The K+ channel TASK1 modulates β-adrenergic response in brown adipose tissue through the mineralocorticoid receptor pathway
The K+ channel TASK1 modulates β-adrenergic response in brown adipose tissue through the mineralocorticoid receptor pathway
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DOI：
10.1096/fj.15-277475
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发表时间：
2016-02-01
期刊：
影响因子：
4.8
通讯作者：
Amri, Ez-Zoubir
中科院分区：
文献类型：
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作者：
Pisani, Didier F.;Beranger, Guillaume E.;Amri, Ez-Zoubir
棕色脂肪组织（BAT）通过解偶联蛋白（UCP）-1的活性对适应性产热和消耗热量过剩是必不可少的。人类中的BAT对于治疗肥胖和相关疾病具有极大的意义。在这项研究中，Twik相关的酸敏感性K+通道（ASK）-1（pH-sensitive potassium channel，2-pore domain，subfamily K，member 3（Kcnk 3）gene）的表达与肥胖和冷暴露小鼠中Ucp 1的表达高度相关。此外，与对照组相比，Task 1-nullmice变得超重，主要是因为白色脂肪组织质量增加和BAT变白。与野生型小鼠来源的棕色脂肪细胞相比，Task 1（-/-）小鼠来源的棕色脂肪细胞显示出受损的β 3-肾上腺素能受体反应，其特征在于耗氧量、Ucp 1表达和脂解的减少。这种表型被认为是由盐皮质激素受体（MR）信号传导的加剧引起的，因为它被皮质激素模拟并被MR抑制剂逆转。我们的结论是，K+通道TASK 1通过调节β-肾上腺素能受体信号来控制棕色脂肪细胞的产热活性。
Brown adipose tissue (BAT) is essential for adaptive thermogenesis and dissipation of caloric excess through the activity of uncoupling protein (UCP)-1. BAT in humans is of great interest for the treatment of obesity and related diseases. In this study, the expression of Twik-related acid-sensitive K+ channel (TASK)-1 [a pH-sensitive potassium channel encoded by the potassium channel, 2-pore domain, subfamily K, member 3 (Kcnk3) gene] correlated highly with Ucp1 expression in obese and cold-exposed mice. In addition, Task1-nullmice, compared with their controls, became overweight, mainly because of an increase in white adipose tissue mass and BAT whitening. Task1(-/-) -mouse-derived brown adipocytes, compared with wild-typemouse-derived brown adipocytes, displayed an impaired beta 3-adrenergic receptor response that was characterized by a decrease in oxygen consumption, Ucp1 expression, and lipolysis. This phenotype was thought to be caused by an exacerbation of mineralocorticoid receptor (MR) signaling, given that it was mimicked by corticoids and reversed by an MR inhibitor. We concluded that the K+ channel TASK1 controls the thermogenic activity in brown adipocytes through modulation of beta-adrenergic receptor signaling.