title: The Gq signalling pathway inhibits brown and beige adipose tissue.
abstract: Brown adipose tissue (BAT) dissipates nutritional energy as heat via the uncoupling protein-1 (UCP1) and BAT activity correlates with leanness in human adults. Here we profile G protein-coupled receptors (GPCRs) in brown adipocytes to identify druggable regulators of BAT. Twenty-one per cent of the GPCRs link to the Gq family, and inhibition of Gq signalling enhances differentiation of human and murine brown adipocytes. In contrast, activation of Gq signalling abrogates brown adipogenesis. We further identify the endothelin/Ednra pathway as an autocrine activator of Gq signalling in brown adipocytes. Expression of a constitutively active Gq protein in mice reduces UCP1 expression in BAT, whole-body energy expenditure and the number of brown-like/beige cells in white adipose tissue (WAT). Furthermore, expression of Gq in human WAT inversely correlates with UCP1 expression. Thus, our data indicate that Gq signalling regulates brown/beige adipocytes and inhibition of Gq signalling may be a novel therapeutic approach to combat obesity.
authors.affiliation: Institute of Pharmacology and Toxicology, University Hospital Bonn, University of Bonn, 53127 Bonn, Germany.|Research Training Group 1873, University of Bonn, 53127 Bonn, Germany.
authors.forename: Katarina
authors.initials: K
authors.lastname: Klepac
authors.affiliation: Institute of Pharmacology and Toxicology, University Hospital Bonn, University of Bonn, 53127 Bonn, Germany.|Research Training Group 1873, University of Bonn, 53127 Bonn, Germany.
authors.forename: Ana
authors.initials: A
authors.lastname: Kilić
authors.affiliation: Institute of Pharmacology and Toxicology, University Hospital Bonn, University of Bonn, 53127 Bonn, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Gnad
authors.affiliation: Institute of Pharmacology and Toxicology, University Hospital Bonn, University of Bonn, 53127 Bonn, Germany.|Department of Pharmacology, University of California, San Diego, California 92093, USA.
authors.forename: Loren M
authors.initials: LM
authors.lastname: Brown
authors.affiliation: Institute of Pharmacology and Toxicology, University Hospital Bonn, University of Bonn, 53127 Bonn, Germany.|Research Training Group 1873, University of Bonn, 53127 Bonn, Germany.
authors.forename: Beate
authors.initials: B
authors.lastname: Herrmann
authors.affiliation: Department of Pharmacology, University of California, San Diego, California 92093, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Wilderman
authors.affiliation: Institute of Pharmacology and Toxicology, University Hospital Bonn, University of Bonn, 53127 Bonn, Germany.
authors.forename: Aileen
authors.initials: A
authors.lastname: Balkow
authors.affiliation: Institute of Pharmacology and Toxicology, University Hospital Bonn, University of Bonn, 53127 Bonn, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Glöde
authors.affiliation: Research Training Group 1873, University of Bonn, 53127 Bonn, Germany.|Institute of Pharmaceutical Biology, University of Bonn, D-53115 Bonn, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Simon
authors.affiliation: Department of Medical and Clinical Genetics, Institute of Biomedicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg SE-405 30, Sweden.
authors.forename: Martin E
authors.initials: ME
authors.lastname: Lidell
authors.affiliation: Department of Medical and Clinical Genetics, Institute of Biomedicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg SE-405 30, Sweden.
authors.forename: Matthias J
authors.initials: MJ
authors.lastname: Betz
authors.affiliation: Department of Medical and Clinical Genetics, Institute of Biomedicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg SE-405 30, Sweden.
authors.forename: Sven
authors.initials: S
authors.lastname: Enerbäck
authors.affiliation: Molecular Signalling Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892, USA.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Wess
authors.affiliation: Institute of Pharmacology, University of Heidelberg, D-69120 Heidelberg, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Freichel
authors.affiliation: Department of Medicine, University of Leipzig, 04103 Leipzig, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Blüher
authors.affiliation: Institute of Pharmaceutical Biology, University of Bonn, D-53115 Bonn, Germany.
authors.forename: Gabi
authors.initials: G
authors.lastname: König
authors.affiliation: Research Training Group 1873, University of Bonn, 53127 Bonn, Germany.|Institute of Pharmaceutical Biology, University of Bonn, D-53115 Bonn, Germany.
authors.forename: Evi
authors.initials: E
authors.lastname: Kostenis
authors.affiliation: Department of Pharmacology, University of California, San Diego, California 92093, USA.|Department of Medicine, University of California, San Diego, California 92093, USA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Insel
authors.affiliation: Institute of Pharmacology and Toxicology, University Hospital Bonn, University of Bonn, 53127 Bonn, Germany.|Research Training Group 1873, University of Bonn, 53127 Bonn, Germany.|PharmaCenter, University of Bonn, 53127 Bonn, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Pfeifer
mesh_terms: D052437:Adipocytes, Brown / Q000166:cytology / Q000201:enzymology; D052438:Adipocytes, White / Q000166:cytology / Q000201:enzymology; D050156:Adipogenesis; D002001:Adipose Tissue, Brown / Q000201:enzymology*; D052436:Adipose Tissue, White / Q000201:enzymology*; D000818:Animals; D002454:Cell Differentiation; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D051379:Mice; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000071256:Uncoupling Protein 1
chemical_list: D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604371:UCP1 protein, human; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; D043802:GTP-Binding Protein alpha Subunits, Gq-G11