ADRA1A-Gα signalling potentiates adipocyte thermogenesis through CKB and TNAP

Authors

• Janane F. Rahbani, Rosalind & Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada.
• Charlotte Scholtes, Rosalind & Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada.
• Damien M. Lagarde, Rosalind & Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada.
• Mohammed F. Hussain, Rosalind & Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada.
• Anna Roesler, Rosalind & Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada.
• Christien B. Dykstra, Rosalind & Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada.
• Jakub Bunk, Rosalind & Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada.
• Bozena Samborska, Rosalind & Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada.
• Shannon L. O'Brien, Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK.
• Emma Tripp, Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK.
• Alain Pacis, Rosalind & Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada.
• Anthony R. Angueira, Institute for Diabetes, Obesity & Metabolism and Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
• Olivia S. Johansen, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
• Jessica Cinkornpumin, Department of Biochemistry, McGill University, Montreal, Quebec, Canada.
• Ishtiaque Hossain, Department of Biochemistry, McGill University, Montreal, Quebec, Canada.
• Matthew D. Lynes, MaineHealth Institute for ResearchFollow
• Yang Zhang, Section on Integrative Physiology and Metabolism, Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA.
• Andrew P. White, Department of Orthopaedic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
• William A. Pastor, Rosalind & Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada.
• Maria Chondronikola, Department of Nutrition and Radiology, University of California, Davis, Davis, CA, USA.
• Labros Sidossis, Department of Kinesiology and Health, School of Arts and Sciences, Rutgers University, New Brunswick, NJ, USA.
• Samuel Klein, Division of Geriatrics and Nutritional Science, Washington University School of Medicine, St. Louis, MO, USA.
• Anastasia Kralli, Department of Physiology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Document Type

Article

Publication Date

11-7-2022

Institution/Department

MaineHealth Institute for Research

Journal Title

Nature metabolism

MeSH Headings

Creatine, Alkaline Phosphatase, Thermogenesis, Energy Metabolism, Adipocytes, Receptors, Adrenergic, Norepinephrine, Creatine Kinase, Estrogens

Abstract

Noradrenaline (NA) regulates cold-stimulated adipocyte thermogenesis. 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 α-adrenergic receptor (AR) and β-AR signalling induces the expression of thermogenic genes of the futile creatine cycle, 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 α-AR subtype (ADRA1A) and Gα 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 Gα and Gα 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-Gα-futile creatine cycle axis is a key regulator of facultative and adaptive thermogenesis.

Recommended Citation

Rahbani JF, Scholtes C, Lagarde DM, et al. ADRA1A-Gαq signalling potentiates adipocyte thermogenesis through CKB and TNAP [published online ahead of print, 2022 Nov 7]. Nat Metab. 2022;10.1038/s42255-022-00667-w. doi:10.1038/s42255-022-00667-w