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

Author

Listed:
  • Fei Xiao

    (MOE Frontiers Center for Brain Science, Fudan University)

  • Haizhou Jiang

    (University of Chinese Academy of Sciences, Chinese Academy of Sciences)

  • Zi Li

    (University of Chinese Academy of Sciences, Chinese Academy of Sciences)

  • Xiaoxue Jiang

    (MOE Frontiers Center for Brain Science, Fudan University)

  • Shanghai Chen

    (MOE Frontiers Center for Brain Science, Fudan University)

  • Yuguo Niu

    (MOE Frontiers Center for Brain Science, Fudan University)

  • Hanrui Yin

    (University of Chinese Academy of Sciences, Chinese Academy of Sciences)

  • Yousheng Shu

    (MOE Frontiers Center for Brain Science, Fudan University)

  • Bo Peng

    (MOE Frontiers Center for Brain Science, Fudan University)

  • Wei Lu

    (MOE Frontiers Center for Brain Science, Fudan University)

  • Xiaoying Li

    (MOE Frontiers Center for Brain Science, Fudan University)

  • Zhigang Li

    (University of Chinese Academy of Sciences, Chinese Academy of Sciences)

  • Shujue Lan

    (Chinese Academy of Sciences)

  • Xiaoyan Xu

    (Chinese Academy of Sciences)

  • Feifan Guo

    (MOE Frontiers Center for Brain Science, Fudan University)

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.

Suggested Citation

  • Fei Xiao & Haizhou Jiang & Zi Li & Xiaoxue Jiang & Shanghai Chen & Yuguo Niu & Hanrui Yin & Yousheng Shu & Bo Peng & Wei Lu & Xiaoying Li & Zhigang Li & Shujue Lan & Xiaoyan Xu & Feifan Guo, 2023. "Reduced hepatic bradykinin degradation accounts for cold-induced BAT thermogenesis and WAT browning in male mice," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38141-0
    DOI: 10.1038/s41467-023-38141-0
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    References listed on IDEAS

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    1. Mengle Shao & Bo Shan & Yang Liu & Yiping Deng & Cheng Yan & Ying Wu & Ting Mao & Yifu Qiu & Yubo Zhou & Shan Jiang & Weiping Jia & Jingya Li & Jia Li & Liangyou Rui & Liu Yang & Yong Liu, 2014. "Hepatic IRE1α regulates fasting-induced metabolic adaptive programs through the XBP1s–PPARα axis signalling," Nature Communications, Nature, vol. 5(1), pages 1-12, May.
    2. Marion Peyrou & Rubén Cereijo & Tania Quesada-López & Laura Campderrós & Aleix Gavaldà-Navarro & Laura Liñares-Pose & Elena Kaschina & Thomas Unger & Miguel López & Marta Giralt & Francesc Villarroya, 2020. "The kallikrein–kinin pathway as a mechanism for auto-control of brown adipose tissue activity," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
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    Cited by:

    1. Xiaoxue Jiang & Kan liu & Peixiang Luo & Zi Li & Fei Xiao & Haizhou Jiang & Shangming Wu & Min Tang & Feixiang Yuan & Xiaoying Li & Yousheng Shu & Bo Peng & Shanghai Chen & Shihong Ni & Feifan Guo, 2024. "Hypothalamic SLC7A14 accounts for aging-reduced lipolysis in white adipose tissue of male mice," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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