title: Participation of ghrelin signalling in the reciprocal regulation of hypothalamic NPY/POMC-mediated appetite control in amphetamine-treated rats.
abstract: Hypothalamic neuropeptide Y (NPY) and proopiomelanocortin (POMC) have been documented to participate in amphetamine (AMPH)-induced appetite suppression. This study investigated whether ghrelin signalling is associated with changes in NPY/POMC-mediated appetite control. Rats were given AMPH daily for four days, and changes in food intake, body weight, plasma ghrelin, hypothalamic NPY, melanocortin 3 receptor (MC3R), ghrelin O-acyltransferase (GOAT), acyl ghrelin (AG) and ghrelin receptor (GHSR1a) were examined and compared. Food intake, body weight and NPY expression decreased, while MC3R expression increased and expressed reciprocally to NPY expression during AMPH treatment. Plasma ghrelin and hypothalamic AG/GOAT/GHSR1a expression decreased on Day 1 and Day 2, which was associated with the positive energy metabolism, and returned to normal levels on Day 3 and Day 4, which was associated with the negative energy metabolism; this expression pattern was similar to that of NPY. Infusion with a GHSR1a antagonist or an NPY antisense into the brain enhanced the decrease in NPY and AG/GOAT/GHSR1a expression and the increase in MC3R expression compared to the AMPH-treated group. Peripheral ghrelin and the central ghrelin system participated in the regulation in AMPH-induced appetite control. These results shed light on the involvement of ghrelin signalling in reciprocal regulation of NPY/POMC-mediated appetite control and may prove useful for the development of anti-obesity drugs.
authors.affiliation: Department of Physiology, Chung Shan Medical University and Chung Shan Medical University Hospital, Taichung City 40201, Taiwan.
authors.forename: Ching-Han
authors.initials: CH
authors.lastname: Yu
authors.affiliation: Department of Food Science, Central Taiwan University of Science and Technology, Taichung City 406, Taiwan.
authors.forename: Shu-Chen
authors.initials: SC
authors.lastname: Chu
authors.affiliation: Institute of Biochemistry and Biotechnology, Chung Shan Medical University and Chung Shan Medical University Hospital, Taichung City 40201, Taiwan.
authors.forename: Pei-Ni
authors.initials: PN
authors.lastname: Chen
authors.affiliation: Institute of Biochemistry and Biotechnology, Chung Shan Medical University and Chung Shan Medical University Hospital, Taichung City 40201, Taiwan.
authors.forename: Yih-Shou
authors.initials: YS
authors.lastname: Hsieh
authors.affiliation: Department of Physiology, Chung Shan Medical University and Chung Shan Medical University Hospital, Taichung City 40201, Taiwan. Electronic address: dykuo@csmu.edu.tw.
authors.forename: Dong-Yih
authors.initials: DY
authors.lastname: Kuo
mesh_terms: D000217:Acyltransferases / Q000378:metabolism; D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001069:Appetite Regulation / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D004435:Eating / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D054439:Ghrelin / Q000097:blood*; D007031:Hypothalamus / Q000378:metabolism*; D008297:Male; D009478:Neuropeptide Y / Q000378:metabolism*; D011333:Pro-Opiomelanocortin / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D044104:Receptor, Melanocortin, Type 3 / Q000378:metabolism; D054440:Receptors, Ghrelin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000697:Central Nervous System Stimulants; D054439:Ghrelin; C571124:Ghsr1a protein, rat; D009478:Neuropeptide Y; D044104:Receptor, Melanocortin, Type 3; D054440:Receptors, Ghrelin; C514973:melanocortin 3 receptor, rat; D011333:Pro-Opiomelanocortin; D000661:Amphetamine; D000217:Acyltransferases; C534462:ghrelin O-acyltransferase, rat
keywords: Amphetamine; Appetite; Ghrelin signalling; Hypothalamus; NPY; POMC