Nafion by-product 2 disturbs lipid homeostasis in zebrafish embryo

As a novel polyfluoroalkyl substance, Nafion by-product 2 (Nafion BP2) has been detected widely in environmental matrix as well as human samples. However, its toxicity remains poorly recognized. Here, we investigated the toxic effects of Nafion BP2 by use of zebrafish model and highlighted its toxicity on lipid homeostasis. Large sized-lipid droplets (LDs) have been revealed to gather in pericardium and anterior yolk sac region of zebrafish larvae by Oil Red O staining after a 120 h Nafion BP2 exposure. Meanwhile, the total cholesterol (TC) concentrations were significantly disrupted. Lipidomic analysis uncovered a dramatical alterations on lipid profiles. Significant reductions were observed for a set of lipids including phosphatidylinositol (PI), phosphatidylcholine (PC), phosphatidylethanolamine (PE), sphingolipid (SM) and triglyceride (TG) in zebrafish. Transcriptome analyses further confirmed genes involved in LDs biosynthesis, lipid transportation and lipid metabolism, were significantly disrupted. Especially for APOA4 and CIDEC genes, fold changes (Log2 FC) of gene expression level by up to 17.8 and 3.5, respectively, were observed. Together, these findings demonstrated the disturbance of Nafion BP2 on lipid homeostasis of zebrafish and provided an unprecedented insight into the health risk assessments of emerging fluorochemicals.