A Novel Sialoglycopeptide from Gadus morhua Eggs Prevents Liver Fibrosis Induced by CCl4 via Downregulating FXR/FGF15 and TLR4/TGF-β/Smad Pathways

Liver fibrosis plays a critical role in liver disease progression. A sialoglycopeptide from the Gadus morhua eggs (Gm-SGPP) was identified having a 7000 Da molecular weight with a core pentasaccharide structure and osteogenesis activity. However, whether Gm-SGPP is beneficial to liver fibrosis remains unknown. In this study, mice with liver fibrosis were intraperitoneally injected with 2.5% CCl4 (10 mL/kg) and orally administered with Gm-SGPP (500 mg/kg) for 30 days. Results showed that Gm-SGPP alleviated oxidative liver damage and lipid metabolism disorder and reduced hepatocyte necrosis and lipid droplet accumulation. Notably, we found that Gm-SGPP increased the number and changed the composition of bile acids via increasing cholesterol 7a-hydroxylase (CYP7A1) and sterol 27-hydroxylase (CYP27A1) expression, which caused inhibition of ileum farnesoid X receptor (FXR) expression and accelerated the cholesterol conversion. Cholesterol accumulation is a risk factor for liver fibrosis. Masson staining showed that Gm-SGPP significantly reduced the degree of collagen deposition. Western blotting further suggested that Gm-SGPP downregulated the key gene of the toll-like receptor 4 (TLR4)-mediated transforming growth factor-β (TGF-β)/Smad pathway. To our best knowledge, this is the first report that Gm-SGPP prevented liver fibrosis via attenuating cholesterol accumulation. Our present results provide new ideas for the Gadus morhua egg's high-value utilization.