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Download fileCold-inducible Klf9 regulates thermogenesis of brown and beige fat
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posted on 2020-09-29, 19:24 authored by Ada AdminAda Admin, 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 ChangPromoting development and function of brown
and beige fat may represent an attractive treatment of obesity. In the present
study, we show that fat Klf9 expression is
markedly induced by cold exposure and a β-adrenergic
agonist. Moreover, Klf9 expression levels in human white adipose tissue (WAT)
are inversely correlated with adiposity, and Klf9 overexpression in
primary fat cells stimulates cellular thermogenesis, which is Ucp1-dependent. Fat-specific Klf9 transgenic mice gain
less weight and have smaller fat pads due to increased thermogenesis of brown
and beige fat. Moreover, Klf9 transgenic mice displayed lower fasting blood
glucose levels, improved glucose tolerance and insulin sensitivity under the
high-fat diet condition. Conversely, Klf9 mutation in brown adipocytes reduces the expression
of thermogenic genes, causing a reduction in cellular respiration. Klf9-mutant
mice exhibited obesity and cold sensitivity due to impairments in the
thermogenic function of fat. Finally, fat Klf9 deletion inhibits the β3-agonist-mediated
induction of WAT browning and
brown
adipose tissue thermogenesis. Mechanistically, Cold-inducible Klf9 stimulates expression of PGC-1α,
a master regulator of fat thermogenesis, by a direct binding to its gene
promoter region, subsequently promoting energy expenditure. The present study
reveals a critical role for Klf9 in mediating thermogenesis of brown and beige
fat.