Glycosaminoglycan from Ostrea rivularis attenuates hyperlipidemia and regulates gut microbiota in high‐cholesterol diet‐fed zebrafish

Hyperlipidemia an immense group of acquired or genetic metabolic disorders that is characterized by an excess of lipids in the bloodstream. Altogether, they have a high prevalence worldwide and constitute a major threat to human health. Glycosaminoglycans (GAG) are natural biomolecules that have hypolipidemic activity. The purpose of this study was to investigate the potential hypolipidemic effect of glycosaminoglycans extracted from Ostrea rivularis (OGAG) on hyperlipidemic zebrafish, as well as the possible underlying mechanism of such effect. Dietary supplementation with OGAG during 4 weeks significantly reduced the serum and hepatic lipid levels and the hepatosomatic index in hyperlipidemic zebrafish. In addition, histopathological showed that OGAG supplementation decreases the volume and number of lipid droplets in hepatocytes. Transcriptome and real‐time quantitative polymerase chain reaction analysis revealed that the gene expression levels of PPARγ, SCD, HMGRA, ACAT2, HMGCS, and HMGCR were significantly downregulated by OGAG treatment in hepatocytes, whereas those of CD36, FABP2, FABP6, ABCG5, and CYP7A1 were significantly upregulated. This suggests that the hypolipidemic effect of OGAG relies on increasing the ketogenic metabolism of fatty acids, inhibiting cholesterol synthesis, and enhancing the transformation of cholesterol to bile acid. Furthermore, OGAG treatment improved gut microbiota imbalance by reducing the Firmicutes‐to‐Bacteroidetes ratio, increasing the relative abundance of beneficial bacteria (Bacteroidetes, Verrucomicrobia, Acidobacteria, and Sphingomonas), and reducing the relative abundance of harmful bacteria (Proteobacteria, Cohaesibacter, Vibrio, and Terrisporobacter). These findings highlight the potential benefit of implementing OGAG as a dietary supplement to prevent and treat hyperlipidemia.