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ADRA1A–Gα(q) signalling potentiates adipocyte thermogenesis through CKB and TNAP

Noradrenaline (NA) regulates cold-stimulated adipocyte thermogenesis(1). 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(1)-adrenergic receptor (AR) and β(3)-AR signalling in...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9684074/
https://www.ncbi.nlm.nih.gov/pubmed/36344764
http://dx.doi.org/10.1038/s42255-022-00667-w
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author 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
author_facet 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
author_sort Rahbani, Janane F.
collection PubMed
description Noradrenaline (NA) regulates cold-stimulated adipocyte thermogenesis(1). 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(1)-adrenergic receptor (AR) and β(3)-AR signalling induces the expression of thermogenic genes of the futile creatine cycle(2,3), 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 α(1)-AR subtype (ADRA1A) and Gα(q) 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(q) and Gα(s) 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(q)–futile creatine cycle axis is a key regulator of facultative and adaptive thermogenesis.
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spelling pubmed-96840742022-11-25 ADRA1A–Gα(q) 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 Nat Metab Letter Noradrenaline (NA) regulates cold-stimulated adipocyte thermogenesis(1). 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(1)-adrenergic receptor (AR) and β(3)-AR signalling induces the expression of thermogenic genes of the futile creatine cycle(2,3), 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 α(1)-AR subtype (ADRA1A) and Gα(q) 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(q) and Gα(s) 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(q)–futile creatine cycle axis is a key regulator of facultative and adaptive thermogenesis. Nature Publishing Group UK 2022-11-07 2022 /pmc/articles/PMC9684074/ /pubmed/36344764 http://dx.doi.org/10.1038/s42255-022-00667-w Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Letter
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
ADRA1A–Gα(q) signalling potentiates adipocyte thermogenesis through CKB and TNAP
title ADRA1A–Gα(q) signalling potentiates adipocyte thermogenesis through CKB and TNAP
title_full ADRA1A–Gα(q) signalling potentiates adipocyte thermogenesis through CKB and TNAP
title_fullStr ADRA1A–Gα(q) signalling potentiates adipocyte thermogenesis through CKB and TNAP
title_full_unstemmed ADRA1A–Gα(q) signalling potentiates adipocyte thermogenesis through CKB and TNAP
title_short ADRA1A–Gα(q) signalling potentiates adipocyte thermogenesis through CKB and TNAP
title_sort adra1a–gα(q) signalling potentiates adipocyte thermogenesis through ckb and tnap
topic Letter
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9684074/
https://www.ncbi.nlm.nih.gov/pubmed/36344764
http://dx.doi.org/10.1038/s42255-022-00667-w
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