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

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 3 T 3 F 442 A preadipocytes by fluorometric and radiometric methods. Gene expression was assessed by real‐time RT ‐ PCR in human adipocytes and in 3 T 3 F 442 A 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 ( FABP 4, CD 36, GLUT 1, and phosphoenolpyruvate carboxykinase), as did rosiglitazone treatment. Long‐term serotoninergic stimulation of cultured 3 T 3 F 442 A 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.