The Mixture of Bisphenol-A and Its Substitutes Bisphenol-S and Bisphenol-F Exerts Obesogenic Activity on Human Adipose-Derived Stem Cells

Bisphenol A (BPA) and its substitutes, bisphenol F (BPF) and S (BPS), have previously shown in vitro obesogenic activity. This study was designed to investigate their combined effect on the adipogenic differentiation of human adipose-derived stem cells (hASCs). Cells were exposed for 14 days to an equimolar mixture of bisphenols (MIX) (range 10 nM-10 mu M). Oil Red staining was used to measure intracellular lipid accumulation, quantitative real-time polymerase chain reaction (qRT-PCR) to study gene expression of adipogenic markers (PPAR gamma, C/EBP alpha, LPL, and FABP4), and Western Blot to determine their corresponding proteins. The MIX promoted intracellular lipid accumulation in a dose-dependent manner with a maximal response at 10 mu M. Co-incubation with pure antiestrogen (ICI 182,780) inhibited lipid accumulation, suggesting that the effect was mediated by the estrogen receptor. The MIX also significantly altered the expression of PPAR gamma, C/EBP alpha, LPL, and FABP4 markers, observing a non-monotonic (U-shaped) dose-response, with maximal gene expression at 10 nM and 10 mu M and lesser expression at 1 mu M. This pattern was not observed when bisphenols were tested individually. Exposure to MIX (1-10 mu M) also increased all encoded proteins except for FABP4, which showed no changes. Evaluation of the combined effect of relevant chemical mixtures is needed rather than single chemical testing.

Automated summary

This study investigated the combined effect of bisphenol A (BPA) and its substitutes, bisphenol F (BPF) and S (BPS), on the adipogenic differentiation of human adipose-derived stem cells (hASCs). The researchers found that the mixture of bisphenols promoted lipid accumulation in the cells in a dose-dependent manner, with a maximal response at 10 μM. The effect was mediated by the estrogen receptor, and the mixture also altered the expression of adipogenic markers in a non-monotonic dose-response pattern.