Background and aim: The increase in NASH prevalence coincides with the current obesity pandemic. Obesity is characterized by a state of chronic inflammation with oxidative stress in adipose tissue and liver. A high fat/sugar diet can induce non-alcoholic steatohepatitis, which is characterized by inflammation, hepatocyte swelling, and steatosis. To assess molecular, histological, and biochemical changes in a murine NASH model subjected to a high-fat diet for 16 weeks.
Material and methods: Male mice 4-5 weeks old, C57BL / 6J were fed a high-fat diet (HF, 60% fat, 42gr / L sugars in water) for 16 weeks. Every 4 weeks 4 mice were sacrificed for a follow-up of the model at 4, 8, 12 and 16 weeks. Serum glucose was measured after 4hours of fasting, animal weight and caloric intake. The liver was removed and weighed, as was the epididymal adipose tissue. AST, ALT, TAG, Chol and VLDL were measured. Immunohistochemistry was performed for α-SMA and hematoxylin-eosin staining, Masson's trichrome and Syrian red. The hepatic expression of IL-6, TNFα, COL1A1 and TGF-β mRNAs was determined by qRT-PCR. Quantitative variables were analyzed with ANOVA, Tukey for parametric data and Kruskal-Wallis for non-parametric data. Opinion CI00518 of ethics and investigation committee.
Results: Animals at week 16 showed high body weight compared to animals with standard diet, presence of steatosis and liver inflammation (p<0.05). Serum glucose increased at week 12 and 16 (p<0.05). The weight of the liver and epididymal fat increases as the model is established, without achieving statistical significance. The histological parameters coincide with the establishment of a steatohepatitis, while the values of the biochemical parameters increase remarkably compared to the control group. Inflammatory and fibrotic genes increase at 16 weeks compared to the control group.
Conclusions: Exposure to a diet high in fat and simple sugars induced increased body weight, steatohepatitis, inflammation, hyperglycemia, and increased expression of liver enzymes and genes involved in inflammation and fibrosis.
Conflicts of interest: The authors have no conflicts of interest to declare.
