Bisphenol A downregulates Akt signaling and inhibits adiponectin production and secretion in 3T3-L1 adipocytes.

AIM The aim of this study was to investigate whether environmental endocrine-disrupting chemicals, bisphenol A (BPA) and BPA-related chemicals, affect adiponectin production and secretion in 3T3-L1 adipocytes and whether BPA acts through Akt signaling. METHODS 3T3-L1 adipocytes were treated for 24 h with BPA at various concentrations (20-80 microM) in serum-deprived medium. The medium was filtered through a 0.2 microm filter. Adiponectin in the infranatants of cell homogenates and in the media was measured using an adiponectin ELISA kit. The levels of Akt and p-Akt in cultures treated for 24 h with or without 80 microM BPA were analyzed by Western blot. RESULTS The control cultures (i.e., BPA was absent during a 24-h treatment period) contained 49.4 microg/mg DNA of adiponectin in the cells and secreted 35.5 microg/mg DNA of adiponectin into the medium. BPA at 80 microM dose-dependently decreased the amounts of intracellular and medium adiponectin by 60% (p<0.01) and 56% (p<0.01), respectively, and decreased the levels of Akt and p-Akt by 46% (p<0.01) and 29% (p<0.01), respectively, compared with the control cultures. Like BPA, bisphenol F (BPF), bisphenol E (BPE), and bisphenol B (BPB) decreased the amounts of intracellular and medium adiponectin. The order of the potential to decrease the amount of intracellular adiponectin was BPB>BPA>BPE>BPF. CONCLUSIONS BPA downregulates Akt signaling and inhibits adiponectin production and secretion in 3T3-L1 adipocytes.