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The roles of G-protein-coupled receptors (GPCRs) in the control of food intake and energy expenditure are being increasingly recognized, and new drug candidates targeting these receptors are making their entry into the clinic. GPCRs exert their action along the various sites of regulation of energy homeostasis control including the central nervous system, the pancreas, the gut and fat cells. Exciting new data about GPCRs recognizing and mediating the effects of lipid mediators and concerning receptors for which no endogenous ligands have been identified yet open new exciting avenues for the validation of additional drug targets. In addition, recently developed paradigms around the concepts of cross-talk regulation and functional selectivity should lead to the development of drugs with improved therapeutic efficacy and reduced undesirable effects. Some of these promising discoveries are discussed in the present article and accompanying papers.

Peripheral actions of GPCRs in energy homeostasis: view from the Chair