Effect of Emodin on Hyperlipidemia and Hepatic Lipid Metabolism in Zebrafish Larvae Fed a High‐Cholesterol Diet**

Abstract Hyperlipidemia (HLP) is a complex pathological condition results from lipid metabolism disorder, which is closely related to obesity, atherosclerosis and steatohepatitis. Emodin (EM), a natural anthraquinone, exhibits prominent hypolipidemic effects. However, its exact mechanism is still unclear. In this study, we successfully established hyperlipidemic zebrafish model induced by 4 % high‐cholesterol diet (HCD) for 10 days and explored the anti‐hyperlipidemic roles and underlying mechanisms of EM. The results indicated that EM attenuated the mortality and body mass index (BMI) of zebrafish with HLP, and ameliorated abnormal lipid levels involved in TC, TG, LDL−C and HDL−C levels. Besides, EM effectively reduced lipid accumulation in blood vessels and liver, alleviated hepatic histological damage, and inhibited vascular neutrophil inflammation. Finally, the mRNA expression of molecules related to lipid metabolism were studied by using real‐time quantitative polymerase chain reaction (RT‐qPCR) to investigated the underlying mechanism. Further results found that treatment with EM up‐regulated AMPKα, LDLR, ABCA1 and ABCG1, and down‐regulated SREBP‐2, PCSK9 and HMGCR expression. In conclusion, EM showed a prominent mitigative effect on lipid metabolism disorder in zebrafish larvae with HCD‐stimulated HLP, which was associated with the enhancement of LDL−C uptake and reverse cholesterol transport, and inhibition of cholesterol synthesis.