A short-term rodent model for non-alcoholic steatohepatitis induced by a high-fat diet and carbon tetrachloride

Several models of mice-fed high -fat diets have been used to trigger non-alcoholic steatohepatitis and some chemical substances, such as carbon tetrachloride. The present study aimed to evaluate the joint action of a high -fat diet and CCl 4 in developing a short-term non-alcoholic steatohepatitis model. C57BL6/J mice were divided into two groups: standard diet-fed (SD), the high -fat diet-fed (HFD) and HFD + fructose-fed and carbon tetrachloride (HFD+CCl 4 ). The animals fed with HFD+CCl 4 presented increased lipid deposition compared with both SD and HFD mice. Plasma cholesterol was increased in animals from the HFD+CCl 4 group compared with the SD and HFD groups, without significant differences between the SD and HFD groups. Plasma triglycerides showed no significant difference between the groups. The HFD+CCl 4 animals had increased collagen deposition in the liver compared with both SD and HFD groups. Hydroxyproline was also increased in the HFD+CCl 4 group. Liver enzymes, alanine aminotransferase and aspartate aminotransferase, were increased in the HFD+CCl 4 group, compared with SD and HFD groups. Also, CCl 4 was able to trigger an inflammatory process in the liver of HFD-fed animals by promoting an increase of -2 times in macrophage activity, -6 times in F4/80 gene expression, and pro-inflammatory cytokines (IL -1b and TNFa), in addition to an increase in inflammatory pathway protein phosphorylation (IKKbp). HFD e HFD+CCl 4 animals increased glucose intolerance compared with SD mice, associated with reduced insulin-stimulated AKT activity in the liver. Therefore, our study has shown that short-term HFD feeding associated with fructose and CCl 4 can trigger non-alcoholic steatohepatitis and cause damage to glucose metabolism.