학술논문
ADRA1A–Gαq signalling potentiates adipocyte thermogenesis through CKB and TNAP
Document Type
article
Author
Rahbani, Janane F; Scholtes, Charlotte; Lagarde, Damien M; Hussain, Mohammed F; Roesler, Anna; Dykstra, Christien B; Bunk, Jakub; Samborska, Bozena; O’Brien, Shannon L; Tripp, Emma; Pacis, Alain; Angueira, Anthony R; Johansen, Olivia S; Cinkornpumin, Jessica; Hossain, Ishtiaque; Lynes, Matthew D; Zhang, Yang; White, Andrew P; Pastor, William A; Chondronikola, Maria; Sidossis, Labros; Klein, Samuel; Kralli, Anastasia; Cypess, Aaron M; Pedersen, Steen B; Jessen, Niels; Tseng, Yu-Hua; Gerhart-Hines, Zachary; Seale, Patrick; Calebiro, Davide; Giguère, Vincent; Kazak, Lawrence
Source
Nature Metabolism. 4(11)
Subject
Language
Abstract
Noradrenaline (NA) regulates cold-stimulated adipocyte thermogenesis1. Aside from cAMP signalling downstream of β-adrenergic receptor activation, how NA promotes thermogenic output is still not fully understood. Here, we show that coordinated α1-adrenergic receptor (AR) and β3-AR signalling induces the expression of thermogenic genes of the futile creatine cycle2,3, and that early B cell factors, oestrogen-related receptors and PGC1α are required for this response in vivo. NA triggers physical and functional coupling between the α1-AR subtype (ADRA1A) and Gαq to promote adipocyte thermogenesis in a manner that is dependent on the effector proteins of the futile creatine cycle, creatine kinase B and tissue-non-specific alkaline phosphatase. Combined Gαq and Gαs signalling selectively in adipocytes promotes a continual rise in whole-body energy expenditure, and creatine kinase B is required for this effect. Thus, the ADRA1A-Gαq-futile creatine cycle axis is a key regulator of facultative and adaptive thermogenesis.