Potential Metabolic and Behavioural Roles of the Putative Endo-cannabinoid Receptors GPR18, GPR55 and GPR119 in Feeding

摘要

Endocannabinoids are ancient biomolecules involved in several cellular (e.g., metabo-lism) and physiological (e.g., eating behaviour) functions. Indeed, eating behaviour alterations inmarijuana users have led to investigate the orexigenic/anorexigenic effects of cannabinoids in ani-mal/human models. This increasing body of research suggests that the endocannabinoid systemplays an important role in feeding control. Accordingly, within the endocannabinoid system, can-nabinoid receptors, enzymes and genes represent potential therapeutic targets for dealing with mul-tiple metabolic and behavioural dysfunctions (e.g., obesity, anorexia, etc.). Paradoxically, our un-derstanding on the endocannabinoid system as a cellular mediator is yet limited. For example: (i)only two cannabinoid receptors have been classified, but they are not enough to explain the phar-macological profile of several experimental effects induced by cannabinoids; and (ii) several orphanG protein-coupled receptors (GPCRs) interact with cannabinoids and we do not know how to clas-sify them (e.g., GPR18, GPR55 and GPR119; amongst others).On this basis, the present review attempts to summarize the lines of evidence supporting the poten-tial role of GPR18, GPR55 and GPR119 in metabolism and feeding control that may explain someof the divergent effects and puzzling data related to cannabinoid research. Moreover, their therapeu-tic potential in feeding behaviour alterations will be considered.