title: NF-κB knockdown can modulate amphetamine-mediated feeding response.
abstract: This study determined if transcription factor NF-κB is involved in the effect of amphetamine (AMPH)-mediated feeding response. Moreover, possible roles of hypothalamic neuropeptide Y (NPY) and proopiomelanocortin (POMC) were also investigated. AMPH was administered daily to rats for four days. Changes in NF-κB, NPY and POMC expression were assessed and compared. The NPY gene was down-regulated with maximal response on Day 2 during AMPH treatment, which was consistent with the response to feeding behavior. In contrast, NF-κB and POMC genes were up-regulated, and their expression was increased by about 200% and 450%, respectively, with maximal response on Day 2. Moreover, NF-κB DNA binding ability and expression were increased similar to that of POMC. To examine further if NF-κB was involved, intracerebroventricular infusion of NF-κB antisense oligonucleotide was performed 1 h before the daily AMPH dosing in freely moving rats. Results showed that NF-κB knockdown could modify AMPH anorexia as well as NPY and POMC expression. The present findings prove that cerebral NF-κB participates in AMPH-mediated appetite suppression, possibly by modulating NPY and POMC expression. These results may aid in therapeutic research on AMPH and AMPH-like anti-obesity drugs.
authors.affiliation: Department of Physiology, Chung Shan Medical University and Chung Shan Medical University Hospital, Taichung City 40201, Taiwan, ROC. dykuo@csmu.edu.tw
authors.forename: Dong-Yih
authors.initials: DY
authors.lastname: Kuo
authors.forename: Pei-Ni
authors.initials: PN
authors.lastname: Chen
authors.forename: Meng-Hsien
authors.initials: MH
authors.lastname: Kuo
authors.forename: Chin-Hsiu
authors.initials: CH
authors.lastname: Chen
authors.forename: Yih-Shou
authors.initials: YS
authors.lastname: Hsieh
authors.forename: Shu-Chen
authors.initials: SC
authors.lastname: Chu
mesh_terms: D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001066:Appetite / Q000187:drug effects / Q000502:physiology; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects* / Q000502:physiology; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism; D020319:Oligodeoxyribonucleotides, Antisense; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000697:Central Nervous System Stimulants; D016328:NF-kappa B; D009478:Neuropeptide Y; D020319:Oligodeoxyribonucleotides, Antisense; D011333:Pro-Opiomelanocortin; D000661:Amphetamine