Exploring the effects of PFAS exposure on adult blood lipids: evidence based on epidemiology, toxicogenomic data mining and molecular docking

Le résumé fourni par la source

Previous studies remain controversial regarding the relationship between Per- and polyfluoroalkyl substances (PFAS) exposure and blood lipids, and the toxicological mechanisms are poorly studied. This research focused on exploring the relationships and underlying mechanisms through which PFAS exposure leads to dyslipidemia in the adults. We analyzed data from 9,781 adults participating in the National Health and Nutrition Examination Survey (NHANES) 2003 to 2020. Weighted Quantile Sum (WQS) and Bayesian Kernel Machine Regression (BKMR) models were employed to assess the correlations between PFAS mixtures and lipid parameters, including low-density lipoprotein (LDL), total cholesterol (TC), triglycerides (TG), and high-density lipoprotein (HDL). Sex-stratified multivariable regression models were constructed to assess potential sex-specific variations. Toxicogenomic data mining and Molecular docking were used to identify the molecular pathways linking PFAS exposure to lipid metabolism alterations. Epidemiological investigations have shown that an increase in PFAS mixture concentration in the general population is significantly correlated with an increase in LDL, TC, and TG levels, as well as a decrease in HDL levels. In the sex-stratified analysis, PFAS exposure was negatively correlated with HDL in males and positively correlated with HDL in females; however, no significant sex differences were detected in LDL, TC, or TG levels. Toxicogenomic data mining shows that genes such as apolipoprotein E (APOE) may be closely related to PFAS exposure and dyslipidemia, and pathways such as the peroxisome proliferator‑activated receptor (PPAR) signaling pathway play important roles in this process. This study indicate that PFAS exposure is associated with sex-specific modifications in lipid profiles, potentially implicating lipid metabolism pathways. These results underscore the necessity for further investigation into the mechanisms underlying PFAS-induced dyslipidemia and the development of appropriate interventions.

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