Nutritional and metabolic signalling through GPCRs

Abstract

Deregulated metabolism is a well-known feature of several challenging diseases, including diabetes, obesity and cancer. Besides their important role as intracellular bioenergetic molecules, dietary nutrients and metabolic intermediates are released in the extracellular environment. As such, they may achieve unconventional roles as hormone-like molecules by activating cell surface G-protein-coupled receptors (GPCRs) that regulate several pathophysiological processes. In this review, we provide an insight into the role of lactate, succinate, fatty acids, amino acids as well as ketogenesis-derived and b-oxidation-derived intermediates as extracellular signalling molecules. Moreover, the mechanisms by which their cognate metabolite-sensing GPCRs integrate nutritional and metabolic signals with specific intracellular pathways will be described. A better comprehension of these aspects is of fundamental importance to identify GPCRs as novel druggable targets.

Elevated Circulating Lactate Levels and Widespread Expression of Its Cognate Receptor, Hydroxycarboxylic Acid Receptor 1 (HCAR1), in Ovarian Cancer

“…Currently, an increasing body of evidence associates lactate signalling with multiple roles in the early development and progression of cancer via effects on tumour growth, angiogenesis, metastasis and immunosuppression [19]. In addition, lactate is seen to influence cytokine production through G protein-coupled receptor (GPCR) signalling [20]. Therefore, lactate's biomarker and prognostic potential are currently under exploration [12].…”