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Publication : The Gq signalling pathway inhibits brown and beige adipose tissue.

First Author  Klepac K Year  2016
Journal  Nat Commun Volume  7
Pages  10895 PubMed ID  26955961
Mgi Jnum  J:236503 Mgi Id  MGI:5806214
Doi  10.1038/ncomms10895 Citation  Klepac K, et al. (2016) The Gq signalling pathway inhibits brown and beige adipose tissue. Nat Commun 7:10895
abstractText  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.
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