Oleoylethanolamide affects food intake and sleep-waking cycle through a hypothalamic modulation.

Oleoylethanolamide (OEA) is an endogenous molecule related to endocannabinoids (eCBs) that induces satiety. It binds to the peroxisome-proliferator-activated receptor alpha (PPAR alpha). PPAR alpha is involved in feeding regulation and it has been proposed to play a role in sleep modulation. The objective of the present work is to show if this molecule modifies the sleep-waking cycle through central mechanisms. We have found that the peripheral administration of OEA reduces food intake and increases waking with a concomitant reduction of rapid eye movement sleep. Additionally, this treatment produces deactivation of the lateral hypothalamus, as inferred from the c-Fos expression evaluation. Finally, intra-lateral hypothalamus injection of OEA has mirrored the effects induced by this molecule when it is peripherally administered. In conclusion, we show for the very first time that OEA can modify the sleep-waking cycle and food intake, apparently mediated by the lateral hypothalamus.