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


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Copyright 2011 Fernø¸ et al. Except where otherwise noted, this item's license is described as Copyright 2011 Fernø¸ et al.

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