Lipid Metabolic Disorder Induced by Pyrethroids in Nonalcoholic Fatty Liver Disease of Xenopus laevis

Pyrethroids, an effective and widely used class of pesticides, have attracted considerable concerns considering their frequent detection in environmental matrices. However, their potential health risks to amphibians remain unclear. In our study, female Xenopus laevis were exposed to 0, 0.06, and 0.3 μg/L typical pyrethroid, cis-bifenthrin (cis-BF), for 3 months. Elevated activities of both aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were observed, indicating an ongoing liver injury. Furthermore, exposure to cis-BF led to hyperlipidemia and lipid accumulation in the liver of Xenopus. The targeted lipidomic analysis further revealed that treatment with cis-BF perturbed liver steroid homeostasis, as evidenced by the enriched lipids in the steroid biosynthesis pathway. Consistent with the targeted lipidomic result, treatment with cis-BF changed the liver transcriptome profile with induction of 808 and 1230 differentially expressed genes. Kyoto Encyclopedia of Genes and Genomes analysis underlined the adverse effects of cis-BF exposure on steroid biosynthesis, primary bile acid biosynthesis, and the PPAR signaling pathway in the Xenopus liver. Taken together, our study revealed that exposure to cis-BF at environmentally relevant concentrations resulted in lipid metabolic disorder associated with nonalcoholic fatty liver disease of X. laevis, and our results provided new insight into the potential long-term hazards of pyrethroids.