Environmental exposure to low-dose perfluorohexanesulfonate promotes obesity and non-alcoholic fatty liver disease in mice fed a high-fat diet

Perfluorohexanesulfonate (PFHxS) is one of the most prevalent perfluoroalkyls. It is widely distributed in both abiotic and biotic environments because of its prevalence and bioaccumulative properties. Exposure to PFHxS has been associated with the higher serum liver functions associated with steatosis in obese people. This study explores the impact of chronic exposure to low-dose PFHxS on predisposition to non-alcoholic fatty liver disease (NAFLD) as well as on metabolic functions in diet-induced obese mice. Results showed that 12-week exposure to PFHxS at a dose of 450 mu g/L through drinking water significantly promoted obesity and metabolic syndrome in male C57 mice fed a high-fat diet. The PFHxS exposure markedly aggravated hepatic symptoms resembling NAFLD and caused systematic metabolic disorders as well as gut dysbiosis in the obese mice. Key genes of hepatic lipid metabolism, inflammation, and fibrosis were strongly altered, while gut microflora that have been associated with obesity and pathogenesis of NAFLD, including the Bacteroides/Firmicutes ratio, Desulfovibrio, Mucispirillum, and Akkermansia, were significantly affected by the PFHxS exposure. The findings of this study suggest that environmental PFHxS exposure is a tangible risk factor for metabolic diseases such as NAFLD, especially among obese individuals.