The environmental obesogen bisphenol A promotes adipogenesis by increasing the amount of 11β-hydroxysteroid dehydrogenase type 1 in the adipose tissue of children.

Abstract

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. 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. 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. 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. 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.