title: Sympathetic activity controls fat-induced oleoylethanolamide signaling in small intestine.
abstract: Ingestion of dietary fat stimulates production of the small-intestinal satiety factors oleoylethanolamide (OEA) and N-palmitoyl-phosphatidylethanolamine (NPPE), which reduce food intake through a combination of local (OEA) and systemic (NPPE) actions. Previous studies have shown that sympathetic innervation of the gut is necessary for duodenal infusions of fat to induce satiety, suggesting that sympathetic activity may engage small-intestinal satiety signals such as OEA and NPPE. In the present study, we show that surgical resection of the sympathetic celiac-superior mesenteric ganglion complex, which sends projections to the upper gut, abolishes feeding-induced OEA production in rat small-intestinal cells. These effects are accounted for by suppression of OEA biosynthesis, and are mimicked by administration of the selective β2-adrenergic receptor antagonist ICI-118,551. We further show that sympathetic ganglionectomy or pharmacological blockade of β2-adrenergic receptors prevents NPPE release into the circulation. In addition, sympathetic ganglionectomy increases meal frequency and lowers satiety ratio, and these effects are corrected by pharmacological administration of OEA. The results suggest that sympathetic activity controls fat-induced satiety by enabling the coordinated production of local (OEA) and systemic (NPPE) satiety signals in the small intestine.
authors.affiliation: Department of Pharmacology, School of Medicine, University of California, Irvine, Irvine, California 92697-4625, USA.
authors.forename: Jin
authors.initials: J
authors.lastname: Fu
authors.forename: Nicholas V
authors.initials: NV
authors.lastname: Dipatrizio
authors.forename: Ana
authors.initials: A
authors.lastname: Guijarro
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Schwartz
authors.forename: Xiaosong
authors.initials: X
authors.lastname: Li
authors.forename: Silvana
authors.initials: S
authors.lastname: Gaetani
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Astarita
authors.forename: Daniele
authors.initials: D
authors.lastname: Piomelli
mesh_terms: D018674:Adrenergic Antagonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000581:Amidohydrolases / Q000378:metabolism; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004041:Dietary Fats / Q000494:pharmacology*; D004435:Eating / Q000187:drug effects / Q000502:physiology; D063388:Endocannabinoids; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology; D005502:Food; D005728:Ganglia, Sympathetic / Q000502:physiology; D015171:Ganglionectomy; D007421:Intestine, Small / Q000294:innervation* / Q000502:physiology*; D008297:Male; D009829:Oleic Acids / Q000378:metabolism / Q000502:physiology*; D010739:Phospholipase D / Q000378:metabolism; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects / Q000502:physiology; D012528:Satiety Response / Q000187:drug effects; D015398:Signal Transduction / Q000502:physiology*; D013562:Sympathectomy; D013564:Sympathetic Nervous System / Q000502:physiology*; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D018674:Adrenergic Antagonists; D000318:Adrenergic beta-Agonists; D000581:Amidohydrolases; D004041:Dietary Fats; D063388:Endocannabinoids; D009829:Oleic Acids; D010739:Phospholipase D; D011412:Propanolamines; D018343:Receptors, Adrenergic, beta-2; D000099252:Fatty Acid Amide Hydrolases; C488250:oleoylethanolamide; C026777:ICI 118551