TrpC5 Mediates Acute Leptin and Serotonin Effects via Pomc Neurons.
TrpC5 Mediates Acute Leptin and Serotonin Effects via Pomc Neurons.
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TrpC5 通过 Pomc 神经元介导急性瘦素和血清素效应
DOI：
10.1016/j.celrep.2016.12.072
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发表时间：
2017-01-17
期刊：
影响因子：
8.8
通讯作者：
Williams KW
中科院分区：
文献类型：
--
作者：
Gao Y;Yao T;Deng Z;Sohn JW;Sun J;Huang Y;Kong X;Yu KJ;Wang RT;Chen H;Guo H;Yan J;Cunningham KA;Chang Y;Liu T;Williams KW
急性瘦素和5-羟色胺2C受体诱导的摄食减少的分子机制尚不清楚。在这里，我们表明，神经元和pro-opiomelanocortin（Pomc）特异性损失的瞬时受体电位阳离子5（TrpC 5）亚基是足以减少能量消耗和增加食物摄入量，导致体重升高。Pomc神经元中Trpc 5亚基的缺乏也足以阻断瘦素和5-羟色胺2C受体（Ht 2Cr）激动剂的促凋亡作用。这些受体的急性致氧化作用的损失是伴随着钝的电生理反应，瘦素和Ht 2Cr激动剂在弓状Pomc神经元。我们还表明，Ht 2Cr激动剂氯卡色林诱导的葡萄糖和胰岛素耐受性的改善被阻断的TrpC 5缺陷Pomc神经元。总之，我们的研究结果将大脑中的TrpC 5亚基与瘦素和5-羟色胺2C受体依赖的神经元活动变化以及能量平衡，进食行为和葡萄糖代谢联系起来。TrpC 5亚基对于与Pomc神经元激活相关的负能量平衡是必不可少的。TrpC 5亚基不仅连接瘦素和5-羟色胺受体在Pomc神经元的急性活动，而且直接调节基础代谢，可能提供一个内源性靶点来调控参与能量平衡和葡萄糖代谢调节的关键神经元的活动。
The molecular mechanisms underlying acute leptin and serotonin 2C receptor induced hypophagia remain unclear. Here we show that neuronal and pro-opiomelanocortin (Pomc)-specific loss of transient receptor potential cation 5 (TrpC5) subunits is sufficient to decrease energy expenditure and increase food intake resulting in elevated body weight. Deficiency of Trpc5 subunits in Pomc neurons was also sufficient to block the anorexigenic effects of leptin and serotonin 2C receptor (Ht2Cr) agonists. The loss of acute anorexigenic effects of these receptors was concomitant with a blunted electrophysiological response to both leptin and Ht2Cr agonists in arcuate Pomc neurons. We also demonstrate that the Ht2Cr agonist lorcaserin-induced improvements in glucose and insulin tolerance were blocked by TrpC5 deficiency in Pomc neurons. Together, our results link TrpC5 subunits in the brain with leptin- and serotonin 2C receptor-dependent changes in neuronal activity as well as energy balance, feeding behavior, and glucose metabolism. TrpC5 subunits are essential for the negative energy balance associated with Pomc neuronal activation. TrpC5 subunits not only link the acute activities of leptin and serotonin receptors in Pomc neurons, but also modify direct effects on basal metabolism.TrpC5 subunits may provide an endogenous target to manipulate the activity of key neurons involved in the regulation of energy balance and glucose metabolism.