Abstract:Objective: To explore the effect of obesity induced by high fat diet on liver glycometabolism, and to reveal the molecular mechanism of pomegranate peel extract (EPP) in improving the disorder of glycometabolism and lipid metabolism in obese rats. Methods: Rats were fed with high-fat diet (D12451) and control diet (D12450H) for 16 weeks to replicate the obese animal model. Three doses of EPP (50, 100, 200 mg/kg) were administered by intragastric administration simultaneously with the model. Result: After 16 weeks of feeding with high fat diet, the body weight, Lee's index and liver weight index of rats increased, the levels of serum TC, TG, LDL-C and FFA increased, and the levels of HDL-C decreased. High dose of EPP could significantly improve the body weight, Lee’s index, liver weight index and blood lipid level of rats with high fat diet. It showed that EPP could effectively reduce the obesity induced by high-fat diet. At the same time, the results showed that EPP significantly reduced the liver microstructure and liver function damage of fat rats induced by fat. The detection of insulin resistance and hepatic glucose metabolism in rats showed that there was significant blood glucose increase and insulin resistance in rats with high-fat diet. High-dose EPP could significantly reduce blood glucose and improve insulin resistance. And EPP could increase liver tissue IRS-2 and GLUT2 protein levels. Conclusion: EPP exerted liver protection by reducing blood lipids in obese rats and improving hepatic glucose metabolism disorders.