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bioRxiv · 10.1101/2022.09.08.507176

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

Singh, R. D.·Wager, J. L.·Scheidl, T. B.·Connors, L. T.·Easson, S.·Callaghan, M. A.·Alatorre-hinojosa, S.·Swift, L. H.·Colarusso, P.·Jadli, A.·SHUTT, T.·Patel, V.·Thompson, J.
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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.

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Singh, R. D., Wager, J. L., Scheidl, T. B., Connors, L. T., Easson, S., Callaghan, M. A., Alatorre-hinojosa, S., Swift, L. H., Colarusso, P., Jadli, A., SHUTT, T., Patel, V., Thompson, J.. 2022-09-08. Potentiation of Adipogenesis by Reactive Oxygen Species is a Unifying Mechanism in the Pro-adipogenic Properties of Bisphenol A and its New Structural Analogues.. https://doi.org/10.1101/2022.09.08.507176

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