ADRA1A-Gα signalling potentiates adipocyte thermogenesis through CKB and TNAP
MaineHealth Institute for Research
Creatine, Alkaline Phosphatase, Thermogenesis, Energy Metabolism, Adipocytes, Receptors, Adrenergic, Norepinephrine, Creatine Kinase, Estrogens
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.
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