, causing reduction respiration. Klf9-mutant exhibited obesity impairments Finally, deletion inhibits β3 agonist-mediated induction WAT browning thermogenesis. Mechanistically, cold-inducible Pgc1α, master regulator direct binding its gene promoter region, subsequently promoting energy expenditure. The study reveals critical role for KLF9 mediating