Hypothalamic ghrelin signalling mediates olanzapine-induced hyperphagia and weight gain in female rats.
Excessive weight gain is a major metabolic side effect of second-generation antipsychotics (SGAs) in the treatment of schizophrenia. Ghrelin is an orexigenic hormone secreted mainly from the stomach, which can induce weight gain and hyperphagia through regulating neuropeptides at the hypothalamus. Accumulating evidence implicates a relationship between ghrelin signalling and SGA-induced hyperphagia and weight gain. We report that olanzapine (a SGA with high weight gain liability) potently and time-dependently up-regulate ghrelin and ghrelin signalling, leading to hyperphagia and weight gain in female Sprague-Dawley rats, an action reversed by i.c.v. injection of a ghrelin receptor (GHS-R1a) antagonist. These findings indicate a crucial role of ghrelin signalling in hyperphagia induced by olanzapine, supporting the notion that GHS-R1a antagonist may be useful for pharmacological treatment of SGA-induced weight gain resulted from hyperphagia.
Centre for Translational Neuroscience, School of Medicine, University of Wollongong, Wollongong, NSW, Australia.
Qingsheng
Q
Zhang
Centre for Translational Neuroscience, School of Medicine, University of Wollongong, Wollongong, NSW, Australia.
Meng
M
He
Centre for Translational Neuroscience, School of Medicine, University of Wollongong, Wollongong, NSW, Australia.
Chao
C
Deng
Centre for Translational Neuroscience, School of Medicine, University of Wollongong, Wollongong, NSW, Australia.
Hongqin
H
Wang
Centre for Translational Neuroscience, School of Medicine, University of Wollongong, Wollongong, NSW, Australia.
Jiamei
J
Lian
Centre for Translational Neuroscience, School of Medicine, University of Wollongong, Wollongong, NSW, Australia.
Xu-Feng
XF
Huang
D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects*; D001569:Benzodiazepines / Q000009:adverse effects*; D002491:Central Nervous System Agents / Q000494:pharmacology; D004435:Eating / Q000187:drug effects / Q000502:physiology; D005260:Female; D054439:Ghrelin / Q000097:blood / Q000378:metabolism*; D006963:Hyperphagia / Q000139:chemically induced* / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D000077152:Olanzapine; D009842:Oligopeptides / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D054440:Receptors, Ghrelin / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D015430:Weight Gain / Q000187:drug effects* / Q000502:physiology
D014150:Antipsychotic Agents; D002491:Central Nervous System Agents; C520836:GHRP-6, Lys(3)-; D054439:Ghrelin; D009479:Neuropeptides; D009842:Oligopeptides; D012333:RNA, Messenger; D054440:Receptors, Ghrelin; D014157:Transcription Factors; D001569:Benzodiazepines; D000077152:Olanzapine