产热
生物
内分泌学
内科学
脂肪组织
褐色脂肪组织
脂肪细胞
调节器
细胞生物学
信号转导
串扰
产热素
生物化学
物理
光学
基因
医学
作者
Yi Chen,Xing Zeng,Xuan Huang,Sara Serag,Clifford J. Woolf,Bruce M. Spiegelman
出处
期刊:Cell
[Elsevier]
日期:2017-11-01
卷期号:171 (4): 836-848.e13
被引量:65
标识
DOI:10.1016/j.cell.2017.09.015
摘要
Summary
Adrenergic stimulation promotes lipid mobilization and oxidation in brown and beige adipocytes, where the harnessed energy is dissipated as heat in a process known as adaptive thermogenesis. The signaling cascades and energy-dissipating pathways that facilitate thermogenesis have been extensively described, yet little is known about the counterbalancing negative regulatory mechanisms. Here, we identify a two-pore-domain potassium channel, KCNK3, as a built-in rheostat negatively regulating thermogenesis. Kcnk3 is transcriptionally wired into the thermogenic program by PRDM16, a master regulator of thermogenesis. KCNK3 antagonizes norepinephrine-induced membrane depolarization by promoting potassium efflux in brown adipocytes. This limits calcium influx through voltage-dependent calcium channels and dampens adrenergic signaling, thereby attenuating lipolysis and thermogenic respiration. Adipose-specific Kcnk3 knockout mice display increased energy expenditure and are resistant to hypothermia and obesity. These findings uncover a critical K+-Ca2+-adrenergic signaling axis that acts to dampen thermogenesis, maintain tissue homeostasis, and reveal an electrophysiological regulatory mechanism of adipocyte function.
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