Dietary exposure to hexafluoropropylene oxide dimer acid (HFPO-DA ammonium salt, GenX) alters hepatic sphingomyelin and phosphatidylcholine metabolism in Nile Tilapia (Oreochromis niloticus)

HFPO-DA ammonium salt (GenX) is used to replace the environmentally persistent perfluorooctanoic acid (PFOA), but its effects on fish lipid metabolism remain poorly understood. This study investigated the impact of dietary GenX exposure (0.73 and 3.10 mg/Kg of feed, measured concentrations) on hepatic lipid metabolism and oxidative stress in juvenile male Nile tilapia (5.32 ± 1.60 g) over 28 days. While fish increased body weight over time, there were no differences in weight gain among treatments. There were no changes in hepatic glycerol levels with either dose of feed, while triglycerides decreased in the low-dose group. Using an untargeted Liquid Chromatography with Tandem Mass Spectrometry (LC-MS/MS) lipidomic approach (a technique for broad profiling of lipid species), we detected 169 lipids in the liver, and 25 lipids altered their abundance following treatment with GenX. Fish fed with 0.73 mg/Kg GenX had increased levels of sphingomyelins (4), diacylglycerols (4), and triglycerides (1), and decreased levels of phosphatidylcholines (6), sphingomyelins (2), ceramides (1), and phosphatidylinositol (1). In the high-dose group, phosphatidylcholines (5), lysophosphatidylcholine (3), fatty acids (2), and ceramides (1) had their levels increased compared to the control. GenX increased the hepatic expression of lipid-related transcripts; elovl5 mRNA levels were increased in fish with both feeding regimes, while the expression levels of aco1 and fas increased at 3.10 mg/Kg. The expression of oxidative stress-related genes gpx and cat decreased at 0.73 and 3.10 mg/Kg, respectively, suggestive of depleted antioxidant defense enzymes. Our study sheds light on how dietary GenX exposure may affect aquatic organisms, contributing to its risk assessment.