ADRA1A-Gα q signalling potentiates adipocyte thermogenesis through CKB and TNAP.

Autor: 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.; Department of Biochemistry, McGill University, Montreal, Quebec, Canada., Roesler A; Rosalind & Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada.; Department of Biochemistry, McGill University, Montreal, Quebec, Canada., Dykstra CB; Rosalind & Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada.; Department of Biochemistry, McGill University, Montreal, Quebec, Canada., Bunk J; Rosalind & Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada.; Department of Biochemistry, McGill University, Montreal, Quebec, Canada., Samborska B; Rosalind & Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada., O'Brien SL; Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK.; Centre of Membrane Proteins and Receptors (COMPARE), Universities of Birmingham and Nottingham, Birmingham, UK., Tripp E; Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK.; Centre of Membrane Proteins and Receptors (COMPARE), Universities of Birmingham and Nottingham, Birmingham, UK., Pacis A; Rosalind & Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada., Angueira AR; Institute for Diabetes, Obesity & Metabolism and Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Johansen OS; Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark., Cinkornpumin J; Department of Biochemistry, McGill University, Montreal, Quebec, Canada., Hossain I; Department of Biochemistry, McGill University, Montreal, Quebec, Canada., Lynes MD; Maine Medical Center Research Institute, Scarborough, ME, USA., Zhang Y; Section on Integrative Physiology and Metabolism, Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA., White AP; Department of Orthopaedic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA., Pastor WA; Rosalind & Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada.; Department of Biochemistry, McGill University, Montreal, Quebec, Canada., Chondronikola M; Department of Nutrition and Radiology, University of California, Davis, Davis, CA, USA.; Department of Nutrition and Dietetics, Harokopio University of Athens, Athens, Greece., Sidossis L; Department of Kinesiology and Health, School of Arts and Sciences, Rutgers University, New Brunswick, NJ, USA., Klein S; Division of Geriatrics and Nutritional Science, Washington University School of Medicine, St. Louis, MO, USA., Kralli A; Department of Physiology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA., Cypess AM; Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA., Pedersen SB; Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Aarhus N, Denmark., Jessen N; Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Aarhus N, Denmark.; Department of Biomedicine, Aarhus University, Aarhus C, Denmark., Tseng YH; Section on Integrative Physiology and Metabolism, Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA., Gerhart-Hines Z; Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark., Seale P; Institute for Diabetes, Obesity & Metabolism and Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Calebiro D; Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK.; Centre of Membrane Proteins and Receptors (COMPARE), Universities of Birmingham and Nottingham, Birmingham, UK., Giguère V; Rosalind & Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada.; Department of Biochemistry, McGill University, Montreal, Quebec, Canada., Kazak L; Rosalind & Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada. lawrence.kazak@mcgill.ca.; Department of Biochemistry, McGill University, Montreal, Quebec, Canada. lawrence.kazak@mcgill.ca.
Jazyk: angličtina
Zdroj: Nature metabolism [Nat Metab] 2022 Nov; Vol. 4 (11), pp. 1459-1473. Date of Electronic Publication: 2022 Nov 07.
DOI: 10.1038/s42255-022-00667-w
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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