Olanzapine-induced hyperphagia and weight gain associate with orexigenic hypothalamic neuropeptide signaling without concomitant AMPK phosphorylation
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Title: | Olanzapine-induced hyperphagia and weight gain associate with orexigenic hypothalamic neuropeptide signaling without concomitant AMPK phosphorylation |
Author: | Fernø, Johan Varela Fernández, Luis Skrede, Silje Vázquez Villar, María Jesús Nogueiras Pozo, Rubén Diéguez González, Carlos Vidal Puig, Antonio Steen, Vidar M. López Pérez, Miguel Antonio |
Affiliation: | Universidade de Santiago de Compostela. Departamento de Fisioloxía |
Date of Issue: | 2011 |
Publisher: | PLOS |
Citation: | Fernø J, Varela L, Skrede S, Vázquez MJ, Nogueiras R, Diéguez C, et al. (2011) Olanzapine-Induced Hyperphagia and Weight Gain Associate with Orexigenic Hypothalamic Neuropeptide Signaling without Concomitant AMPK Phosphorylation. PLoS ONE 6(6): e20571. https://doi.org/10.1371/journal.pone.0020571 |
Abstract: | The success of antipsychotic drug treatment in patients with schizophrenia is limited by the propensity of these drugs to induce hyperphagia, weight gain and other metabolic disturbances, particularly evident for olanzapine and clozapine. However, the molecular mechanisms involved in antipsychotic-induced hyperphagia remain unclear. Here, we investigate the effect of olanzapine administration on the regulation of hypothalamic mechanisms controlling food intake, namely neuropeptide expression and AMP-activated protein kinase (AMPK) phosphorylation in rats. Our results show that subchronic exposure to olanzapine upregulates neuropeptide Y (NPY) and agouti related protein (AgRP) and downregulates proopiomelanocortin (POMC) in the arcuate nucleus of the hypothalamus (ARC). This effect was evident both in rats fed ad libitum and in pair-fed rats. Of note, despite weight gain and increased expression of orexigenic neuropeptides, subchronic administration of olanzapine decreased AMPK phosphorylation levels. This reduction in AMPK was not observed after acute administration of either olanzapine or clozapine. Overall, our data suggest that olanzapine-induced hyperphagia is mediated through appropriate changes in hypothalamic neuropeptides, and that this effect does not require concomitant AMPK activation. Our data shed new light on the hypothalamic mechanism underlying antipsychotic-induced hyperphagia and weight gain, and provide the basis for alternative targets to control energy balance. |
Publisher version: | https://doi.org/10.1371/journal.pone.0020571 |
URI: | http://hdl.handle.net/10347/22018 |
DOI: | 10.1371/journal.pone.0020571 |
E-ISSN: | 1932-6203 |
Rights: | © 2011 Fernø et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
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Except where otherwise noted, this item's license is described as © 2011 Fernø et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.