Effects of dextran sulfate sodium- induced colitis on non-alcoholic steatohepatitis in mice

Abstract

Gut-liver interaction has many implications for development and progression of diseases. Disruption of intestinal barrier function is one of the exacerbation factors of liver disease. The effect of colitis was investigated on non-alcoholic steatohepatitis (NASH) in dextran sulfate sodium (DSS)-induced colitis model mice. In this study, 6-week-old male C57BL/6j mice were divided into 4 groups. DSS+CDAA group was provided 1.25% DSS water and choline-deficient, methionine-lowered, amino acid-defined diet (CDAA diet), CDAA group was given tap water and CDAA diet, DSS group was fed DSS water and normal diet, and Control group was provided water and standard diet. At necropsy, large intestine and liver were collected for gene expression and histopathological analysis. In DSS group, large intestine was induced colitis. In addition, inflammation-related gene expression was increased in the liver, suggested the effects due to colitis. In CDAA group, the NASH lesions were confirmed in the liver. In DSS+CDAA group, the expression of inflammation-related genes including TLR4 and CXCL16-positive cells were increased in the liver. Furthermore, TGF beta and alpha-SMA gene expression were thought to be upregulate by M2 polarization of hepatic macrophage, suggested disruption of intestinal barrier function may exacerbated hepatic fibrosis. DSS-induced colitis was caused disruption of intestinal barrier mechanism and increased the influx of LPS into liver, as a result, it was considered to exacerbate of NASH lesions induced by the CDAA diet.