Increasing PFAS concentrations in human serum correlate with elevated blood lipid levels

Per- and polyfluoroalkyl substances (PFAS) are a large group of synthetic chemicals which have been detected in the blood of >99% people worldwide. Currently, certain PFAS are linked to elevated cholesterol levels in humans, but few studies have assessed changes in specific lipid species to assess mechanistic changes. In this study, 78 serum samples were attained from 49 participants exposed to elevated PFAS through drinking water and 29 occupationally exposed firefighters. PFAS serum concentrations were initially assessed, and drinking water exposure participants illustrated higher PFAS serum levels than both the firefighters and national median values from the National Health and Examination Survey (NHANES). Participants were then regrouped for lipidomic analyses using their summed serum concentration for 7 PFAS (Σ7 PFAS). Thirty-four participants in our study had Σ7 PFAS concentrations ≥20 ng mL^-1, a level that has been associated with increased risk of dyslipidemia, thyroid dysfunction and cancer according to the National Academies PFAS Exposure Guidance Report. Statistical analyses revealed that 24 lipids out of 387 detected in all participants were significantly higher in participants with Σ7 PFAS values ≥20 ng mL^-1. Triglycerides and phosphatidylethanolamines specifically represented 62.5% of these 24 lipids, suggesting alteration of cellular membrane structures and energy storage. A statistical assessment on the female-only samples from the drinking water cohort was also performed to reduce bias due to sex, age and occupational covariates and further validated these trends. This study therefore illustrates increased serum PFAS concentrations correlate with elevated lipid species and molecular pathway alterations in highly exposed individuals.