title: Involvement of hypothalamic PI3K-STAT3 signalling in regulating appetite suppression mediated by amphetamine.
abstract: OBJECTIVE
  Appetite suppression induced by amphetamine has been attributed to its inhibition of neuropeptide Y (NPY) neurons and activation of pro-opiomelanocortin (POMC) neurons in the hypothalamus. This study examined whether STAT3 was involved in these actions of amphetamine.
  
  
  METHODS
  Rats were given amphetamine daily for 4 days. Changes in the expression of NPY, POMC, melanocortin MC3 receptors, PI3K and STAT3 in the hypothalamus were assessed by RT-PCR and Western blotting. Antisense oligonucleotides to STAT3 were also used.
  
  
  RESULTS
  Expression of NPY decreased with a maximum effect day 2 of amphetamine treatment. Expression of POMC, MC3 receptors, PI3K and STAT3 increased with a maximum response on day 2. Moreover, phosphorylation of STAT3 and its DNA binding activity increased and was expressed in a similar pattern. Infusion (i.c.v.) of STAT3 antisense at 60 min before amphetamine treatment, partly blocked amphetamine-induced anorexia and modulated expression of NPY, POMC, MC3 receptors and PI3K, indicating the involvement of STAT3 in amphetamine-treated rats.
  
  
  CONCLUSIONS
  Hypothalamic PI3K-STAT3 signalling participated in the regulation of NPY- and POMC-mediated appetite suppression. These findings may contribute to a better understanding of anorectic drugs.
authors.affiliation: Department of Food Science, Central Taiwan University of Science and Technology, Taichung City, Taiwan.
authors.forename: Shu-Chen
authors.initials: SC
authors.lastname: Chu
authors.forename: Pei-Ni
authors.initials: PN
authors.lastname: Chen
authors.forename: Yih-Shou
authors.initials: YS
authors.lastname: Hsieh
authors.forename: Ching-Han
authors.initials: CH
authors.lastname: Yu
authors.forename: Meng-Hsuan
authors.initials: MH
authors.lastname: Lin
authors.forename: Yan-Han
authors.initials: YH
authors.lastname: Lin
authors.forename: Dong-Yih
authors.initials: DY
authors.lastname: Kuo
mesh_terms: D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001066:Appetite / Q000187:drug effects; D001067:Appetite Depressants / Q000494:pharmacology; D001069:Appetite Regulation / Q000187:drug effects*; D015153:Blotting, Western; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000378:metabolism; D009478:Neuropeptide Y / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D001067:Appetite Depressants; D009478:Neuropeptide Y; D016376:Oligonucleotides, Antisense; D050796:STAT3 Transcription Factor; D011333:Pro-Opiomelanocortin; D000661:Amphetamine; D058539:Phosphatidylinositol 3-Kinase
keywords: NPY; PI3K; POMC; STAT3; appetite; brain