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Oxidation of high doses of serotonin favors lipid accumulation in mouse and human fat cells

Authors

  • Sandra Grès,

    1. Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université de Toulouse, UPS, Toulouse, France
    2. Institut National de la Santé et de la Recherche Médicale, Toulouse, France
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  • Sarah Canteiro,

    1. Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université de Toulouse, UPS, Toulouse, France
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  • Josep Mercader,

    1. Institut National de la Santé et de la Recherche Médicale, Toulouse, France
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  • Christian Carpéné

    Corresponding author
    1. Institut National de la Santé et de la Recherche Médicale, Toulouse, France
    • Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université de Toulouse, UPS, Toulouse, France
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Correspondence: Dr. Christian Carpéné, INSERM U 1048, Bat L4, CHU Rangueil, 31432 Toulouse cedex 4, France

E-mail: christian.carpene@inserm.fr

Abstract

Scope

The ingestion of serotonin-rich food (bananas, chocolate) increases 5-hydroxytryptamine (5-HT) in blood and its corresponding oxidation products in urines but without direct central consequences since the neurotransmitter does not easily cross the blood-brain barrier. However, there are numerous peripheral effects of serotonin, and recently, 5-HT aldehydic oxidation products have been demonstrated to behave as ligands of peroxisome proliferator-activated receptor γ (PPAR-γ). Since this nuclear factor manages lipid handling by adipose tissue, the response of fat cells to 5-HT exposure needed further investigation.

Methods and results

Serotonin oxidation was studied on human adipose tissue homogenates and mouse 3T3F442A preadipocytes by fluorometric and radiometric methods. Gene expression was assessed by real-time RT-PCR in human adipocytes and in 3T3F442A after mid- and long-term exposure to 5-HT while triacylglycerols and proteins were assessed by spectrophotometry. Six-hour exposure of human adipocytes to 250 μM 5-HT increased gene expression of lipid-binding proteins, glucose carriers, and enzymes of triacylglycerol synthesis (FABP4, CD36, GLUT1, and phosphoenolpyruvate carboxykinase), as did rosiglitazone treatment. Long-term serotoninergic stimulation of cultured 3T3F442A preadipocytes by 100–250 μM 5-HT enhanced fat storage and upregulation of PPAR-γ-responsive genes, in a manner sensitive to MAO- or PPAR-γ inhibition. Our observations suggest an unpredicted peripheral effect of serotonin on adipose tissue that depends on its amine oxidation.

Conclusion

Besides being centrally active on eating behavior, 5-HT may promote PPAR-γ activation and subsequent lipogenic effects in fat cells, raising the interest to consider its level in future diet formulations.

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