The obesity and nonalcoholic fatty liver disease mouse model revisited: Liver oxidative stress, hepatocyte apoptosis, and proliferation.

The study revisited the diet-induced obesity (DIO) mice and the nonalcoholic fatty liver disease (NAFLD) pathogenesis to serve as a translational model. Hepatic beta-oxidation pathways, lipogenesis, oxidative stress, hepatocyte apoptosis, and proliferation were investigated in obese mice. Three-month-old male mice were divided according to their diet for fifteen weeks, the control diet (C group, containing 10% energy from fat) and the high-fat diet (HF group, containing 50% energy from fat). Body weight (BW), liver mass, and steatosis were higher in the HF group than in the C group. Also, gene expression related to beta-oxidation and lipogenesis showed an adverse profile, and insulin and glucose signaling pathways were impaired in the HF group compared to the C group. As a result, steatosis was prevalent in the HF group but not in the C group. Furthermore, the pathways that generate NAFLD were negatively modulated by oxidative stress in the HF animals than in the C ones. The caspase 3 immunolabeled HF hepatocytes with increased gene and protein expressions related to apoptosis while proliferating cell nuclear antigen labeled C hepatocytes. In conclusion, the findings in the DIO mouse model reproduce the NAFLD profile relative to the human NAFLD's apoptosis, insulin signaling, lipogenesis, beta-oxidation, and oxidative stress. Therefore, the model is adequate for a translational perspective's morphological, biochemical, and molecular research on NAFLD.