Modulation of Meal Pattern in the Rat by the Anorexic Lipid Mediator Oleoylethanolamide

Abstract

Oleoylethanolamide (OEA) is a structural analog of the endogenous cannabinoid anandamide, which does not activate cannabinoid receptors. The biosynthesis of OEA in rat small intestine is increased by feeding and reduced by fasting. Moreover, OEA decreases food intake in food-deprived rats via a mechanism that requires intact sensory fibers (Rodríguez de Fonseca, 2001). These results suggest that OEA may contribute to the peripheral regulation of feeding. In the present study, we have investigated the effects of systemic OEA administration (1-20 mg/kg, intraperitoneal) on meal pattern in free-feeding and food-deprived rats. In free-feeding animals, OEA delayed feeding onset in a dose-dependent manner, but had no effect on meal size or postmeal interval. In food-deprived animals, OEA both delayed feeding onset and reduced meal size. The selective effects of OEA in free-feeding rats are strikingly different from those of the serotonergic anorexiant d-fenfluramine (which delayed feeding and reduced meal size) and the intestinal peptide cholecystokinin (which reduced meal size). These results suggest that OEA may participate in the regulation of satiety and may provide a chemical scaffold for the design of novel appetite-suppressing medications.

Oleoylethanolamide-induced anorexia in rats is associated with locomotor impairment

“…2003; Gaetani et al. 2003), 5 and 10 mg/kg BW OEA reduced food intake of freely eating rats compared to vehicle, 1 and 4 h after IP infusion, whereas 1 mg/kg OEA reduced food intake only at 4 h after injection (Fig. 1A).…”

“…2003; Gaetani et al. 2003). Yet, the dose of 1 mg/kg OEA, which does not impair locomotion while reducing 4 h food intake and affecting satiety ratio and intermeal interval, could actually be the most appropriate dose to employ in future rat experiments addressing the physiological relevance of exogenous OEA.…”

“…2003; Gaetani et al. 2003; Azari et al. 2014), reliably reduces food intake, causes locomotor incapacitation, which is the likely cause of the observed OEA‐induced anorexia under the conditions tested.…”

Regulation of food intake by oleoylethanolamide

“…induce satiation). OEA selectively prolongs the latency of feeding onset [57]. 150 pmol-g -1 in the post-ingestive state [25].…”

“…In contrast, the peptide hormone cholecystokinin selectively reduces meal size [56]. OEA appears to operate through a distinct mechanism: when administered systemically to freefeeding rats or mice before dark, OEA increases feeding latency and decreases meal frequency, but has no effect on meal size [57] (table 2). Moreover, synthetic PPAR-a agonists have very similar effects [27].…”