2. Academic Validation
  3. Reduced hepatic bradykinin degradation accounts for cold-induced BAT thermogenesis and WAT browning in male mice

Reduced hepatic bradykinin degradation accounts for cold-induced BAT thermogenesis and WAT browning in male mice

  • Nat Commun. 2023 May 2;14(1):2523. doi: 10.1038/s41467-023-38141-0.
Fei Xiao # 1,  Haizhou Jiang # 2,  Zi Li 2,  Xiaoxue Jiang 1,  Shanghai Chen 1,  Yuguo Niu 1,  Hanrui Yin 2,  Yousheng Shu 1,  Bo Peng 1,  Wei Lu 1,  Xiaoying Li 1,  Zhigang Li 2,  Shujue Lan 3,  Xiaoyan Xu 4,  Feifan Guo 5
Affiliations

Affiliations

  • 1 Zhongshan Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Fudan University, Shanghai, China.
  • 2 CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
  • 3 Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, China.
  • 4 Core Facility Center, CAS Center for Excellence in Molecular Plant Sciences, Chinese Academy of Sciences, Shanghai, China.
  • 5 Zhongshan Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Fudan University, Shanghai, China. ffguo@fudan.edu.cn.
  • # Contributed equally.
PMID: 37130842 DOI: 10.1038/s41467-023-38141-0
Abstract

An important role for liver in the regulation of adipose tissue thermogenesis upon cold exposure has been suggested; however, the underlying mechanisms remain incompletely defined. Here, we identify elevated serum bradykinin levels in response to acute cold exposure in male mice. A bolus of anti-bradykinin Antibodies reduces body temperature during acute cold exposure, whereas bradykinin has the opposite effect. We demonstrate that bradykinin induces brown adipose tissue thermogenesis and white adipose tissue browning, and bradykinin increases uncoupling protein 1 (UCP1) expression in adipose tissue. The bradykinin B2 receptor (B2R), adrenergic signaling and nitric oxide signaling are involved in regulating bradykinin-increased UCP1 expression. Moreover, acute cold exposure inhibits hepatic prolyl endopeptidase (PREP) activity, causing reduced liver bradykinin degradation and increased serum bradykinin levels. Finally, by blocking the breakdown of bradykinin, angiotensin-converting Enzyme inhibitors (ACEIs) increase serum bradykinin levels and induce brown adipose tissue thermogenesis and white adipose tissue browning via B2R. Collectively, our data provide new insights into the mechanisms underlying organ crosstalk in whole-body physiology control during cold exposure and also suggest bradykinin as a possible anti-obesity target.

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