Oleoylethanolamide (OEA) is a biologically active lipid amide that is released by small-intestinal enterocytes during the absorption of dietary fat and inhibits feeding by engaging the nuclear receptor, peroxisome proliferator-activated receptor-alpha (PPAR-a).Systemic administration of OEA promotes, via afferent vagal fibers, expression of the activity-dependent gene c-fos in the paraventricular (PVN) and supraoptic (SON) nuclei of the hypothalamus.Neurons in these nuclei express a variety of neuropeptides, including oxytocin and vasopressin, which are involved in the central coordination of metabolic signals originated in peripheral tissues.The central oxytocin receptor blockade by the selective antagonist abrogates the ability of systemic OEA to alter feeding behavior, suggesting that peripheral OEA signaling suppresses food intake by activating oxytocin transmission in the hypothalamus.