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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.
Pubmed ID: 28988768 RIS Download
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View all literature mentionsThis monoclonal targets Vinculin antibody produced in mouse
View all literature mentionsThis polyclonal targets UCP1
View all literature mentionsThis monoclonal targets Aconitase 2 antibody [6F12BD9]
View all literature mentionsThis polyclonal targets beta 3 Adrenergic Receptor antibody
View all literature mentionsThis monoclonal targets PKA gamma (catalytic subunit) antibody [EP2647Y]
View all literature mentionsThis polyclonal targets Gs alpha
View all literature mentionsThis polyclonal targets Phospho-HSL (Ser563)
View all literature mentionsThis polyclonal targets Phospho-HSL (Ser660)
View all literature mentionsThe SciCrunch Infrastructure was developed as a cooperative data platform to be used by diverse communities in making data more FAIR.
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