Reduced hepatic bradykinin degradation accounts for cold-induced BAT thermogenesis and WAT browning in male mice
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...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-05-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-38141-0 |
| _version_ | 1797832047856713728 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Fei Xiao |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-09T14:01:29Z |
| format | Article |
| id | doaj.art-c5e163e232a84bf3853467f9a482c1a3 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-04-09T14:01:29Z |
| publishDate | 2023-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-c5e163e232a84bf3853467f9a482c1a32023-05-07T11:17:57ZengNature PortfolioNature Communications2041-17232023-05-0114111710.1038/s41467-023-38141-0Reduced hepatic bradykinin degradation accounts for cold-induced BAT thermogenesis and WAT browning in male miceFei Xiao0Haizhou Jiang1Zi Li2Xiaoxue Jiang3Shanghai Chen4Yuguo Niu5Hanrui Yin6Yousheng Shu7Bo Peng8Wei Lu9Xiaoying Li10Zhigang Li11Shujue Lan12Xiaoyan Xu13Feifan Guo14Zhongshan Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Fudan UniversityCAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of SciencesCAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of SciencesZhongshan Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Fudan UniversityZhongshan Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Fudan UniversityZhongshan Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Fudan UniversityCAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of SciencesZhongshan Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Fudan UniversityZhongshan Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Fudan UniversityZhongshan Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Fudan UniversityZhongshan Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Fudan UniversityCAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of SciencesCenter for Excellence in Molecular Cell Science, Chinese Academy of SciencesCore Facility Center, CAS Center for Excellence in Molecular Plant Sciences, Chinese Academy of SciencesZhongshan Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Fudan UniversityAbstract 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.https://doi.org/10.1038/s41467-023-38141-0 |
| spellingShingle | 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 Reduced hepatic bradykinin degradation accounts for cold-induced BAT thermogenesis and WAT browning in male mice Nature Communications |
| title | Reduced hepatic bradykinin degradation accounts for cold-induced BAT thermogenesis and WAT browning in male mice |
| title_full | Reduced hepatic bradykinin degradation accounts for cold-induced BAT thermogenesis and WAT browning in male mice |
| title_fullStr | Reduced hepatic bradykinin degradation accounts for cold-induced BAT thermogenesis and WAT browning in male mice |
| title_full_unstemmed | Reduced hepatic bradykinin degradation accounts for cold-induced BAT thermogenesis and WAT browning in male mice |
| title_short | Reduced hepatic bradykinin degradation accounts for cold-induced BAT thermogenesis and WAT browning in male mice |
| title_sort | reduced hepatic bradykinin degradation accounts for cold induced bat thermogenesis and wat browning in male mice |
| url | https://doi.org/10.1038/s41467-023-38141-0 |
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