产热
兰尼定受体
产热素
内分泌学
内科学
内质网
生物
兰尼碱受体2
能量稳态
糖酵解
己糖激酶
细胞生物学
化学
生物化学
脂肪组织
受体
新陈代谢
医学
作者
Kenji Ikeda,Qianqian Kang,Takeshi Yoneshiro,Joao Paulo Camporez,Hiroko Maki,Mayu Homma,Kosaku Shinoda,Yong Chen,Xiaodan Lu,Pema Maretich,Kazuki Tajima,Kolapo M. Ajuwon,Tomoyoshi Soga,Shingo Kajimura
出处
期刊:Nature Medicine
[Springer Nature]
日期:2017-11-13
卷期号:23 (12): 1454-1465
被引量:381
摘要
Uncoupling protein 1 (UCP1) plays a central role in nonshivering thermogenesis in brown fat; however, its role in beige fat remains unclear. Here we report a robust UCP1-independent thermogenic mechanism in beige fat that involves enhanced ATP-dependent Ca2+ cycling by sarco/endoplasmic reticulum Ca2+-ATPase 2b (SERCA2b) and ryanodine receptor 2 (RyR2). Inhibition of SERCA2b impairs UCP1-independent beige fat thermogenesis in humans and mice as well as in pigs, a species that lacks a functional UCP1 protein. Conversely, enhanced Ca2+ cycling by activation of α1- and/or β3-adrenergic receptors or the SERCA2b-RyR2 pathway stimulates UCP1-independent thermogenesis in beige adipocytes. In the absence of UCP1, beige fat dynamically expends glucose through enhanced glycolysis, tricarboxylic acid metabolism and pyruvate dehydrogenase activity for ATP-dependent thermogenesis through the SERCA2b pathway; beige fat thereby functions as a 'glucose sink' and improves glucose tolerance independently of body weight loss. Our study uncovers a noncanonical thermogenic mechanism through which beige fat controls whole-body energy homeostasis via Ca2+ cycling.
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