RT Journal Article
T1 Olanzapine-induced hyperphagia and weight gain associate with orexigenic hypothalamic neuropeptide signaling without concomitant AMPK phosphorylation
A1 Fernø, Johan
A1 Varela Fernández, Luis
A1 Skrede, Silje
A1 Vázquez Villar, María Jesús
A1 Nogueiras Pozo, Rubén
A1 Diéguez González, Carlos
A1 Vidal Puig, Antonio
A1 Steen, Vidar M.
A1 López Pérez, Miguel A.
AB 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.
PB PLOS
YR 2011
FD 2011
LK http://hdl.handle.net/10347/22018
UL http://hdl.handle.net/10347/22018
LA eng
NO 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
NO The present study has been supported by grants from the Research Council of Norway (incl. the FUGE program and “PSYKISK HELSE” program), Norwegian Council for Mental Health, Extrastiftelsen Helse og Rehabilitering (JF), Helse Vest RHF, Dr. Einar Martens Fund, European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreements n° 245009 and 223713 (CD, ML and RN) and n° 018734 (AVP), Xunta de Galicia (ML: 10PXIB208164PR; RN: 2010/14)), Fondo Investigationes Sanitarias (ML: PS09/01880), Ministerio de Educacion y Ciencia (CD: BFU2008-02001; ML: RyC-2007-00211; RN: RyC-2008-02219 and SAF2009-07049;), Medical Research Council (AVP) and Welcome Trust (AVP). CIBER de Fisiopatología de la Obesidad y Nutrición is an initiative of ISCIII
DS Minerva
RD 28 abr 2026