The effects of sitagliptin on nonalcoholic fatty liver disease in diet-induced obese rats

Aim: To determine the effects of sitagliptin on NAFLD in rats with diet-induced obesity.Materials and Methods: 24 weeks aged, 199-240 grams, twenty four adult-female Sprague-Dawley rats were used. The rats were randomly separated into 2 groups. The control group (n:6) was fed with standard rat diet. The other group (n:18) was fed with a high fat diet (HFD) to induce NAFLD. After 12 weeks, rats which were fed with a HFD were randomly seperated into 2 groups. NAFLD group was fed with a HFD for an additional 4 weeks. Sitagliptin group received sitagliptin (3 mg/kg) for 4 weeks in addition to HFD. Changes in weight were recorded throughout the study. At the end of the study blood samples were drawn from all rats to determine the levels of serum glucose, triglyceride, cholesterol, AST, ALT, DHEA-S and plasma insulin. Insulin resistance was determined using the HOMA-IR index. Histopathologic evaluation of liver samples were undertaken.Results: Serum glucose (p<0.001) and insulin (p<0.001) values were significantly lower in the sitagliptin group compared to NAFLD group. HOMA-IR index was significantly lower (p<0.001) in the sitagliptin group compared to NAFLD group. The sitagliptin group had lower serum levels of triglycerides (p<0.001) and cholesterol (p<0.001) than NAFLD group. Hepatic steatosis was significantly less (p<0.001) in the sitagliptin group compared to NAFLD group while no difference was seen in hepatic inflammation (p=0.057). The sitagliptin group had no difference in hepatomegaly and liver transaminase levels compared to NAFLD group. No significant association was determined between DHEA-S and hepatic steatosis (r=0.009, p=0.967).Conclusion: Sitagliptin appears to improve hepatic steatosis by increasing insulin sensitivity and regulating lipid profiles in rats.Keywords: Sitagliptin, hepatic steatosis, metabolic syndrome