Rutin ameliorates HCD-induced cholesterol metabolism disorder in zebrafish larvae revealed by transcriptome and metabolome analysis

Changes in modern lifestyles have led to an increase in obesity rates. Excessive lipid accumulation leads to abnormal cholesterol metabolism, and maintaining a balanced cholesterol metabolism is essential for the normal functioning of cells and the body. Rutin belongs to the group of flavonoids with hypolipidemic, anti-inflammatory and antioxidant effects. The aim of this study was to investigate the role of rutin in cholesterol metabolism disorders induced by a high cholesterol diet in zebrafish larvae. The trial was divided into five groups: Normal diet (ND), 5 % high cholesterol diet (HCD), 5 % high cholesterol diet with 80 μg/g ezetimibe diet (EZE), 5 % high cholesterol diet with 5 % rutin diet (RL-HCD), and 5 % high cholesterol diet with 10 % rutin diet (RH-HCD). Zebrafish larvae at 5 dpf were randomly divided into five groups and continuously fed different diets for 10 days, after 10 days zebrafish samples were collected for subsequent experiments. Body length, body width, oil red O, and Nile red staining were measured to detect biochemical indexes, analyze inflammatory response and lipid accumulation. Vascular endothelial injury was assessed by stereofluorescence microscopy and ELISA. In order to study the protective effect of rutin in zebrafish with cholesterol metabolism disorder induced by HCD, RNA-seq and LC-MS/MS nontargeted metabolomics were employed. The results indicate that HCD led to an increase in the body length and width of zebrafish. The HCD group induced an increase in body length and width, lipid accumulation, and exacerbated inflammation. Additionally, vascular damage and abnormal expression of endothelial cell markers were observed. Rutin lowered lipid levels in zebrafish fed an HCD, reduced inflammation, and protected endothelial cells. The RNA-seq and metabolomic analysis combined demonstrated that rutin effectively ameliorates the disorder of cholesterol metabolism in vivo by reducing cholesterol synthesis and promoting cholesterol transport.