Effects of 2-ethylhexyl diphenyl phosphate (EHDPP) on glycolipid metabolism in male adult zebrafish revealed by targeted lipidomic analyses

The present study aims to evaluate the effects of 2-ethylhexyldiphenyl phosphate (EHDPP) on glycolipid metabolism in vivo. Adult male zebrafish were exposed to various concentrations (0, 1, 10, 100 and 250 μg/L) of EHDPP for 28 days, and changes in lipid and glucose levels were measured. Results indicated significant liver damages in the 100 and 250 μg/L EHDPP groups, which both exhibited significant decreases in hepatic somatic index (HSI), elevated activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum and liver, as well as hepatocyte vacuolation and nuclear pyknosis. Exposure to 100 and 250 μg/L EHDPP led to significant reductions in serum and liver cholesterol (TC), triglycerides (TGs), and lipid droplet deposition, indicating a significant inhibition of EHDPP on hepatic lipid accumulation. Lipidomic analyses manifested that 250 μg/L EHDPP reduced the levels of 103 lipid metabolites which belong to glycerides (TGs, diglycerides, and monoglycerides), fatty acyles (fatty acids), sterol lipids (cholesterol, bile acids), sphingolipids, and glycerophospholipids, and downregulated genes involved in de novo synthesis of fatty acids (fas, acc, srebp1, and dagt2), while upregulated genes involved in fatty acid β-oxidation (pparα and cpt1). KEGG analyses revealed that EHDPP significantly disrupted glycerolipid metabolism, steroid biosynthesis and fatty acid biosynthesis pathways. Collectively, the results showed that EHDPP induced lipid reduction in zebrafish liver, possibly through inhibiting lipid synthesis and disrupting glycerolipid metabolism. Our findings provide a theoretical basis for evaluating the ecological hazards and health effects of EHDPP on glycolipid metabolism.