Effects Of Treatment With Sitagliptin On Serum And Different Tissues Retinol Binding Protein 4 Expression Levels In High-fat-fed Obesity Rats

Background The level of serum retinol binding protein 4(RBP4) in patients with impaired glucose regulation or diabetic patients was significantly higher than the healthy control group. RBP4 as a new adipokine, has the effect of causing insulin resistance(IR), and participate in a series of IR-related diseases, including diabetes, metabolic syndrome, nonalcoholic fatty liver disease progression. Sitagliptin as dipeptidyl peptidase-4(DPP-4) inhibitor, having a stimulating pancreatic β cell regeneration, promoting insulin secretion, inhibition of endogenous glucose production, to reduce blood sugar.Objective To evaluate the effects of treatment with sitagliptin on metabolic parameters, serum RBP4 levels, epididymal adipose tissue and liver RBP4 expression levels in high-fat-fed obese rats.Methods 40 Sprague-Dawley(SD) rats were randomly divided into normal diet group(ND group, n=10), fed with normal chow, high fat diet group(HD group, n=30), fed with high fat diet. 16 weeks later, obese models(n=16) were established from HD group and were randomly divided into obesity group(OB group, n=8) and sitagliptin group(SITA group, n=8). Measure Body weight(BW), fasting blood glucose(FBG), triglyceride(TG), total cholesterol(TCH), high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), fasting insulin(FINS), serum RBP4 respectively before and after the 6 weeks of treatment, and calculate HOMA-IR.Western blotting was used to detect the epididymal adipose tissue and liver RBP4 protein expression levels after all the rats were killed.Result ① The levels of BW, FBG, TG, TCH, LDL-C, FINS, HOMA-IR and serum RBP4 in HD group increased while the levels of HDL-C decreased compared with those of ND group with a statistical significance(P<0.05). The differences between OB group and SITA group were of no statistical significance. After treatment with sitagliptin, the levels of FBG, TG, TCH, LDL-C, FINS, HOMA-IR and serum RBP4 of SITA group decreased while the levels of HDL-C increased compared with those of OB group with a statistical significance(P<0.05). ② Epididymal adipose tissue RBP4 protein expression levels in OB group increased compared with ND group(P<0.05), epididymal adipose tissue RBP4 protein expression levels in SITA group decreased compared with OB group(P<0.05). ③ Pearson correlation analysis showed that in ND group, serum RBP4 was positively correlated with TG, in HD group, serum RBP4 and FINS, HOMA-IR, TG,epididymal adipose tissue RBP4 were positively correlated and negative correlation existed between serum RBP4 and HDL-C.Conclusion 1. Serum and epididymal adipose tissue RBP4 protein levels are elevated in obesity rats. 2. Sitagliptin intervention can lower serum and epididymal adipose tissue RBP4 protein levels in obesity rats and improve the glucose and lipid metabolism.