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β-Adrenergic receptor (β-AR) signaling is a pathway controlling adaptive thermogenesis in brown or beige adipocytes. Here we investigate the biological roles of the transcription factor Foxp1 in brown/beige adipocyte differentiation and thermogenesis. Adipose-specific deletion of Foxp1 leads to an increase of brown adipose activity and browning program of white adipose tissues. The Foxp1-deficient mice show an augmented energy expenditure and are protected from diet-induced obesity and insulin resistance. Consistently, overexpression of Foxp1 in adipocytes impairs adaptive thermogenesis and promotes diet-induced obesity. A robust change in abundance of the β3-adrenergic receptor (β3-AR) is observed in brown/beige adipocytes from both lines of mice. Molecularly, Foxp1 directly represses β3-AR transcription and regulates its desensitization behavior. Taken together, our findings reveal Foxp1 as a master transcriptional repressor of brown/beige adipocyte differentiation and thermogenesis, and provide an important clue for its targeting and treatment of obesity.


Pei Liu, Sixia Huang, Shifeng Ling, Shuqin Xu, Fuhua Wang, Wei Zhang, Rujiang Zhou, Lin He, Xuechun Xia, Zhengju Yao, Ying Fan, Niansong Wang, Congxia Hu, Xiaodong Zhao, Haley O Tucker, Jiqiu Wang, Xizhi Guo. Foxp1 controls brown/beige adipocyte differentiation and thermogenesis through regulating β3-AR desensitization. Nature communications. 2019 Nov 07;10(1):5070

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PMID: 31699980

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