31° Congresso Nazionale della Società Italiana di Farmacologia
Trieste, 26-29 giugno 2003
ROLE OF OLEYLETHANOLAMIDE IN THE REGULATION OF FEEDING
BEHAVIOR
Gaetani S.1#, Fu J.1, Oveisi F.1, Rodríguez de Fonseca F.*, Cuomo V.# and Piomelli D.1
1
Dept. of Pharmacology, University of California, Irvine CA-USA; *Fundación Hospital
Carlos Haya, 29010 Málaga, Spain; #Dip. di Farmacologia delle Sostanze Naturali e Fisiologia
Generale, Fac. di Farmacia, Università degli Studi di Roma “La Sapienza”
Anandamide (AEA) was identified in 1992 as the first endogenous ligand for cannabinoid
receptors. AEA is a member of a family of lipids called fatty acid ethanolamides (FAEs),
which share common biosynthetic pathways and mechanisms of enzymatic degradation but,
besides AEA, do not activate cannabinoid receptors. Research on FAEs mediated signaling has
been largely confined to the endocannabinoid AEA, however it is now becoming apparent that
the cannabinoid receptor-inactive FAEs are of physiological and pathological interest. In this
study, we show that a member of this family, oleoylethanolamide (OEA), is a lipid mediator
involved in the peripheral regulation of feeding. In rats, food deprivation markedly reduces
OEA biosynthesis in the small intestine. Administration of OEA causes a potent and persistent
decrease in food intake and in body weight gain. This anorexic effect is behaviorally selective
and is associated with discrete activation of brain regions, such as the paraventricular
hypothalamic nucleus, the nucleus of the solitary tract and the supraoptic nucleus. In addition,
the effect is peripherally mediated, since (i) it is eliminated when sensory fibers are removed
by treatment with capsaicin, and (ii) it is not induced by intracerebroventricular OEA
administration. To further elucidate the role of OEA in feeding behavior, we determined the
dose-dependent effects of intraperitoneal (i.p.) administration of OEA on food intake and meal
pattern, both in food-deprived and in ad libitum feeding rats. Cumulative food intake was dose
dependently inhibited by OEA. This compound suppressed feeding by increasing the first meal
latency, by decreasing food intake in the first hour after the administration, and by decreasing
the number of meals. In a separate group of animals, OEA levels were analyzed in plasma by
HPLC/MS at different times after its administration (5 mg/kg). At 15 and 30 min we observed
an increase of OEA, which rapidly decreased at 60 min after administration suggesting that
this molecule is rapidly metabolized. Together, these results indicate that the suppressive
effect of OEA on food intake is associated with high level of OEA in plasma, and that this
effect may be mediated by an induction of satiety. Experiments are currently in progress to
clarify the molecular target of OEA and its possible mechanism of action.
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