Potentiation of Adipogenesis by Reactive Oxygen Species is a Unifying Mechanism in the Pro-adipogenic Properties of Bisphenol A and its New Structural Analogues.

Abstract

AimsStructural analogues of bisphenol A (BPA), including BPS and BPF, are emerging environmental toxicants as their presence in the environment is rising since new regulatory restrictions were placed on BPA-containing infant products. The adipogenesis-enhancing effect of bisphenols may explain the link between human exposure and metabolic disease; however, underlying molecular pathways remain unresolved. ResultsExposure to BPS, BPF, BPA or ROS generators enhanced lipid droplet formation and expression of adipogenic markers after induction of differentiation in adipose-derived progenitors isolated from mice. RNAseq analysis in BPS-exposed progenitors revealed modulation in pathways regulating adipogenesis and responses to oxidative stress. ROS was higher in bisphenol-exposed cells, while co-treatment with antioxidants attenuated adipogenesis and abolished the effect of BPS. There was a loss of mitochondria membrane potential in BPS-exposed cells and mitochondria-derived ROS contributed to potentiation of adipogenesis by BPS and its analogues. Male mice exposed to BPS during gestation had higher whole-body adiposity, as measured by TD-NMR, while postnatal exposure had no impact on adiposity in either sex. InnovationThese findings support existing evidence showing a role for ROS in regulating adipocyte differentiation and are the first to highlight ROS as a unifying mechanism that explains the pro-adipogenic properties of BPA and its structural analogues. ConclusionROS act as signaling molecules in the regulation of adipocyte differentiation and mediate bisphenol-induced potentiation of adipogenesis.