Impact of multiple different high-fat diets on metabolism, inflammatory markers, dysbiosis, and liver histology: study on NASH rat model induced diet

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 documented for body weight. Blood samples were taken for biochemical analysis: 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). Feces were taken for short-chain fatty acid (SCFA) analysis. Liver histology was analyzed using NAS (NAFLD activity score). The comparison test was carried out using the one-way ANOVA or Kruskal–Wallis test. Results: The highest average body weight was in the WD group (346.14 g). Liver enzymes, LDL, triglyceride, propionic acid, and acetic acid in each group were not significantly different. TNF-α, IL-6, and hepatic lipase were significant (p = 0.000; p = 0.000; p = 0.004) and the highest was in the HFD group. Butyrate level was significant (p = 0.021) and the least was in the HFHFD group (4.77 mMol/g). Only WD and HFHFD had an NAS ≥ 5 (14% and 14%). The highest percentage of borderline NAS was found in WD (57%). Conclusions: The HFD group showed significant liver inflammation but did not produce NASH histologically, whereas the WD and HFHFD groups had the potential to develop NASH because the diets affected metabolic and inflammatory parameters as well as liver histology.