AIM: To improve the success rate of experimental modeling of non-alcoholic fatty liver (NAFLD) in rats by high-fat diet through comparing three different formulations of high-fat diets in constructing non-alcoholic fatty liver rats model, so as to provide a reliable animal model for the study of non-alcoholic fatty liver disease. METHODS: SPF-grade male SD rats were divided into four groups randomly: control group, high-fat diet group1 (HFD1), high-fat diet group2 (HFD2), high-fat diet group3 (HFD3). Each group was given the corresponding feed for 8 weeks while modeling. The data on general observation, body weight changes, and ingestion of the rats were recorded during the modeling period. After 8 weeks' feeding, liver ultrasound, CT and MRI examination were performed for the rats of each group to check the status. Blood and liver samples were collected. Changes in liver function (ALT, AST), blood lipids (TC, TG, HDL-C, LDL-C), and inflammatory indexes (IL-1β, IL-6, TNF-α) were detected. The morphology of the livers was observed with the naked eyes, and the liver index and Lee's index were calculated at the end of 8 weeks. The effects of different high-fat diets on the establishment of NAFLD model in SD rats were comprehensively evaluated by comparing the difference of above indexes among the groups. RESULTS: Compared with the control group,rats in the HFD1, HFD2 and HFD3 groups showed poor mental deterioration, decreased activity, severe hair loss, decreased food intake, increased body weights, and significantly increased liver index and Lee's index, along with increased liver volume, blunt edge, steatosis and lipid deposition, and the trend was even more pronounced in the HFD3 group. Compared with the control group, the serum levels of ALT, AST, TC, TG, LDL-C, IL-1β, IL-6 and TNF-α were significantly increased, while the contents of HDL-C was significantly decreased in the HFD1, HFD2 and HFD3 group,especially in the HFD3 group. Compared with the control group, the B ultrasonography showed an enlarged liver with enhanced parenchymal echo and pipe unsharpness, CT showed that the liver and spleen CT ratio decreased obviously,and the MRI images showed obvious difference of liver signal intensity between in/out of phase image in the HFD1, HFD2 and HFD3 group, and the most significant imaging changes was observed in the HFD3 group. CONCLUSION: The above three kinds of high-fat diets can establish NAFLD model in SD rats after 8 weeks' feeding, the models induced by HFD3 was better than those induced by the other two groups. NAFLD lesion is relatively serious and expected to last longer in HFD3 group, which are more suitable for investigating the underlying mechanisms of non-alcoholic fatty liver disease and development of lipid-lowering drugs.
