Fig. 8

Hypothesized mechanisms linking western diet and BPA exposure to oxidative stress and PON1 activity changes based on the observations in this study and supported by mechanistic knowledge from existing literature (Rani et al., 2016; Tan et al., 2018; Gassman, 2017). The western diet likely caused a metabolic shift towards a fatty acid-based energy metabolism, which was increased by BPA exposure. The increased fatty acid-based energy metabolism caused increased oxidative stress. Additionally, BPA independently contributed to oxidative stress by lowering antioxidant activity and producing reactive oxygen species. The increased oxidative stress likely triggered the increased PON1 activity as an antioxidant response. Although we have not direct evidence for a link with lipid transport, PON1 is known to be associated to lipid transport through HDL and is influenced by regulators of lipid metabolism. These factors are therefore also likely to contribute to the PON1 response caused by the western diet (Blatter Garin et al., 2006; Camps et al., 2012; Escolà-Gil et al., 2011).