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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.
Afiliación
  • Rahbani JF; Rosalind & Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada.
  • Scholtes C; Rosalind & Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada.
  • Lagarde DM; Rosalind & Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada.
  • Hussain MF; Rosalind & Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada.
  • Roesler A; Department of Biochemistry, McGill University, Montreal, Quebec, Canada.
  • Dykstra CB; Rosalind & Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada.
  • Bunk J; Department of Biochemistry, McGill University, Montreal, Quebec, Canada.
  • Samborska B; Rosalind & Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada.
  • O'Brien SL; Department of Biochemistry, McGill University, Montreal, Quebec, Canada.
  • Tripp E; Rosalind & Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada.
  • Pacis A; Department of Biochemistry, McGill University, Montreal, Quebec, Canada.
  • Angueira AR; Rosalind & Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada.
  • Johansen OS; Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK.
  • Cinkornpumin J; Centre of Membrane Proteins and Receptors (COMPARE), Universities of Birmingham and Nottingham, Birmingham, UK.
  • Hossain I; Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK.
  • Lynes MD; Centre of Membrane Proteins and Receptors (COMPARE), Universities of Birmingham and Nottingham, Birmingham, UK.
  • Zhang Y; Rosalind & Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada.
  • White AP; Institute for Diabetes, Obesity & Metabolism and Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Pastor WA; Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
  • Chondronikola M; Department of Biochemistry, McGill University, Montreal, Quebec, Canada.
  • Sidossis L; Department of Biochemistry, McGill University, Montreal, Quebec, Canada.
  • Klein S; Maine Medical Center Research Institute, Scarborough, ME, USA.
  • Kralli A; Section on Integrative Physiology and Metabolism, Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA.
  • Cypess AM; Department of Orthopaedic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
  • Pedersen SB; Rosalind & Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada.
  • Jessen N; Department of Biochemistry, McGill University, Montreal, Quebec, Canada.
  • Tseng YH; Department of Nutrition and Radiology, University of California, Davis, Davis, CA, USA.
  • Gerhart-Hines Z; Department of Nutrition and Dietetics, Harokopio University of Athens, Athens, Greece.
  • Seale P; Department of Kinesiology and Health, School of Arts and Sciences, Rutgers University, New Brunswick, NJ, USA.
  • Calebiro D; Division of Geriatrics and Nutritional Science, Washington University School of Medicine, St. Louis, MO, USA.
  • Giguère V; Department of Physiology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Kazak L; Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Nat Metab ; 4(11): 1459-1473, 2022 11.
Article en En | MEDLINE | ID: mdl-36344764
ABSTRACT
Noradrenaline (NA) regulates cold-stimulated adipocyte thermogenesis1. Aside from cAMP signalling downstream of ß-adrenergic receptor activation, how NA promotes thermogenic output is still not fully understood. Here, we show that coordinated α1-adrenergic receptor (AR) and ß3-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.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Creatina / Termogénesis Idioma: En Revista: Nat Metab Año: 2022 Tipo del documento: Article País de afiliación: Canadá
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Creatina / Termogénesis Idioma: En Revista: Nat Metab Año: 2022 Tipo del documento: Article País de afiliación: Canadá