ObjectiveTo establish a rat model of diet-induced obesity (DIO), and explore its molecular mechanism. MethodsNinty 3-week old male Sprague-Dawley rats in the diet-induced obesity (DIO) experimental group were fed with high fat diet (containing 30% fat) for 25 weeks, and 20 healthy rats in the normal control group were fed with normal diet. The following indicators were evaluated:body weight, Lee''s index, the fasting glucose and insulin levels and pathological changes in the liver tissue. The expression of acetyl-CoA carboxylase (ACC), fatty acid synthetase (FAS), hormone-sensitive lipase (HSL), which are key enzymes in lipid metabolism, and the transcription factor sterol regulatory element binding protein-1c (SREBP-1c) was analyzed by real-time PCR. ResultsDIO rat models were successfully produced by high fat diet for 25 weeks. Compared with the normal rats, after fed with high fat diet for 6 weeks, the DIO rats showed significant increase in the body weight and Lee''s index. After high fat diet for 25 weeks, the DIO rats showed abnormal liver fat accumulation and moderate to severe fatty liver, significant increase in the fasting glucose and insulin levels, and insulin resistance. Real-time PCR results revealed that compared with the normal rats, after feeding with high fat diet for 25 weeks, the expression of ACC, FAS, HSL and the transcription factor SREBP-1c were increased significantly in the liver of DIO rats. The expression of SREBP-1c in the liver of DIO rats was 2.56-fold higher than that of the normal rats. ConclusionsWe have successfully induced normal SD rats to develop diet-induced obesity by feeding high fat diet for 25 weeks. The expressions of lipid metabolism genes SREBP-1c, ACC, FAS and HSL are all involved in the development of DIO, providing an explaination to the relationship between the changes in hepatic lipid metabolism and the development of obesity.