Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, Army Medical University, Chongqing Institute of Hypertension, Chongqing, 400042, China.
Department of Endocrinology, Translational Research Key Laboratory for Diabetes, Xinqiao Hospital, Army Medical University, Chongqing, 400037, China.
Int J Obes (Lond). 2022 Aug;46(8):1544-1555. doi: 10.1038/s41366-022-01151-x. Epub 2022 May 20.
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.
瞬时受体电位通道 5（TRPC5）主要分布于脑内，特别是在与疼痛和成瘾密切相关的中枢杏仁核（CeA）中。尽管越来越多的证据表明 CeA 与能量稳态有关，但 TRPC5 在 CeA 对代谢的可能调节作用尚不清楚。本研究报道，高脂饮食（HFD）可增加小鼠 CeA 中的 TRPC5 表达。具体而言，利用腺相关病毒在小鼠 CeA 中敲除 TRPC5 蛋白可抵抗 HFD 诱导的体重增加，同时伴随着食物摄入量的增加。此外，CeA 特异性 TRPC5 缺失小鼠（TRPC5 KO）的能量消耗增加，这归因于白色脂肪组织（WAT）褐变和棕色脂肪组织（BAT）活性增强。在机制上，CeA 中 TRPC5 的缺失通过刺激交感神经增强非颤抖性产热，从而在冷刺激下促进 β3-肾上腺素能受体（Adrb3）拮抗剂 SR59230A 阻断 TRPC5 KO 对这一过程的影响。总之，CeA 中 TRPC5 的缺失缓解了 HFD 喂养小鼠的代谢恶化，这些表型改善与脂肪组织交感神经分布和活性的增加有关。
