Per- and Polyfluoroalkyl Substances (PFASs) Impair Lipid Metabolism in <i>Rana nigromaculata</i>: A Field Investigation and Laboratory Study

Per- and polyfluoroalkyl substances (PFASs) are ubiquitous environmental pollutants, causing environmental threats and public health concerns, but information regarding PFAS hepatotoxicity remains elusive. We investigated the effects of PFASs on lipid metabolism in black-spotted frogs through a combined field and laboratory study. In a fluorochemical industrial area, PFASs seriously accumulate in frog tissues. PFAS levels in frog liver tissues are positively related to the hepatosomatic index along with triglyceride (TG) and cholesterol (TC) contents. In the laboratory, frogs were exposed to 1 and 10 μg/L PFASs, respectively (including PFOA, PFOS, and 6:2 Cl-PFESA). At 10 μg/L, PFASs change the hepatic fatty acid composition and significantly increase the hepatic TG content by 1.33 to 1.87 times. PFASs induce cross-talk accumulation of TG, TC, and their metabolites between the liver and serum. PFASs can bind to LXRα and PPARα proteins, further upregulate downstream lipogenesis-related gene expression, and downregulate lipolysis-related gene expression. Furthermore, lipid accumulation induced by PFASs is alleviated by PPARα and LXRα antagonists, suggesting the vital role of PPARα and LXRα in PFAS-induced lipid metabolism disorders. This work first reveals the disruption of PFASs on hepatic lipid homeostasis and provides novel insights into the occurrence and environmental risk of PFASs in amphibians