Abstract:Excessive accumulation of lipid seriously harms fish health and is a common nutritional disease in cultured fish. So far, the formation and regulation mechanism of fatty liver in fish is not clear. To clarify the protective effect of Saikosaponin a (SSa) on the liver of fish, a model of hepatocyte steatosis of hybrid grouper (Epinephelus lanceolatus♂ × Epinephelus fuscoguttatus♀) induced by 20% lipid emulsions (LE) with 2ml/L was established, and the effects of SSa on hepatocyte survival rate, intracellular lipid content, mitochondrial function, lipid metabolism and immune response of hybrid grouper were investigated. The results showed that SSa could significantly improve the survival rate of hepatocytes, reduce the accumulation of intracellular lipid droplets, enhance the contents of mitochondrial respiratory chain I-IV and ATP to varying degrees, and inhibit mitochondrial swelling. It also significantly inhibited the up-regulation of adipogenic genes (G6PD, ME1 and DGAT2) and down-regulation of adipogenic genes (ATGL, ACO1 and LXRα). Statistical results showed that the group with 200ng/ml SSa had better protective effect. In conclusion, SSa has a protective effect on grouper hepatocyte steatosis, which can provide first-hand data and new ideas for the study of fish abnormal lipid metabolism mechanisms and the research and development of liver-protecting drugs.