Inhibitory effect of the anorexic compound oleoylethanolamide on gastric emptying in control and overweight mice.
Gastric emptying regulates food intake. Oleoylethanolamide (OEA), an endogenous acylethanolamide chemically related to the endocannabinoid anandamide, inhibits food intake, but its effect on gastric emptying is unknown. Here, we investigated the effect and the role of OEA on gastric emptying in mice fed either a standard (STD) or a high-fat diet (HFD) for 14 weeks. Gastric emptying was reduced by OEA, but not by its saturated analog, palmitoylethanolamide. The effect of OEA was unaffected by rimonabant (cannabinoid CB1 receptor antagonist), SR144528 (cannabinoid CB2 receptor antagonist), 5'-iodoresiniferatoxin (transient receptor potential vanilloid type 1 antagonist), or MK886 (peroxisome proliferator-activated receptor-alpha) antagonist. Compared to STD mice, HFD mice showed delayed gastric emptying and higher levels of gastric OEA. HFD-induced increase in OEA levels was accompanied by increased expression of the OEA-synthesizing enzyme N-acyl-phosphatidylethanolamine-selective phospholipase D and decreased expression of the OEA-degrading enzyme fatty acid amide hydrolase. These results might suggest that elevation of gastric OEA could possibly contribute to the delayed gastric emptying observed in HFD-fed animals. HFD regulates OEA levels in the stomach through an increase of its biosynthesis and a decrease of its enzymatic degradation. The inhibitory effect of OEA on gastric emptying here observed might underlie part of the anorexic effects of this compound previously reported.
Aviello
Gabriella
G
Endocannabinoid Research Group, Department of Experimental Pharmacology, University of Naples Federico II, Naples, Italy.
Matias
Isabel
I
Capasso
Raffaele
R
Petrosino
Stefania
S
Borrelli
Francesca
F
Orlando
Pierangelo
P
Romano
Barbara
B
Capasso
Francesco
F
Di Marzo
Vincenzo
V
Izzo
Angelo A
AA
D000577:Amides; D000818:Animals; D001067:Appetite Depressants / Q000494:pharmacology*; D002186:Cannabinoids / Q000494:pharmacology; D004435:Eating / Q000187:drug effects; D063388:Endocannabinoids; D004983:Ethanolamines; D005746:Gastric Emptying / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009829:Oleic Acids / Q000494:pharmacology*; D010169:Palmitic Acids / Q000494:pharmacology
D000577:Amides; D001067:Appetite Depressants; D002186:Cannabinoids; D063388:Endocannabinoids; D004983:Ethanolamines; D009829:Oleic Acids; D010169:Palmitic Acids; C488250:oleoylethanolamide; C005958:palmidrol