The Gq signalling pathway inhibits brown and beige adipose tissue

Katarina Klepac, Ana Kilić, Thorsten Gnad, Loren M. Brown, Beate Herrmann, Andrea Wilderman, Aileen Balkow, Anja Glöde, Katharina Simon, Martin E. Lidell, Matthias J. Betz, Sven Enerbäck, Jürgen Wess, Marc Freichel, Matthias Blüher, Gabi König, Evi Kostenis, Paul A. Insel and Alexander Pfeifer ()
Additional contact information
Katarina Klepac: Institute of Pharmacology and Toxicology, University Hospital Bonn, University of Bonn
Ana Kilić: Institute of Pharmacology and Toxicology, University Hospital Bonn, University of Bonn
Thorsten Gnad: Institute of Pharmacology and Toxicology, University Hospital Bonn, University of Bonn
Loren M. Brown: Institute of Pharmacology and Toxicology, University Hospital Bonn, University of Bonn
Beate Herrmann: Institute of Pharmacology and Toxicology, University Hospital Bonn, University of Bonn
Andrea Wilderman: University of California
Aileen Balkow: Institute of Pharmacology and Toxicology, University Hospital Bonn, University of Bonn
Anja Glöde: Institute of Pharmacology and Toxicology, University Hospital Bonn, University of Bonn
Katharina Simon: Research Training Group 1873, University of Bonn
Martin E. Lidell: Institute of Biomedicine, The Sahlgrenska Academy, University of Gothenburg
Matthias J. Betz: Institute of Biomedicine, The Sahlgrenska Academy, University of Gothenburg
Sven Enerbäck: Institute of Biomedicine, The Sahlgrenska Academy, University of Gothenburg
Jürgen Wess: Molecular Signalling Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases
Marc Freichel: Institute of Pharmacology, University of Heidelberg
Matthias Blüher: University of Leipzig
Gabi König: Institute of Pharmaceutical Biology, University of Bonn
Evi Kostenis: Research Training Group 1873, University of Bonn
Paul A. Insel: University of California
Alexander Pfeifer: Institute of Pharmacology and Toxicology, University Hospital Bonn, University of Bonn

Nature Communications, 2016, vol. 7, issue 1, 1-10

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms10895

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