Abstract
Oleylethanolamide (OEA) is a natural analogue of the endogenous cannabinoid anandamide. Like anandamide, OEA is produced in cells in a stimulus-dependent manner and is rapidly eliminated by enzymatic hydrolysis, suggesting a function in cellular signalling. However, OEA does not activate cannabinoid receptors and its biological functions are still unknown. Here we show that, 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 gain in body mass. This anorexic effect is behaviourally selective and is associated with the discrete activation of brain regions (the paraventricular hypothalamic nucleus and the nucleus of the solitary tract) involved in the control of satiety. OEA does not affect food intake when injected into the brain ventricles, and its anorexic actions are prevented when peripheral sensory fibres are removed by treatment with capsaicin. These results indicate that OEA is a lipid mediator involved in the peripheral regulation of feeding.
Highlights
Oleylethanolamide (OEA) is a natural analogue of the endogenous cannabinoid anandamide
OEA does not affect food intake when injected into the brain ventricles, and its anorexic actions are prevented when peripheral sensory ®bres are removed by treatment with capsaicin
Fatty acid ethanolamides (FAEs) are unusual components of animal and plant lipids3±5 that are synthesized in response to a variety of physiological and pathological stimuli, including activation of neurotransmitter receptors in rat brain neurons[1,6] and exposure to metabolic stressors in mouse epidermal cells[7]
Summary
Administration of OEA causes a potent and persistent decrease in food intake and gain in body mass This anorexic effect is behaviourally selective and is associated with the discrete activation of brain regions (the paraventricular hypothalamic nucleus and the nucleus of the solitary tract) involved in the control of satiety. That animal cells release FAEs in a stimulus-dependent manner suggests that these compounds may participate in cell-tocell communication Further support for this idea comes from the discovery that the polyunsaturated FAE anandamide (arachidonylethanolamide) serves as an endogenous ligand for cannabinoid receptors[13]. Under the same conditions anandamide and oleic acid had no effect, palmitylethanolamide was signi®cantly less potent than OEA and elaidylethanolamide was similar in potency to OEA (Fig. 1a) These results indicate that OEA reduces eating in a structurally selective manner, and suggest that the molecular requisites for this effect are distinct from those involved in the interaction of anandamide with recognized cannabinoid.
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