Fatty liver disease is common in cultured yellow catfish as a result of high fat contents in feeds. However, little is known about the mechanism by which the excessive deposition of liver fat causes fatty liver disease. Hybrid yellow catfish (Pelteobagrus fulvidraco♀ × P. vachelli♂) were fed a high-fat diet (HFD) or a normal-fat diet (NFD) for 60 days. Compared with the NFD group, the HFD group showed lower growth performance, higher hepatosomatic and viscerosomatic indexes, increased hepatic triglyceride and cholesterol contents, and more and larger lipid droplets in liver tissue. Whole transcriptome mRNA libraries and microRNA libraries from fish in the NFD and HFD groups were constructed by high-throughput sequencing. Twelve miRNAs were differentially expressed (DE) between the HFD and NFD groups. Seven negatively correlated DE miRNA–DE mRNA pairs were selected, and the expression patterns of both were confirmed using qRT-PCR. Hybrid yellow catfish showed mediated oxidative degradation of liver glucose and fatty acid peroxidation, regulation of antioxidant enzyme activity, and various immune and inflammatory responses to fat deposition and stress. These findings have important biological significance for protecting the liver against stress, as well as economic significance for establishing healthy aquaculture conditions.
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