ADRA1A-Gαq signalling potentiates adipocyte thermogenesis through CKB and TNAP

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperLetterpeer-review

  • Janane F Rahbani, McGill University
  • ,
  • Charlotte Scholtes, McGill University
  • ,
  • Damien M Lagarde, McGill University
  • ,
  • Mohammed F Hussain, McGill University
  • ,
  • Anna Roesler, McGill University
  • ,
  • Christien B Dykstra, McGill University
  • ,
  • Jakub Bunk, McGill University
  • ,
  • Bozena Samborska, McGill University
  • ,
  • Shannon L O'Brien, University of Birmingham
  • ,
  • Emma Tripp, University of Birmingham
  • ,
  • Alain Pacis, McGill University
  • ,
  • Anthony R Angueira, University of Pennsylvania
  • ,
  • Olivia S Johansen, University of Copenhagen
  • ,
  • Jessica Cinkornpumin, McGill University
  • ,
  • Ishtiaque Hossain, McGill University
  • ,
  • Matthew D Lynes, Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, ME, USA.
  • ,
  • Yang Zhang, Harvard University
  • ,
  • Andrew P White, Harvard University
  • ,
  • William A Pastor, McGill University
  • ,
  • Maria Chondronikola, University of California at San Diego, Harokopio University
  • ,
  • Labros Sidossis, Rutgers - The State University of New Jersey, New Brunswick
  • ,
  • Samuel Klein, George Washington University
  • ,
  • Anastasia Kralli, Johns Hopkins University
  • ,
  • Aaron M Cypess, National Institute of Environmental Health Sciences, National Institutes of Health
  • ,
  • Steen B Pedersen
  • Niels Jessen
  • Yu-Hua Tseng, Harvard University
  • ,
  • Zachary Gerhart-Hines, University of Copenhagen
  • ,
  • Patrick Seale, University of Pennsylvania
  • ,
  • Davide Calebiro, University of Birmingham
  • ,
  • Vincent Giguère, McGill University
  • ,
  • Lawrence Kazak, McGill University

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
JournalNature Metabolism
Volume4
Issue11
Pages (from-to)1459-1473
Number of pages15
ISSN2522-5812
DOIs
Publication statusPublished - Nov 2022

Bibliographical note

© 2022. The Author(s).

    Research areas

  • Adipocytes/metabolism, Creatine Kinase/metabolism, Creatine/metabolism, Energy Metabolism/genetics, Thermogenesis/genetics

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