title: The fat-induced satiety factor oleoylethanolamide suppresses feeding through central release of oxytocin.
abstract: Oleoylethanolamide (OEA) is a biologically active lipid amide that is released by small-intestinal enterocytes during the absorption of dietary fat and inhibits feeding by engaging the nuclear receptor, peroxisome proliferator-activated receptor-alpha (PPAR-alpha). Previous studies have shown that the anorexic effects of systemically administered OEA require the activation of sensory afferents of the vagus nerve. The central circuits involved in mediating OEA-induced hypophagia remain unknown. In the present study, we report the results of in situ hybridization and immunohistochemistry experiments in rats and mice, which show that systemic injections of OEA (5-10 mg kg(-1), intraperitoneal) enhance expression of the neuropeptide oxytocin in magnocellular neurons of the paraventricular nucleus (PVN) and supraoptic nucleus (SON) of the hypothalamus. No such effect is observed with other hypothalamic neuropeptides, including vasopressin, thyrotropin-releasing hormone and pro-opiomelanocortin. The increase in oxytocin expression elicited by OEA was absent in mutant PPAR-alpha-null mice. Pharmacological blockade of oxytocin receptors in the brain by intracerebroventricular infusion of the selective oxytocin antagonist, L-368,899, prevented the anorexic effects of OEA. The results suggest that OEA suppresses feeding by activating central oxytocin transmission.
authors.affiliation: Department of Physiology and Pharmacology V. Erspamer, Sapienza University of Rome, 00185 Rome, Italy. piomelli@uci.edu
authors.forename: Silvana
authors.initials: S
authors.lastname: Gaetani
authors.forename: Jin
authors.initials: J
authors.lastname: Fu
authors.forename: Tommaso
authors.initials: T
authors.lastname: Cassano
authors.forename: Pasqua
authors.initials: P
authors.lastname: Dipasquale
authors.forename: Adele
authors.initials: A
authors.lastname: Romano
authors.forename: Laura
authors.initials: L
authors.lastname: Righetti
authors.forename: Silvia
authors.initials: S
authors.lastname: Cianci
authors.forename: Leonardo
authors.initials: L
authors.lastname: Laconca
authors.forename: Elisa
authors.initials: E
authors.lastname: Giannini
authors.forename: Sergio
authors.initials: S
authors.lastname: Scaccianoce
authors.forename: Jérôme
authors.initials: J
authors.lastname: Mairesse
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cuomo
authors.forename: Daniele
authors.initials: D
authors.lastname: Piomelli
mesh_terms: D000818:Animals; D001892:Camphanes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D063388:Endocannabinoids; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009829:Oleic Acids / Q000494:pharmacology*; D010121:Oxytocin / Q000037:antagonists & inhibitors / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D047493:PPAR alpha / Q000172:deficiency; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects* / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013495:Supraoptic Nucleus / Q000187:drug effects* / Q000378:metabolism
chemical_list: D001892:Camphanes; D063388:Endocannabinoids; D009829:Oleic Acids; D047493:PPAR alpha; D010879:Piperazines; D012333:RNA, Messenger; C488250:oleoylethanolamide; D010121:Oxytocin; C086206:L 368899