| First Author | Ikeda K | Year | 2017 |
| Journal | Nat Med | Volume | 23 |
| Issue | 12 | Pages | 1454-1465 |
| PubMed ID | 29131158 | Mgi Jnum | J:251812 |
| Mgi Id | MGI:6103452 | Doi | 10.1038/nm.4429 |
| Citation | Ikeda K, et al. (2017) UCP1-independent signaling involving SERCA2b-mediated calcium cycling regulates beige fat thermogenesis and systemic glucose homeostasis. Nat Med 23(12):1454-1465 |
| abstractText | 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 Ca(2+) cycling by sarco/endoplasmic reticulum Ca(2+)-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 Ca(2+) cycling by activation of alpha1- and/or beta3-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 Ca(2+) cycling. |
