ADRA1A–Gαq signalling potentiates adipocyte thermogenesis through CKB and TNAP
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ADRA1A–Gαq signalling potentiates adipocyte thermogenesis through CKB and TNAP. / Rahbani, Janane F.; Scholtes, Charlotte; Lagarde, Damien M.; Hussain, Mohammed F.; Roesler, Anna; Dykstra, Christien B.; Bunk, Jakub; Samborska, Bozena; O’Brien, Shannon L.; Tripp, Emma; Pacis, Alain; Angueira, Anthony R.; Johansen, Olivia S.; Cinkornpumin, Jessica; Hossain, Ishtiaque; Lynes, Matthew D.; Zhang, Yang; White, Andrew P.; Pastor, William A.; Chondronikola, Maria; Sidossis, Labros; Klein, Samuel; Kralli, Anastasia; Cypess, Aaron M.; Pedersen, Steen B.; Jessen, Niels; Tseng, Yu Hua; Gerhart-Hines, Zachary; Seale, Patrick; Calebiro, Davide; Giguère, Vincent; Kazak, Lawrence.
In: Nature Metabolism, Vol. 4, No. 11, 2022, p. 1459-1473.Research output: Contribution to journal › Letter › Research › peer-review
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TY - JOUR
T1 - ADRA1A–Gαq signalling potentiates adipocyte thermogenesis through CKB and TNAP
AU - Rahbani, Janane F.
AU - Scholtes, Charlotte
AU - Lagarde, Damien M.
AU - Hussain, Mohammed F.
AU - Roesler, Anna
AU - Dykstra, Christien B.
AU - Bunk, Jakub
AU - Samborska, Bozena
AU - O’Brien, Shannon L.
AU - Tripp, Emma
AU - Pacis, Alain
AU - Angueira, Anthony R.
AU - Johansen, Olivia S.
AU - Cinkornpumin, Jessica
AU - Hossain, Ishtiaque
AU - Lynes, Matthew D.
AU - Zhang, Yang
AU - White, Andrew P.
AU - Pastor, William A.
AU - Chondronikola, Maria
AU - Sidossis, Labros
AU - Klein, Samuel
AU - Kralli, Anastasia
AU - Cypess, Aaron M.
AU - Pedersen, Steen B.
AU - Jessen, Niels
AU - Tseng, Yu Hua
AU - Gerhart-Hines, Zachary
AU - Seale, Patrick
AU - Calebiro, Davide
AU - Giguère, Vincent
AU - Kazak, Lawrence
N1 - Publisher Copyright: © 2022, The Author(s).
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
U2 - 10.1038/s42255-022-00667-w
DO - 10.1038/s42255-022-00667-w
M3 - Letter
C2 - 36344764
AN - SCOPUS:85141348645
VL - 4
SP - 1459
EP - 1473
JO - Nature Metabolism
JF - Nature Metabolism
SN - 2522-5812
IS - 11
ER -
ID: 327321076