2. Academic Validation
  3. TRPC5 deletion in the central amygdala antagonizes high-fat diet-induced obesity by increasing sympathetic innervation

TRPC5 deletion in the central amygdala antagonizes high-fat diet-induced obesity by increasing sympathetic innervation

  • Int J Obes (Lond). 2022 Aug;46(8):1544-1555. doi: 10.1038/s41366-022-01151-x.
Huan Ma 1,  Chengkang He 1,  Li Li 1,  Peng Gao 1,  Zongshi Lu 1,  Yingru Hu 1,  Lijuan Wang 1,  Yu Zhao 1,  Tingbing Cao 1,  Yuanting Cui 1,  Hongting Zheng 2,  Gangyi Yang 3,  Zhencheng Yan 1,  Daoyan Liu 1,  Zhiming Zhu 4 5
Affiliations

Affiliations

  • 1 Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, Army Medical University, Chongqing Institute of Hypertension, Chongqing, 400042, China.
  • 2 Department of Endocrinology, Translational Research Key Laboratory for Diabetes, Xinqiao Hospital, Army Medical University, Chongqing, 400037, China.
  • 3 Department of Endocrinology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.
  • 4 Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, Army Medical University, Chongqing Institute of Hypertension, Chongqing, 400042, China. [email protected].
  • 5 Chongqing Institute for Brain and Intelligence, Guangyang Bay Laboratory, Chongqing, 400064, China. [email protected].
PMID: 35589963 DOI: 10.1038/s41366-022-01151-x
Abstract

Transient receptor potential channel 5 (TRPC5) is predominantly distributed in the brain, especially in the central amygdala (CeA), which is closely associated with pain and addiction. Although mounting evidence indicates that the CeA is related to energy homeostasis, the possible regulatory effect of TRPC5 in the CeA on metabolism remains unclear. Here, we reported that the expression of TRPC5 in the CeA of mice was increased under a high-fat diet (HFD). Specifically, the deleted TRPC5 protein in the CeA of mice using adeno-associated virus resisted HFD-induced weight gain, accompanied by increased food intake. Furthermore, the energy expenditure of CeA-specific TRPC5 deletion mice (TRPC5 KO) was elevated due to augmented white adipose tissue (WAT) browning and brown adipose tissue (BAT) activity. Mechanistically, deficiency of TRPC5 in the CeA boosted nonshivering thermogenesis under cold stimulation by stimulating sympathetic nerves, as the β3-adrenoceptor (Adrb3) antagonist SR59230A blocked the effect of TRPC5 KO on this process. In summary, TRPC5 deletion in the CeA alleviated the metabolic deterioration of mice fed a HFD, and these phenotypic improvements were correlated with the increased sympathetic distribution and activity of adipose tissue.

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