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Nat Commun. 2016 Mar 9;7:10895. doi: 10.1038/ncomms10895.

The Gq signalling pathway inhibits brown and beige adipose tissue.

Author information

1
Institute of Pharmacology and Toxicology, University Hospital Bonn, University of Bonn, 53127 Bonn, Germany.
2
Research Training Group 1873, University of Bonn, 53127 Bonn, Germany.
3
Department of Pharmacology, University of California, San Diego, California 92093, USA.
4
Institute of Pharmaceutical Biology, University of Bonn, D-53115 Bonn, Germany.
5
Department of Medical and Clinical Genetics, Institute of Biomedicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg SE-405 30, Sweden.
6
Molecular Signalling Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892, USA.
7
Institute of Pharmacology, University of Heidelberg, D-69120 Heidelberg, Germany.
8
Department of Medicine, University of Leipzig, 04103 Leipzig, Germany.
9
Department of Medicine, University of California, San Diego, California 92093, USA.
10
PharmaCenter, University of Bonn, 53127 Bonn, Germany.

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.

PMID:
26955961
PMCID:
PMC4786868
DOI:
10.1038/ncomms10895
[Indexed for MEDLINE]
Free PMC Article

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