Hepatic lipid metabolic dysregulation mediates fluxapyroxad-induced hepatotoxicity: Insights from multi-omics profiling.

Fluxapyroxad (FLU), a widely used succinate dehydrogenase inhibitor (SDHI) fungicide, can enter aquatic environments and pose potential risks to aquatic organisms. This study investigated the hepatotoxic effects of long-term FLU exposure in adult zebrafish exposed to 0, 30, 60, and 90 μg/L FLU for 28 days. High-dose (90 μg/L) exposure significantly reduced body weight, increased liver weight, and induced hepatic vacuolization and reduced glycogen storage in histological analysis. Transcriptomic analysis of the high-dose group revealed significant upregulation of lipid metabolism-related genes (ldlr, lpin1, apoc2), enriched in PPAR signaling and non-alcoholic fatty liver disease pathways; lipidomic profiling showed widespread lipid alterations (especially phosphatidylcholine species), with glycerophospholipid metabolism as the most affected pathway, and 11 differential lipid species including PC(18:0/16:0) and TG(20:0/14:0/14:0) were identified as candidates. Integrated multi-omics analysis demonstrated that high-dose FLU exposure triggered hepatic lipid metabolic disorders via dysregulated expression of genes involved in lipid synthesis, transport and degradation. These findings reveal the mechanism of FLU-induced hepatotoxicity, and provide reference for identifying FLU-responsive hepatic differential lipids, as well as ecological risk assessment of FLU and related SDHI fungicides in aquatic systems.