ADRA1A–Gαq signalling potentiates adipocyte thermogenesis through CKB and TNAP

Author:

Rahbani Janane F.ORCID,Scholtes CharlotteORCID,Lagarde Damien M.,Hussain Mohammed F.,Roesler Anna,Dykstra Christien B.ORCID,Bunk Jakub,Samborska Bozena,O’Brien Shannon L.,Tripp EmmaORCID,Pacis Alain,Angueira Anthony R.,Johansen Olivia S.,Cinkornpumin Jessica,Hossain IshtiaqueORCID,Lynes Matthew D.ORCID,Zhang Yang,White Andrew P.,Pastor William A.ORCID,Chondronikola Maria,Sidossis Labros,Klein Samuel,Kralli Anastasia,Cypess Aaron M.ORCID,Pedersen Steen B.ORCID,Jessen NielsORCID,Tseng Yu-HuaORCID,Gerhart-Hines ZacharyORCID,Seale PatrickORCID,Calebiro DavideORCID,Giguère VincentORCID,Kazak LawrenceORCID

Abstract

AbstractNoradrenaline (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.

Funder

Gouvernement du Canada | Canadian Institutes of Health Research

Publisher

Springer Science and Business Media LLC

Subject

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

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