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.