Abstract
BACKGROUND: The spectrum of non-alcoholic fatty liver disease (NAFLD), known as non-alcoholic steatohepatitis (NASH), can lead to advanced liver disease. It is known that a variety of diets play a significant role in the development of NAFLD/NASH. The goal of this study was to determine the most appropriate composition of diet to induce NASH in an animal model. METHODS: This research used Rattus norvegicus strain Wistar (n=27), which were divided into four groups and given each diet for 12 weeks: normal diet (ND, n=7), high-fat diet (HFD, n=6), western diet (WD, n=7), and high-fat-high-fructose diet (HFHFD, n=7). Subjects were monitored for changes in body weight. Blood samples were collected for biochemical analysis, including low-density lipoprotein (LDL), triglyceride, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), hepatic lipase, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and lipopolysaccharide (LPS). Fecal samples were taken for short-chain fatty acid (SCFA) analysis. Liver histology was assessed using NAS (NAFLD activity score). A statistical comparison test was carried out using the one-way ANOVA or Kruskal-Wallis test. RESULTS: The highest average body weight was observed in the WD group (346.14 g). Liver enzymes, LDL, triglyceride, propionic acid, and acetic acid did not show significantly differences among the groups. TNF-α, IL-6, and hepatic lipase were significant (p = 0.000; p = 0.000; p = 0.004) and the highest level recorded in the HFD group. Butyrate acid level also showed significances (p = 0.021) with the lowest concentration seen in the HFHFD group (4.77 mMol/g). Only WD and HFHFD had a NAS ≥ 5 (14% and 14%). The highest percentage of borderline NAS was found in WD (57%). CONCLUSIONS: WD feeding is the most appropriate diet type to induce NASH in rats as it influences metabolic, inflammatory, dysbiosis, and liver histology of rats.