Environmental contaminants impair liver metabolism, leading to NAFLD

Exposure to environmental contaminants (ECs), particularly perfluorinated alkyl substances (PFAS), seems to disrupt bile acid and lipid metabolism, both key hepatic metabolic pathways that are known to be dysregulated in nonalcoholic fatty liver disease (NAFLD), a recent study has found. Such an effect seems to be more pronounced in women.

In a cohort of 105 patients with well-characterized NAFLD, EC exposure was measured by subjecting serum samples to various quantitative, analytical assays, while the liver metabolome was assessed through a biopsy.

Gradient-boosted decision tree models showed that the presence of PFAS in the serum correlated positively with liver fat content and insulin resistance. For example, perfluorooctanesulfonic acid (PFOS) and methylparabens were associated positively with nonalcoholic steatohepatitis, while PFOS was significantly linked with hepatic fibrosis.

Moreover, such interactions between the liver metabolome, EC exposure, and clinical variables associated with NAFLD were stronger in women than in men, particularly in terms of PFAS-associated upregulation of bile acids, ceramides, and triglycerols. The correlation between EC exposure and disrupted glucose metabolism was likewise more pronounced in women.

“There is increasing evidence that specific ECs such, as per- and polyfluoroalkyl substances, contribute to the progression of NAFLD. However, it is poorly understood how these chemicals impact human liver metabolism. Here we show that human exposure to PFAS impacts liver metabolic processes associated with NAFLD, and does so in a sexually-dimorphic manner,” the researchers said.