title: The environmental obesogen bisphenol A promotes adipogenesis by increasing the amount of 11β-hydroxysteroid dehydrogenase type 1 in the adipose tissue of children.
abstract: BACKGROUND
  Bisphenol A (BPA) is considered as an environmental obesogen. The enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) converts the inactive hormone cortisone to the active hormone cortisol in adipose tissues and promotes adipogenesis.
  
  
  OBJECTIVE
  To examine whether environmentally relevant concentrations of BPA could increase the expression of 11β-HSD1, as well as that of the adipogenesis-related genes peroxisome proliferator-activated receptor-γ (PPAR-γ) and lipoprotein lipase (LPL), in the adipose tissue of children.
  
  
  METHODS
  Omental fat biopsies were obtained from 17 children (7 boys and 10 girls between 3 and 13 years of age) undergoing abdominal surgery. The effects of BPA (10 nM, 1 μM, and 80 μM) on 11β-HSD1, PPAR-γ and LPL mRNA expression, and 11β-HSD1 enzymatic activity in adipose tissue and adipocytes were assessed in vitro. Moreover, the effects of carbenoxolone (CBX), an 11β-HSD1 inhibitor, or RU486, a glucocorticoid (GC) receptor antagonist, on 11β-HSD1, PPAR-γ and LPL mRNA expression were assessed in human visceral preadipocytes and adipocytes.
  
  
  RESULTS
  BPA, even at the lowest concentration tested (10 nM), increased the mRNA expression and enzymatic activity of 11β-HSD1 in the omental adipose tissue samples and the visceral adipocytes. Similar effects on PPAR-γ and LPL mRNA expression and lipid accumulation were observed in the adipocytes. CBX treatment inhibited the stimulatory effects of BPA (at 10 nM) on PPAR-γ and LPL mRNA expression, whereas RU486 inhibited 11β-HSD1 mRNA expression in the adipocytes.
  
  
  CONCLUSIONS
  BPA, at environmentally relevant levels, increased the mRNA expression and enzymatic activity of 11β-HSD1 by acting upon a GC receptor, which may lead to the acceleration of adipogenesis.
authors.affiliation: Department of Children's Health Care, Nanjing Children's Hospital Nanjing Medical University, Nanjing, China.
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: B
authors.initials: B
authors.lastname: Sun
authors.forename: M
authors.initials: M
authors.lastname: Hou
authors.forename: X
authors.initials: X
authors.lastname: Pan
authors.forename: X
authors.initials: X
authors.lastname: Li
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000187:drug effects / Q000378:metabolism*; D050156:Adipogenesis / Q000187:drug effects*; D000273:Adipose Tissue / Q000201:enzymology; D000293:Adolescent; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D002648:Child; D002675:Child, Preschool; D002681:China / Q000453:epidemiology; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006801:Humans; D008297:Male; D009765:Obesity / Q000201:enzymology / Q000453:epidemiology / Q000517:prevention & control*; D009852:Omentum / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology*; D040521:Subcutaneous Tissue / Q000378:metabolism; D000098826:Bisphenol A Compounds
chemical_list: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D001559:Benzhydryl Compounds; D016166:Free Radical Scavengers; D047495:PPAR gamma; D010636:Phenols; C468386:HSD11B1 protein, human; C006780:bisphenol A; D000098826:Bisphenol A Compounds