Foxp1 controls brown/beige adipocyte differentiation and thermogenesis through regulating β3-AR desensitization

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 () and Xizhi Guo ()
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Pei Liu: Shanghai Jiao Tong University Affiliated Sixth People’s Hospital
Sixia Huang: Ministry of Education, Shanghai Jiao Tong University
Shifeng Ling: Ministry of Education, Shanghai Jiao Tong University
Shuqin Xu: Ministry of Education, Shanghai Jiao Tong University
Fuhua Wang: Ministry of Education, Shanghai Jiao Tong University
Wei Zhang: Ministry of Education, Shanghai Jiao Tong University
Rujiang Zhou: Ministry of Education, Shanghai Jiao Tong University
Lin He: Ministry of Education, Shanghai Jiao Tong University
Xuechun Xia: Ministry of Education, Shanghai Jiao Tong University
Zhengju Yao: Ministry of Education, Shanghai Jiao Tong University
Ying Fan: Shanghai Jiao Tong University Affiliated Sixth People’s Hospital
Niansong Wang: Shanghai Jiao Tong University Affiliated Sixth People’s Hospital
Congxia Hu: Shanghai Jiao Tong University
Xiaodong Zhao: Shanghai Jiao Tong University
Haley O. Tucker: University of Texas at Austin
Jiqiu Wang: Shanghai Jiao Tong University School of Medicine
Xizhi Guo: Shanghai Jiao Tong University Affiliated Sixth People’s Hospital

Nature Communications, 2019, vol. 10, issue 1, 1-12

Abstract: Abstract 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.

Date: 2019
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DOI: 10.1038/s41467-019-12988-8

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