With the change of people's diet structure in modern society, the intake of high-calorie food, especially animal fat, continues to increase, resulting in more and more obesity. Obese people not only suffer from cosmetic problems, but also have a higher risk of type 2 diabetes, fatty liver disease, high blood pressure, heart disease, stroke, gallbladder and pancreatic cancer. Both the study of the mechanism of fat loss and the testing of weight loss drugs are inseparable from appropriate animal models. In rat and mouse models, there is a positive association between dietary fat intake and obesity, and they are considered suitable models to study dietary obesity.

We have developed a series of obese mouse models, including diet-induced obesity models and spontaneous obesity models caused by genetic mutations. At the same time, we are equipped with a series of sampling and testing equipment to provide one-stop pharmacodynamic evaluation services. Several examples of common DIO models for obesity are listed below.

（1）60% HFD diet-induced obesity (DIO) model

1. Experimental scheme: according to the needs of the experiment, C57BL/6J, C57BL/6N, or SD rats can be selected.

2. Experimental data

Figure 1. C57BL/6 mice were fed high-fat diet (60% kcal fat, D12492) for 8-12 weeks to induce obesity (n=10). After 10 weeks of feeding a high-fat diet compared to a normal diet, a significant increase in fasting blood glucose was seen (fasting for 14 to 16 hours).

The results showed that C57BL/6 mice were fed D12492 at the age of 6 weeks. After 8 weeks of feeding, the weight of C57BL/6 mice was significantly different from that of the control group, and metabolic syndrome, neuropathy, insulin resistance, and elevated blood sugar occurred at 10~12 weeks. In rat and mouse models, there was a positive association between dietary fat intake and obesity, and the severity of HFD-induced NAFLD was associated with the following factors: (1) species, rats are more sensitive than mice, and rats develop severe histological NAFLD manifestations in a shorter time; (2) Strain SD was more sensitive than Wistar rats; C57BL/6 is more sensitive than BALB/c and C3H/HeN. (3) Sex, male mice are more sensitive than female mice, which is generally believed to be related to the protective effect of estrogen.

（2）Mc4r KO+HFD diet-induced obesity (DIO) model

1. Experimental scheme: when Mc4r KO mice were fed HFD diet for 8 weeks, the weight of Mc4r KO mice reached 30 g from 6 to 8 weeks of age, showing obvious obesity. They were fed high-fat diet and weighed continuously for 34 to 50 weeks, once a week.

2. Experimental data

Figure 2. Weight change curve of Mc4r KO mice fed HFD diet

The results showed that after 8 weeks of HFD feeding, Mc4r KO mice began to show liver steatosis, lobular inflammation and hepatocellular balloonlike degeneration at 10 to 12 weeks, liver fibrosis at 20 to 24 weeks, and hepatocellular carcinoma at 11 months, which was similar to the model characterized by human MASH model. The Mc4r KO mice provide a new mouse model of NAFLD and MASH to study the sequence that constitutes diet-induced hepatic steatosis, liver fibrosis, and HCC, and to help understand the pathogenesis of MASH, search for specific biomarkers, and also enable preclinical evaluation of new drugs.

（3）B6-Alms1 KO Obesity (DIO) model

1. Experimental scheme:similar to Mc4r KO mice, Alms1 KO mice were born obese and fed a WD diet (AIN-76A, HF-HC) for 4 to 24 weeks.

2. Experimental data：

Steatosis was present at 4 weeks, glucose tolerance, dyslipidemia, and MASH were present at 4-8 weeks, accompanied by cardiovascular and kidney disease, specific changes in microbial dysregulation, and increased intestinal permeability prior to fibrosis, MASH and grade 3 fibrosis were present at 12 weeks, and HCC was present in 75% of mice at 24 weeks. This model faithfully generalizes the human MASH condition characterized by a combination of genetic, environmental, and nutritional factors.