A novel model construction of lithocholic acid-induced cholestasis and transcriptome analysis in snakehead fish (Channa argus)

The snakehead fish (Channa argus) is very susceptible to hepatobiliary syndrome during the farming, usually accompanied by abnormal function of the liver, gallbladder and intestine. In this study, we aimed to establish a lithocholic acid (LCA)-induced cholestasis model to confirm the model by liver transcriptome analysis, and to explore the effects of dietary supplementation with 0, 0.05%, 0.1%, 0.2%, 0.4% and 0.6% LCA on serum biomarkers, histopathological and the mRNA expressions levels of bile acid metabolism-related genes in C. argus. Biochemical analysis results showed that the levels of ALT, AST, TBA and ALP in serum were markedly increased (P < 0.05) in C. argus with cholestasis induced by 0.2%, 0.4% and 0.6% LCA. In this study, 101.09 GB of clean data a total of 83,513 unigenes and 107,325 transcripts was obtained by liver transcriptome sequencing of C. argus using the Illumina HiSeq XTen/NovaSeq 6000 platforms. A total of 206 differentially expressed genes (DEGs), i.e., 112 up-regulated DEGs and 94 down-regulated DEGs, were identified between the control and LCA treatment groups based on the liver transcriptome analysis. Notably, the key bile acid metabolism-related DEGs, such as bsep, shp, fxr, mrp2, mrp3, mrp4, cyp7a1, cyp8b1, cyp27a1 and hmgcr were found in the liver transcriptome. Overall, this study is the first time to investigate the establishment of an LCA-induced cholestasis model in aquatic animals, as evidenced by the deaths of fish, serum biomarkers, and the liver histopathological status. These data help our comprehension of the pattern of bile acid metabolism in aquatic animals, and provide a certain insight into treatments for hepatobiliary syndrome in C. argus

Automated summary

This study established an LCA-induced cholestasis model in snakehead fish, investigated the effects of different concentrations of LCA on serum biomarkers, histopathological changes, and mRNA expressions of bile acid metabolism-related genes through liver transcriptome analysis. Key genes related to bile acid metabolism were identified in the liver transcriptome of C. argus with cholestasis induced by LCA.