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Olanzapine-Induced Hyperphagia and Weight Gain Associate with Orexigenic Hypothalamic Neuropeptide Signaling without Concomitant AMPK Phosphorylation

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dc.contributor.author Fernø, Johan eng
dc.contributor.author Varela, Luis eng
dc.contributor.author Skrede, Silje eng
dc.contributor.author Vázquez, María Jesús eng
dc.contributor.author Nogueiras, Rubén eng
dc.contributor.author Diéguez, Carlos eng
dc.contributor.author Vidal-Puig, Antonio eng
dc.contributor.author Steen, Vidar Martin eng
dc.contributor.author López, Miguel eng
dc.date.accessioned 2012-02-27T13:22:44Z
dc.date.available 2012-02-27T13:22:44Z
dc.date.issued 2011-06-13 eng
dc.identifier.citation PLoS ONE 6(6): e20571 en
dc.identifier.issn 1932-6203 eng
dc.identifier.uri http://hdl.handle.net/1956/5645
dc.description.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. en
dc.language.iso eng eng
dc.publisher Public Library of Science eng
dc.rights Attribution CC BY eng
dc.rights.uri http://creativecommons.org/licenses/by/2.5/ eng
dc.title Olanzapine-Induced Hyperphagia and Weight Gain Associate with Orexigenic Hypothalamic Neuropeptide Signaling without Concomitant AMPK Phosphorylation eng
dc.type Peer reviewed eng
dc.type Journal article eng
dc.subject.nsi VDP::Medical disciplines: 700::Clinical medical disciplines: 750::Psychiatry, child psychiatry: 757 eng
dc.rights.holder Copyright 2011 Fernø¸ et al.
dc.type.version publishedVersion eng
bora.peerreviewed Peer reviewed eng
bibo.doi http://dx.doi.org/10.1371/journal.pone.0020571 eng
dc.identifier.doi http://dx.doi.org/10.1371/journal.pone.0020571


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