Bisphenol A, but not Bisphenol S, exposure increases lipid deposition by acting on the PI3K pathway in vivo

Abstract

Bisphenol A (BPA) is an endocrine disrupter present in many daily products including food and beverage packaging. BPA exposure has been linked to many disorders in humans including cancer, neurological disorders, diabetes and obesity and has therefore been declared toxic and a partial ban is in effect in several countries. Recently the plastic industry has come with a bisphenol analog as a substitute for BPA in BPA free products: BPS. However to date, little is known regarding the toxicity of BPS in vivo. In this study, we used the zebrafish as a vertebrate model to understand the mechanism of action of BPA and BPS in lipid usage during embryogenesis. Zebrafish embryos exposed to the extreme low dose 1 nM BPA (over 6,000‐fold lower than the accepted human daily exposure), have a 65% increase in lipid deposition. Interestingly, BPS exposure, at the same concentration, has no effect on lipid deposition. BPA is classified as an estrogenic compound however, pharmacological blockage of the nuclear estrogen receptors does not suppress the induced lipid deposition. To identify which pathway might be involved in this increased lipid deposition, we performed a full embryo lipidomic analysis. This revealed that BPA exposed embryos had a dramatic increase of diacylglycerol (DAG) and Phosphatidylinositol (PI) lipids. Strikingly, lipidomic analysis of BPS exposed embryos showed a decrease of DAGs and PIs. This is the first study to demonstrate a phenotypical difference between BPA and BPS at similar doses. Double exposure of BPA and LY294002, a strong inhibitor of phosphoinositide 3‐kinases, abolishes the BPA induced increase in lipid deposition and lipid usage. At the molecular level, BPA exposure increases the expression of key enzymes of the PI3K pathway such as: cdipt, plcb3, vps34p and p110. Our study allows us to propose a model in which BPA, but not BPS, at very low concentration can activate the PI3K pathway leading to an accumulation of lipid during embryogenesis in an estrogen receptors independent manner. Our results confirm that, at least in terms a of lipid usages, BPS is safer than BPA exposure and support the ban on BPA from consumer merchandise.Support or Funding InformationThis project was supported by an Australian Diabetes Research Trust (DART) research grant to YGThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.