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The G(q) signalling pathway inhibits brown and beige adipose tissue

Journal article
Authors K. Klepac
A. Kilic
T. Gnad
L. M. Brown
B. Herrmann
A. Wilderman
A. Balkow
A. Glode
K. Simon
M. E. Lidell
Mattias J. Betz
Sven Enerbäck
J. Wess
M. Freichel
M. Bluher
G. Konig
E. Kostenis
P. A. Insel
A. Pfeifer
Published in Nature Communications
Volume 7
Pages Article number: 10895
ISSN 2041-1723
Publication year 2016
Published at Institute of Biomedicine, Department of Medical and Clinical Genetics
Pages Article number: 10895
Language en
Links dx.doi.org/10.1038/ncomms10895
Keywords coupled receptor expression, lipoprotein-lipase gene, adipocytes, fat, endothelin-1, obesity, differentiation, progenitors, activation, cells
Subject categories Clinical Medicine

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 G(q) family, and inhibition of G(q) signalling enhances differentiation of human and murine brown adipocytes. In contrast, activation of G(q) signalling abrogates brown adipogenesis. We further identify the endothelin/Ednra pathway as an autocrine activator of G(q) signalling in brown adipocytes. Expression of a constitutively active G(q) 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 G(q) in human WAT inversely correlates with UCP1 expression. Thus, our data indicate that G(q) signalling regulates brown/beige adipocytes and inhibition of G(q) signalling may be a novel therapeutic approach to combat obesity.

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