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No evidence for a direct effect of clozapine on fat-cell formation and production of leptin and other fat-cell-derived factors

Molecular Psychiatry volume 8, pages 258–259 (2003)Cite this article

Atypical neuroleptics are known to induce substantial weight gain in a considerable proportion of patients within a few months of treatment.1 Among the currently available atypical antipsychotic drugs clozapine appears to have the greatest weight-increasing potential.2 To understand the underlying mechanisms, we examined whether clozapine has an effect on human adipocyte development and specific functions of mature fat cells such as glucose transport, lipolysis, and production and secretion of leptin, interleukin-6 (IL-6) and plasminogen activator inhibitor-1 (PAI-1). The results of our in vitro study do not provide evidence for a direct effect of clozapine on these functions arguing that central rather than peripheral mechanisms may induce weight gain and the metabolic disturbances under clozapine treatment.

Little is currently known about the mechanisms of weight gain by atypical neuroleptics. One common hypothesis is that patients experience a lower suppression of appetite after meals indicating that the perception of satiety may be impaired.1 Interestingly, clozapine was recently found to increase serum leptin levels within days after initiation of treatment.3,4 To get more insight into the pathophysiology of clozapine-induced weight gain, we studied the effect of the drug on fat cell formation and selected metabolic and secretory functions of human adipose tissue.

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References

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Authors and Affiliations

  1. German Diabetes Research Institute, Heinrich-Heine-University Düsseldorf, Auf'm Hennekamp 65, Düsseldorf, 40225, Germany

    H Hauner, K Röhrig & Th Skurk

  2. Department of Child and Adolescent Psychiatry of the University of Marburg, Clinical Research Group, Marburg, 35033, Germany

    J Hebebrand

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  1. H Hauner
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  2. K Röhrig
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  3. J Hebebrand
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  4. Th Skurk
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Correspondence to H Hauner.

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Hauner, H., Röhrig, K., Hebebrand, J. et al. No evidence for a direct effect of clozapine on fat-cell formation and production of leptin and other fat-cell-derived factors. Mol Psychiatry 8, 258–259 (2003). https://doi.org/10.1038/sj.mp.4001246

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