General Information

Modeling methodology

The DIO (Diet-induced Obesity) mouse is a C57BL/6 mouse model of obesity constructed by feeding a high-calorie diet.The C57BL/6 is the most widely used inbred strain and the first to have its genome sequenced.The C57BL/6 mouse is susceptible to diet-induced obesity, type 2 diabetes, and atherosclerosis. Therefore, C57BL/6 mice are often used as a model for food-induced obesity.

Commonly used diets: regular maintenance diet, 60% high fat diet (60%kcal HFD) for 8-10 weeks.

Phenotype

1. Weight and insulin resistance^[1]

Fig. 1. Apparent and blood indices in DIO diet-induced induced B6 mice

Animal: C57BL/6N or C57BL/6J

Feed: Normal maintenance diet (NCD, 10% calories as fat), 60% high fat diet (HFD, 60% calories as fat)

METHODS: 3-week-old male mice were randomly grouped, the model group was induced with high-fat diet, and the control group was fed with normal chow, and the two groups of mice were fed continuously for 13 weeks.

A: Representative appearance of mice fed normal maintenance diet and high-fat diet

B: body weight change curve

C: oGTT, performed after 12 weeks of HFD treatment, mice were fasted for 16 hours and baseline blood glucose readings were obtained

D: ITT, performed after 13 weeks of HFD treatment, mice fasted for 6 hours, baseline blood glucose readings obtained

The results showed that mice given 13 weeks of high-fat dietary intervention successfully established a high-fat diet-induced obese mouse model. After 13 weeks of high-fat feeding, mice fed a high-fat diet gained significant body weight compared to mice fed a normal diet; and were glucose intolerant. Insulin tolerance test showed that the high-fat-fed mice also developed insulin resistance.

Examples of DIO mouse studies

1. Preclinical weight loss drug screening

Fig 2. weight loss effect of Celastrol in DIO mice

silico drug-screening methodsSilico drug-screening revealed that Celastrol pentacyclic triterpene extracted from the roots of Lei Shen Vine (Thunder God Vine) is a potent anti-obesity agent.Celastrol inhibits food intake, reduces energy expenditure, and leads to up to 45% body weight loss in diet-induced obesity (DIO) mice but is ineffective in leptin-deficient ( ob/ob) and leptin receptor-deficient (db/db) mouse models were ineffective. These results suggest that Celastrol is a leptin sensitizer and a promising drug for obesity. This study shows that DIO mice are effective models for preclinical anti-obesity drug screening.

DIO Mice Applications

1. modeling pre-diabetic symptoms and studying the progression of the metabolic syndrome

2. Evaluate the role of anti-obesity compounds and related conditions

3. Glucose Tolerance Test (GTT), Insulin Tolerance Test (ITT) is widely used to analyze the efficacy of compounds.

4. Modeling non-alcoholic fatty liver disease

References

1. Yu J, et al. MiR-27b-3p Inhibition Enhances Browning of Epididymal Fat in High-Fat Diet Induced Obese Mice. Front Endocrinol (Lausanne). 2019, 10:38.