Inhibition of autophagy and Hsp90 activity alleviate metabolic and infectious diseases by regulating hepatic lipid deposition and ROS accumulation in zebrafish larvae with hepatobiliary syndrome and/or GCRV-II infection

Hepatobiliary syndrome is caused by the impairment of liver fat metabolism in fish, which leads to the weakening or loss of hepatobiliary function. Also, metabolic hepatobiliary syndrome leads to low immune resistance of diseased fish, which is easily induce fish to be infected with other bacterial or viral diseases. By treating wild-type zebrafish larvae with different concentrations of dexamethasone, we found that dexamethasone induced hepatomegaly, hepatic lipid deposition and reduced survival in zebrafish. In addition, dexamethasone treatment combined with GCRV-II infection aggravated lipid deposition in the liver and impaired the survival of zebrafish larvae. Transcriptome data showed that autophagy signaling pathways and blood pressure regulation pathways are significantly enriched. Furthermore, we treated zebrafish larvae with autophagy inhibitor and HSP90 inhibitor, dexamethasone and GCRV-II infection, then found that the survival of zebrafish larvae was improved, liver lipid deposition was attenuated, and ROS production was greatly reduced. In conclusion, this study provides insights into the regulation of immune metabolism in zebrafish hepatobiliary syndrome and GCRV-II infection, and provides potential molecular targets for the prevention and control of metabolic disease-induced infectious diseases in other cyprinids. To clarify lipid accumulation in the liver of zebrafish, oil red O staining was used to stain zebrafish larvae and photographs were taken under a stereomicroscope. The ROS production of zebrafish larvae was investigated by oxidation-sensitive fluorescent probes, and pictures were taken under a stereoscopic fluorescence microscope. Moreover, key genes in significantly affected signaling pathways were analyzed by transcriptomic analysis.