title: The role of ghrelin signalling in second-generation antipsychotic-induced weight gain.
abstract: Based on clinical and animal studies, this review suggests a tri-phasic effect of second-generation antipsychotics (SGAs) on circulating ghrelin levels: an initial increase exerted by the acute effect of SGAs; followed by a secondary decrease possibly due to the negative feedback from the SGA-induced body weight gain or hyperphagia; and a final re-increase to reach the new equilibrium. Moreover, the results can also vary depending on individual SGAs, other hormonal states, dietary choices, and other confounding factors including medical history, co-treatments, age, gender, and ghrelin measurement techniques. Interestingly, rats treated with olanzapine, an SGA with high weight gain liabilities, are associated with increased hypothalamic ghrelin receptor (GHS-R1a) levels. In addition, expressions of downstream ghrelin signalling parameters at the hypothalamus, including neuropeptide Y (NPY)/agouti-related peptide (AgRP) and proopiomelanocortin (POMC) are also altered under SGA treatments. Thus, understanding the role of ghrelin signalling in antipsychotic drug-induced weight gain should offer potential novel pharmacological targets for tackling the obesity side-effect of SGAs and its associated metabolic syndrome.
authors: Centre for Translational Neuroscience, School of Medicine, University of Wollongong, Wollongong, NSW 2522, Australia; Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, NSW 2522, Australia.
authors: Qingsheng
authors: Q
authors: Zhang
authors: Chao
authors: C
authors: Deng
authors: Xu-Feng
authors: XF
authors: Huang
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects*; D054439:Ghrelin / Q000097:blood / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D015398:Signal Transduction / Q000187:drug effects; D015430:Weight Gain / Q000187:drug effects* / Q000502:physiology
chemical_list: D014150:Antipsychotic Agents; D054439:Ghrelin
keywords: AMPK; Antipsychotic; Ghrelin; Hypothalamus; Neuropeptides; Obesity