Abstract
Per- and polyfluoroalkyl substances (PFAS) are ubiquitously found in the environment due to their widespread commercial use and high chemical stability. Humans are exposed primarily through ingestion of contaminated water and food and epidemiological studies over the last several decades have shown that PFAS levels are associated with adverse chronic health effects, including cardiometabolic disorders such as hyperlipidemia and non-alcoholic fatty liver disease. Perhaps the most well-established effects, as demonstrated in animal studies and human epidemiological studies, are the metabolic alterations PFAS exposure can lead to, especially on lipid homeostasis and signaling. This altered lipid metabolism has often been linked to conditions such as dyslipidemia, leading to fatty liver disease and steatosis. Western diets enriched in high fat and high cholesterol containing foods may be an important human exposure route of PFAS and may also act as an important modulator of associated toxicities. In fact, the chemical structure of PFAS resemble fatty acids and may activate some of the same signaling cascades critical for endogenous metabolism. In this review we aim to outline known dietary exposure sources of PFAS, describe the detrimental metabolic health effects associated with PFAS exposure, and focus on studies examining emerging interaction of dietary effects with PFAS exposure that further alter the dysregulated metabolic state.
Highlights
Per- and polyfluoroalkyl substances (PFAS) have become a popular component added to numerous industrial and consumer products used in everyday life (Center for Disease Control and Prevention, 2017)
The PFAS family of synthetic chemicals are pervasive throughout the environment and exposure is known to occur via multiple routes, including indoor dust and air, drinking water, and diet
PFAS exposure is associated with hyperlipidemia in humans, while animal studies commonly report hypolipidemia
Summary
Per- and polyfluoroalkyl substances (PFAS) have become a popular component added to numerous industrial and consumer products used in everyday life (Center for Disease Control and Prevention, 2017). Epidemiological studies have shown that humans exposed to very high levels of PFAS, most frequently PFOS and PFOA, are positively associated with increased cholesterol and other serum lipids (Olsen and Zobel, 2007; Sakr et al, 2007; Costa et al, 2009; Steenland et al, 2009; Frisbee et al, 2010). Studies involving populations exposed to PFAS-contaminated water sources revealed strong associations between serum concentrations of PFOS and PFOA with elevated ALT levels, a surrogate marker for fatty liver disease In a 2019 study analyzing data from NHANES for 2005–2014, it was demonstrated that obesity in both males and females altered the cross-sectional associations of different PFAS with plasma lipid concentrations (Jain and Ducatman, 2019a) In this study, both PFOA and PFNA were positively associated with total cholesterol levels for obese males, but not for non-obese males. The impact of dietary modulation on PFAS toxicity in humans remains a largely unexplored area of research and warrants further investigation to better understand the interactive effects of diet and PFAS toxicity
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