Ghrelin: new molecular pathways modulating appetite and adiposity.

Ghrelin is a unique endogenous peptidic hormone regulating both hunger and adiposity. Many of the actions of ghrelin are modulated specifically by the central nervous system. A number of molecular events triggered via the activation of the ghrelin receptor (GHS-R1a), leading to increased levels of neuropeptide Y (NPY) and agoutirelated peptide (AgRP) and ultimately responsible for the orexigenic effect of ghrelin have been characterized. Moreover, the discovery of ghrelin O-acyltransferase (GOAT), the enzyme responsible for the octanoylation of ghrelin, provides a mechanism allowing specific targeting of the ghrelin/GHS-R1a system without affecting the role of des-acyl-ghrelin in other pathways involved in the regulation of energy balance. This review aims to summarize novel roles of ghrelin in energy balance, focusing particularly on both the newly identified neuronal pathways mediating the effects of ghrelin and on peripheral mechanisms leading to increased adiposity.