title: Inhibiting neuropeptide Y Y1 receptor modulates melanocortin receptor- and NF-κB-mediated feeding behavior in phenylpropanolamine-treated rats.
abstract: Neuropeptide Y (NPY) and nuclear factor-kappa B (NF-κB) are involved in regulating anorexia elicited by phenylpropanolamine (PPA), a sympathomimetic drug. This study explored whether NPY Y1 receptor (Y1R) is involved in this process, and a potential role for the proopiomelanocortin system was identified. Rats were given PPA once a day for 4days. Changes in the hypothalamic expression of the NPY, Y1R, NF-κB, and melanocortin receptor 4 (MC4R) levels were assessed and compared. The results indicated that food intake and NPY expression decreased, with the largest reductions observed on Day 2 (approximately 50% and 45%, respectively), whereas NF-κB, MC4R, and Y1R increased, achieving maximums on Day 2 (160%, 200%, and 280%, respectively). To determine the role of Y1R, rats were pretreated with Y1R antisense or a Y1R antagonist via intracerebroventricular injection 1h before the daily PPA dose. Y1R knockdown and inhibition reduced PPA anorexia and partially restored the normal expression of NPY, MC4R, and NF-κB. The data suggest that hypothalamic Y1R participates in the appetite-suppression from PPA by regulating MC4R and NF-κB. The results of this study increase our understanding of the molecular mechanisms in PPA-induced anorexia.
authors.affiliation: Institute of Biochemistry and Biotechnology, Chung Shan Medical University and Chung Shan Medical University Hospital, Taichung City 40201, Taiwan, ROC.
authors.forename: Yih-Shou
authors.initials: YS
authors.lastname: Hsieh
authors.forename: Pei-Ni
authors.initials: PN
authors.lastname: Chen
authors.forename: Ching-Han
authors.initials: CH
authors.lastname: Yu
authors.forename: Jiuan-Miaw
authors.initials: JM
authors.lastname: Liao
authors.forename: Dong-Yih
authors.initials: DY
authors.lastname: Kuo
mesh_terms: D000818:Animals; D016375:Antisense Elements (Genetics); D001067:Appetite Depressants / Q000494:pharmacology*; D015153:Blotting, Western; D001835:Body Weight / Q000502:physiology; D002404:Catheterization; D002552:Cerebral Ventricles / Q000502:physiology; D005247:Feeding Behavior / Q000187:drug effects*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007245:Inferior Colliculi; D007267:Injections; D008297:Male; D016328:NF-kappa B / Q000096:biosynthesis / Q000187:drug effects*; D010665:Phenylpropanolamine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D044105:Receptor, Melanocortin, Type 4 / Q000096:biosynthesis; D044101:Receptors, Melanocortin / Q000096:biosynthesis / Q000187:drug effects*; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics
chemical_list: D016375:Antisense Elements (Genetics); D001067:Appetite Depressants; D016328:NF-kappa B; D044105:Receptor, Melanocortin, Type 4; D044101:Receptors, Melanocortin; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; D010665:Phenylpropanolamine