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Lack of the serotonin transporter in mice reduces locomotor activity and leads to gender-dependent late onset obesity

International Journal of Obesity volume 34, pages 701–711 (2010)Cite this article

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Abstract

Objective:

Mice deficient of the serotonin transporter (5-HTT ko) mice have a reduced brain serotonin content and develop late-onset obesity. To elucidate the pathophysiology of this obesity, we analyzed the expression of the interrelated weight-regulatory molecules: brain-derived neurotrophic factor (BDNF) and leptin receptor (LR) in brain areas associated with nutrition and activity.

Research Design and Methods:

We investigated feeding behavior, physical activity and metabolic parameters of 5-HTT ko and wild-type mice and measured the expression of BDNF and LR in brain areas associated with nutrition and activity using quantitative real-time PCR. The influence of age, gender and fasting was analyzed.

Results:

Male 5-HTT ko mice developed obesity without hyperphagia from the age of 5 months. Physical activity was reduced in old male, but not old female, 5-HTT ko mice. The BDNF gene expression in frontal cortex was elevated in young, but reduced in old 5-HTT ko mice. Fasting failed to increase the BDNF gene expression in frontal cortex of young 5 HTT ko mice and in the hypothalamus in old 5-HTT ko mice. The fasting-induced hypothalamic increase of LR was absent in both young and old 5-HTT ko mice.

Conclusions:

We propose that low brain serotonin level due to the 5-HTT ko genotype leads to reduced physical activity and low BDNF, which together with the lack of fasting-induced hypothalamic BDNF and LR production results in late-onset obesity. Although lack of the 5-HTT is a genetic vulnerability factor for obesity, female gender is protective.

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Acknowledgements

We thank L Biko, H Brünner, B Dekant, B Gado and S Mildner for technical assistance and A Spahn for help with the statistical assessments. The study was supported by Deutsche Forschungsgemeinschaft (Le629/4–2 and SFB 581/B9 to K.P.L.) and by intramural funds of the Universities of Würzburg and Lübeck.

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Authors and Affiliations

  1. Department of Neurology, University of Würzburg, Würzburg, Germany

    N Üçeyler, F Palm, C Vogel & C Sommer

  2. Department of Internal Medicine I, University Hospital of Schleswig-Holstein, Lübeck, Germany

    M Schütt & M Meier

  3. Department of Psychiatry, Molecular and Clinical Psychobiology, University of Würzburg, Würzburg, Germany

    A Schmitt, K-P Lesch & R Mössner

  4. Department of Psychiatry, University of Bonn, Germany

    R Mössner

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  1. N Üçeyler
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Correspondence to N Üçeyler.

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Üçeyler, N., Schütt, M., Palm, F. et al. Lack of the serotonin transporter in mice reduces locomotor activity and leads to gender-dependent late onset obesity. Int J Obes 34, 701–711 (2010). https://doi.org/10.1038/ijo.2009.289

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