Impact of Various Diets and Induction Methods on Lipid Metabolism and Liver Histopathology in NASH Model C57BL/6J Mice

Introduction The development of the Non-Alcoholic Steatohepatitis (NASH) model in mice is a challenging endeavor as it requires a very natural method that closely mimics the condition observed in people. Multiple techniques are employed to generate NASH; however, they frequently yield diverse and uncertain results. One strategy that has been adopted to give a second hit and hasten the development of NASH is the administration of CCl4. Unfortunately, its efficacy and comparison to other diets, such as CDAHFD, have yet to be determined. Aim The study aims to investigate the impact of different high-fat diets and CCl4 intervention on metabolism and liver histology in C57BL/6J mice to establish a reliable and efficient NASH model. Method A true experimental study with post-test only control group design was conducted in the study. A total 24 mice C57bl/6J, aged 8-12 weeks were used in the study. Mice were divided into 4 groups: Normal diet (K), Western diet (WD) + CCl4 (0.2 µl/kgbw/week IP) for 8 weeks (P1), Western diet (WD) for eight weeks (P2), Choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) for eight weeks (P3). The diets were given 2 months, and CCI4 was given 0,2 cc/kgbw 2 times per week. After the research period, the mice were euthanized, and further analysis was conducted on the liver and blood samples. The statistical analysis was performed using One-Way ANOVA and the Kruskal-Wallis test based on the provided data. Result The WD+CCI4 group showed the lowest lipid profile in comparison to the other groups (Chol total: 49,80 ± 10,52, HDL: 21,80 ± 8,10, Trigliceryde: 87,00 ± 47,13), but it also expressed the highest ALT (902 ± 520.80, P<0,05) and AST ALT (902 ± 520.80, P<0,05) values, which implies liver inflammation. Mice that were administered the CDA-HFD exhibited the most elevated lipid profile Chol total: 152,6 ± 20,89, HDL: 96,80 ± 11,56, Trigliceryde: 216,4 ± 56,49) in comparison to other groups; however, they did not exhibit any indications of inflammation from liver function tests or histology. With over 50% of testing positive for NASH, the WD+CCI4 group exhibited the highest NAS score compared to the others (P<0,05). Conclusion In comparison to the other groups, the Western diet and CCI4 were both effective in inducing the NASH model. However, the CDA-HFD diet was more effective in inducing the NAFLD model in C57bl/6J mice