title: Oxidation of high doses of serotonin favors lipid accumulation in mouse and human fat cells.
abstract: METHODS
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université de Toulouse, UPS, Toulouse, France.
authors: Sandra
authors: S
authors: Grès
authors: Sarah
authors: S
authors: Canteiro
authors: Josep
authors: J
authors: Mercader
authors: Christian
authors: C
authors: Carpéné
mesh_terms: D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism*; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000328:Adult; D000818:Animals; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects*; D051379:Mice; D008875:Middle Aged; D010084:Oxidation-Reduction; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D012701:Serotonin / Q000008:administration & dosage* / Q000378:metabolism*
chemical_list: D018955:CD36 Antigens; C493410:FABP4 protein, human; D050556:Fatty Acid-Binding Proteins; D051272:Glucose Transporter Type 1; D047495:PPAR gamma; C495679:Slc2a1 protein, rat; D012701:Serotonin