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Alterations of lipid metabolism and gene expression in rat adipocytes during chronic olanzapine treatment

Molecular Psychiatry volume 12, pages 562–571 (2007)Cite this article

Abstract

Although antipsychotics are established drugs in schizophrenia treatment, they are admittedly known to induce side effects favoring the onset of obesity and worsening its complications. Despite potential involvement of histamine receptor antagonism, or of other neurotransmitter systems, the mechanism by which antipsychotic drugs increase body weight is not elucidated. The aim of the present study was to investigate whether chronic antipsychotic treatments can directly alter the regulation of two main functions of white adipose tissue: lipolysis and glucose utilization. The influence of a classical antipsychotic (haloperidol) was compared to that of two atypical antipsychotics, one known to favor weight gain (olanzapine), the other not (ziprasidone). Cell size, lipolytic capacity and glucose transport activity were determined in white adipocytes of rats subjected to 5-week oral treatment with these antipsychotics. Gene expression of adipocyte proteins involved in glucose transport or fat storage and mobilization, such as glucose transporters (GLUT1 and GLUT4), leptin, matrix metallo-proteinase-9 (MMP9), hormone-sensitive lipase (HSL) and fatty acid synthase (FAS) was also evaluated. Adipocytes from chronic olanzapine-treated rats exhibited decreased lipolytic activity, lowered HSL expression and increased FAS expression. These changes were concomitant to enlarged fat deposition and adipocyte size. Alterations were observed in adipocytes from olanzapine-treated rats whereas the other antipsychotics did not induce any notable disorder. Our results therefore show evidence of an effect of chronic antipsychotic treatment on rat adipocyte metabolism. Thus, impairment of fat cell lipolysis should be considered as a side effect of certain antipsychotics, leading, along with the already documented hyperphagia, to the excessive weight gain observed in patients under prolonged treatment.

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Acknowledgements

This study was supported by a grant from Pfizer (New York). Julie Minet-Ringuet was supported by a grant from La Fondation pour la Recherche Médicale. We thank Brooke Maddux for re-reading and correcting the manuscript.

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Authors and Affiliations

  1. Laboratoire de Psychopharmacologie, Centre Hospitalier Paul Guiraud, Villejuif, France

    J Minet-Ringuet & R de Beaurepaire

  2. INRA, UMR physiologie de la nutrition et du comportement alimentaire, Institut National Agronomique Paris-Grignon, Paris Cedex, France

    J Minet-Ringuet, P C Even & D Tomé

  3. INSERM, U586, Unité de recherche sur les Obésités, Université Paul Sabatier, Institut Louis Bugnard IFR31, Toulouse, France

    P Valet, C Carpéné, V Visentin, D Prévot & D Daviaud

  4. INSERM, U465, Faculté de médecine, rue de l'école de médecine, Paris, France

    A Quignard-Boulange

  5. INSERM, U513, Créteil, France

    R de Beaurepaire

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  1. J Minet-Ringuet
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Correspondence to R de Beaurepaire.

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Minet-Ringuet, J., Even, P., Valet, P. et al. Alterations of lipid metabolism and gene expression in rat adipocytes during chronic olanzapine treatment. Mol Psychiatry 12, 562–571 (2007). https://doi.org/10.1038/sj.mp.4001948

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  • DOI: https://doi.org/10.1038/sj.mp.4001948

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