ADRA1A–Gαq signalling potentiates adipocyte thermogenesis through CKB and TNAP

Janane F. Rahbani, Charlotte Scholtes, Damien M. Lagarde, Mohammed F. Hussain, Anna Roesler, Christien B. Dykstra, Jakub Bunk, Bozena Samborska, Shannon L. O’Brien, Emma Tripp, Alain Pacis, Anthony R. Angueira, Olivia S. Johansen, Jessica Cinkornpumin, Ishtiaque Hossain, Matthew D. Lynes, Yang Zhang, Andrew P. White, William A. Pastor, Maria ChondronikolaLabros Sidossis, Samuel Klein, Anastasia Kralli, Aaron M. Cypess, Steen B. Pedersen, Niels Jessen, Yu Hua Tseng, Zachary Gerhart-Hines, Patrick Seale, Davide Calebiro, Vincent Giguère, Lawrence Kazak

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1459-1473
Number of pages15
JournalNature Metabolism
Issue number11
StatePublished - Nov 2022

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Physiology (medical)
  • Cell Biology


Dive into the research topics of 'ADRA1A–Gαq signalling potentiates adipocyte thermogenesis through CKB and TNAP'. Together they form a unique fingerprint.

Cite this