High-fat diet combined with dextran sulfate sodium failed to induce a more serious NASH phenotype than high-fat diet alone

Abstract

Background and Aims: Animal models are essential tools to investigate the pathogenesis of diseases. Disruption in the intestinal epithelial barrier and gut vascular barrier is an early event in the development of non-alcoholic fatty liver disease (NAFLD). Intestinal epithelial barrier can be destroyed by dextran sulfate sodium (DSS) oral administration. High fat diet (HFD)-induced non-alcoholic steatohepatitis (NASH) rat model has been widely used. Recently, the combination of HFD with DSS induced NASH model has also been reported. The present study aimed to evaluate whether this composite NASH animal model is more ideal than that induced by HFD alone.Methods: Rats were divided into control, HFD and HFD combined with DSS (DSS + HFD) groups. They were fed with routine diet, high-fat diet, and HFD combined with DSS drinking, respectively, for 22 weeks. Histopathological analysis (HE staining, Oil-Red O staining, Masson staining), lipid parameters testing (TG, TC, GLU, NEFA, TRIG, LDL, HDL), testing on indicators of inflammation (TNF-α, ALT, AST, ALP, LDH) and oxidative stress (MDA, SOD, CAT) were performed.Results: Rats in HFD and DSS + HFD group displayed increase in the body weight, liver weight, lipids accumulation and the levels of TNF-α, ALT, AST, ALP, MDA in serum and liver accompanied with impaired glucose tolerance, obvious hepatitis, and decreased levels of SOD and CAT in serum and liver compared to those in control group. Moreover, in the DSS + HFD group, but not in the HFD group, proliferation of fibrous tissue in the portal area and the hepatic lobules was found.Conclusion: The addition of DSS on high-fat diet did not exacerbate lipid accumulation and inflammation, but induced NASH-related liver fibrosis.

Vitamin D improves hepatic steatosis in NAFLD via regulation of fatty acid uptake and β-oxidation

“…HFD is a well-established modeling method, which can lead to the development of metabolic syndrome, hepatic steatosis, and NASH in experimental animals (78). The duration of dietary intake and VD treatment in previous studies ranges from 10 weeks to 22 weeks and 3 weeks to 10 weeks, respectively, thus impacting the severity of NAFLD and effect of treatment (56,(79)(80)(81). In the present study, rats were fed with an HFD for 14 weeks, and the NAFLD model was determined by sacrifice at Week 7.…”

Molecular Mechanisms and Mediators of Hepatotoxicity Resulting from an Excess of Lipids and Non-Alcoholic Fatty Liver Disease

“…A reduction in the expression of TLR4 in mutating mice has been shown to be protective against the development of NASH [37]. Mice that received high-fat diet and dextran sulfate sodium (DSS) had high levels of bacterial lipopolysaccharides in the portal circulation, a higher expression of TLR4, and severe liver inflammation when compared with the controls [38]. TLR4 may be the key component of the gut microbiota−liver axis, which influences the development of NASH [39].…”