Potential metabolic and behavioural roles of the putative endocannabinoid receptors GPR18, GPR55 and GPR119 in feeding.

Abstract

Endocannabinoids are ancient biomolecules involved in several cellular (e.g., metabolism) and physiological (e.g., eating behaviour) functions. Indeed, eating behaviour alterations in marijuana users have led to investigate the orexigen-ic/anorexigenic effects of cannabinoids in animal/human models. This increasing body of research suggests that the endo-cannabinoid system plays an important role in feeding control. Accordingly, within the endocannabinoid system, canna-binoid receptors, enzymes and genes represent potential therapeutic targets for dealing with multiple metabolic and behav-ioural dysfunctions (e.g., obesity, anorexia, etc.). Paradoxically, our understanding on the endocannabinoid system as a cel-lular mediator is yet limited. For example: (i) only two cannabinoid receptors have been classified, but they are not enough to explain the pharmacological profile of several experimental effects induced by cannabinoids; and (ii) several orphan G pro-tein-coupled receptors (GPCRs) interact with cannabinoids and we do not know how to classify them (e.g., GPR18, GPR55 and GPR119; amongst others).On this basis, the present review attempts to summarize the lines of evidence supporting the potential role of GPR18, GPR55 and GPR119 in metabolism and feeding control that may explain some of the divergent effects and puzzling data re-lated to cannabinoid research. Moreover, their therapeutic potential in feeding behaviour alterations will be considered.