Original Article

DDB1 prepares brown adipocytes for cold-induced thermogenesis

  • Xu Wang 1,2 ,
  • Shen-Ying Liu 1 ,
  • Guo-Sheng Hu 3 ,
  • Hao-Yan Wang 4 ,
  • Guo-Liang Zhang 4 ,
  • Xiang Cen 4 ,
  • Si-Ting Xiang 1 ,
  • Wen Liu 3 ,
  • Peng Li 1,2,5 ,
  • Haobin Ye 1 ,
  • Tong-Jin Zhao , 1,2
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  • 1. State Key Laboratory of Genetic Engineering, Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Zhongshan Hospital, Fudan University, Shanghai, China
  • 2. Shanghai Qi Zhi Institute, Shanghai, China
  • 3. School of Pharmaceutical Sciences, Fujian Provincial Key Laboratory of Innovative Drug Target Research, Xiamen University, Xiamen, Fujian, China
  • 4. State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian, China
  • 5. State Key Laboratory of Membrane Biology and Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China

Received date: 01 Jan 2022

Revised date: 17 Jan 2022

Accepted date: 18 Jan 2022

Copyright

2022 The Author(s) 2022. Published by Oxford University Press on behalf of Higher Education Press.

Abstract

Brown adipose tissue (BAT) plays a key role in thermogenesis during acute cold exposure. However, it remains unclear how BAT is prepared to rapidly turn on thermogenic genes. Here, we show that damage-specific DNA binding protein 1 (DDB1) mediates the rapid transcription of thermogenic genes upon acute cold exposure. Adipose- or BAT-specific Ddb1 knockout mice show severely whitened BAT and significantly decreased expression of thermogenic genes. These mice develop hypothermia when subjected to acute cold exposure at 4 ℃ and partial lipodystrophy on a high-fat diet due to deficiency in fatty acid oxidation. Mechanistically, DDB1 binds the promoters of Ucp1 and Ppargc1a and recruits positive transcriptional elongation factor b (P-TEFb) to release promoter-proximally paused RNA polymerase II (Pol II), thereby enabling rapid and synchronized transcription of thermogenic genes upon acute cold exposure. Our findings have thus provided a regulatory mechanism of how BAT is prepared to respond to acute cold challenge.

Cite this article

Xu Wang , Shen-Ying Liu , Guo-Sheng Hu , Hao-Yan Wang , Guo-Liang Zhang , Xiang Cen , Si-Ting Xiang , Wen Liu , Peng Li , Haobin Ye , Tong-Jin Zhao . DDB1 prepares brown adipocytes for cold-induced thermogenesis[J]. Life Metabolism, 2022 , 1(1) : 39 -53 . DOI: 10.1093/lifemeta/loac003

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