Effects of sublethal concentration of metamifop on hepatic lipid metabolism in adult zebrafish (Danio rerio)

Metamifop (MET) is an effective herbicide that has been extensively used in paddy fields. Previous research demonstrated that MET was highly toxic to zebrafish embryos, and this threat has caused great concern; moreover, 0.40 mg/L MET elevated the hepatosomatic index (HSI) in adult zebrafish without lethal effect after 21 d of exposure. In this study, we further determined the detailed impacts of MET on adult zebrafish at sublethal concentrations (0.025, 0.10 and 0.40 mg/L). We found that 0.40 mg/L MET caused liver injury by increasing the activity of aspartate aminotransferase and alanine aminotransferase in plasma, the content of interleukin-1β, IL-6, tumor necrosis factor-α, and mRNA expression level of genes associated with inflammatory response in liver of adult zebrafish. The hepatic triglyceride (TG), free fatty acid and fatty acid synthase levels were significantly elevated in 0.40 mg/L MET-treated group (1.55-, 2.20- and 2.30-fold, respectively), and the transcript of lipid accumulation-related genes (fabp10, fas, acc, chrebp, dagt2 and agpat4) were upregulated. Meanwhile, the total cholesterol content was decreased by 0.48-fold, bile acid level was increased by 2.44-fold, and levels of cholesterol metabolism-related genes (apoa-1a, hmgcra, cyp51, dhcr7 and cyp7a1) were increased, suggesting cholesterol metabolism disorder occurred in zebrafish. Furthermore, analysis of lipidomics revealed that 0.40 mg/L MET significantly increased the abundance of 91 lipids, which mainly belonged to TG lipid class and were enriched in pathways of glycerolipid metabolism, cholesterol metabolism, etc. These results suggested that MET exposure at sublethal concentrations would induce hepatic inflammation and lipid metabolism disorders in adult zebrafish.