title: Orexigenic effects of omentin-1 related to decreased CART and CRH gene expression and increased norepinephrine synthesis and release in the hypothalamus.
abstract: Omentin-1, a visceral fat depot-specific secretory protein, is inversely correlated with obesity and insulin resistance. We investigated, in rats, the effects of chronic omentin-1 administration (8 μg/kg, intraperitoneally, once daily for 14-days) on feeding behavior and related hypothalamic peptides and neurotransmitters. Food intake and body weight were recorded daily throughout the study. We found a significantly increased food intake compared to controls, but only in days 10-14, while body weight significantly increased since day 12 (P<0.05). Compared with vehicle, omentin-1 treatment led to a significant reduction in both cocaine and amphetamine-regulated transcript (CART) (P<0.05) and corticotrophin releasing hormone (CRH) (P<0.05) gene expression, while pro-opiomelanocortin (POMC), agouti-related peptide (AgRP), neuropeptide Y (NPY) and orexin-A gene expression were not modified with respect to vehicle-treated rats. We also found an increase in hypothalamic levodopa (l-dopa) (P<0.05) and norepinephrine (NE) (P<0.01) synthesis, without any effect on dopamine (DA) and serotonin (5-hydroxytryptamine, 5-HT) metabolism. Furthermore, in hypothalamic synaptosomes, omentin-1 (10-100 ng/ml) stimulated basal NE release (ANOVA, P<0.0001; post hoc, P<0.001 vs. vehicle), in a dose-dependent manner, leaving unaffected both basal and depolarization-induced DA and 5-HT release. Finally, when synaptosomes were co-perfused with leptin and omentin-1, we observed that leptin was able to reverse omentin-1-induced stimulation of NE. In conclusion, the orexigenic effects of omentin-1 could be related, at least in part, to decreased CART and CRH gene expression and increased NE synthesis and release in the hypothalamus.
authors.affiliation: Department of Pharmacy, "G. d'Annunzio" University, via dei Vestini 31, 66013 Chieti, Italy. brunetti@unich.it
authors.forename: Luigi
authors.initials: L
authors.lastname: Brunetti
authors.forename: Giustino
authors.initials: G
authors.lastname: Orlando
authors.forename: Claudio
authors.initials: C
authors.lastname: Ferrante
authors.forename: Lucia
authors.initials: L
authors.lastname: Recinella
authors.forename: Sheila
authors.initials: S
authors.lastname: Leone
authors.forename: Annalisa
authors.initials: A
authors.lastname: Chiavaroli
authors.forename: Chiara
authors.initials: C
authors.lastname: Di Nisio
authors.forename: Rugia
authors.initials: R
authors.lastname: Shohreh
authors.forename: Fabio
authors.initials: F
authors.lastname: Manippa
authors.forename: Adriana
authors.initials: A
authors.lastname: Ricciuti
authors.forename: Michele
authors.initials: M
authors.lastname: Vacca
mesh_terms: D000818:Animals; D019167:Appetite Stimulants / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000235:genetics* / Q000378:metabolism; D016207:Cytokines / Q000494:pharmacology / Q000502:physiology*; D002149:Energy Intake / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects; D058851:GPI-Linked Proteins / Q000494:pharmacology / Q000502:physiology; D015870:Gene Expression; D020868:Gene Silencing / Q000187:drug effects; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D037102:Lectins / Q000494:pharmacology / Q000502:physiology*; D020738:Leptin / Q000494:pharmacology / Q000502:physiology; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000096:biosynthesis / Q000378:metabolism; D009638:Norepinephrine / Q000096:biosynthesis* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013574:Synaptosomes / Q000378:metabolism; D015430:Weight Gain / Q000187:drug effects; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
chemical_list: D019167:Appetite Stimulants; D016207:Cytokines; D058851:GPI-Linked Proteins; C432397:ITLN1 protein, human; D037102:Lectins; D020738:Leptin; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; D003346:Corticotropin-Releasing Hormone; D009638:Norepinephrine