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    Maintaining energy homeostasis upon environmental challenges, such as cold or excess calorie intake, is essential to the fitness and survival of mammals. Drug discovery efforts targeting β-adrenergic signaling have not been fruitful after decades of intensive research. We recently identified a new beige fat regulatory pathway mediated via the nicotinic acetylcholine receptor subunit CHRNA2. Here, we generated fat-specific Chrna2 KO mice and observed thermogenic defects in cold and metabolic dysfunction upon dietary challenges caused by adipocyte-autonomous regulation in vivo. We found that CHRNA2 signaling is activated after acute high fat diet feeding and this effect is manifested through both UCP1- and creatine-mediated mechanisms. Furthermore, our data suggested that CHRNA2 signaling may activate glycolytic beige fat, a subpopulation of beige adipocytes mediated by GABPα emerging in the absence of β-adrenergic signaling. These findings reveal the biological significance of the CHRNA2 pathway in beige fat biogenesis and energy homeostasis. Copyright © 2020 Elsevier Inc. All rights reserved.


    Heejin Jun, Yingxu Ma, Yong Chen, Jianke Gong, Shanshan Liu, Jine Wang, Alexander J Knights, Xiaona Qiao, Margo P Emont, X Z Shawn Xu, Shingo Kajimura, Jun Wu. Adrenergic-Independent Signaling via CHRNA2 Regulates Beige Fat Activation. Developmental cell. 2020 Jul 06;54(1):106-116.e5

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    PMID: 32533922

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