Oleoylethanolamide: effects on hypothalamic transmitters and gut peptides regulating food intake

Recently, it has been described the role of fatty acid ethanolamides in the control of feeding behavior. Oleoylethanolamide (OEA) is a member of this family of lipid mediators regulating feeding. OEA acts suppressing feeding behavior through, at least partially, a peripheral mechanism. However, the interaction between this acylethanolamide and other orexigenic or anorexigenic mediators is mostly not well characterized. The aim of this study was to evaluate whether anorectic actions of OEA were mediated through the modulation of central and peripheral signals involved in the regulation of feeding. Experiments were performed in male Wistar rats under free-feeding and fasting conditions. We measured hypothalamic neuropeptides and monoamines by in situ hybridization and HPLC respectively as well as plasmatic levels of relevant endocrine signals. OEA administration induced changes in hypothalamic monoaminergic activity and in the anorexigenic neuropeptide CART expressed in the paraventricular nucleus (PVN) but lacked effect on neuropeptides expression in nucleus arcuatus. In addition, OEA induced peripheral changes in gut peptides, with marked effects on PYY and Ghrelin. These results further suggest that anorexigenic properties of OEA are mediated by peripheral signals and by central alterations in neuropeptides expressed by feeding-involved hypothalamic structures receiving input from peripheral sensory systems, such as the PVN.