Beneficial effect of sitagliptin on high fat diet induced obesity in wistar rats

Abstract

Purpose Obesity is one of the rising health problems and has become a major concern with highest prevalent global epidemiology. Various evidences suggest that the action or effect of glucagon-like-peptide-1 (GLP-1), which acts as a satiety signal may be impaired in obese subjects. Dipeptidyl peptidase-4 (DPP-4) is the principal enzyme that metabolizes GLP-1 and sitagliptin, a DPP-4 inhibitor which prevents the breakdown of GLP-1. Thus the purpose of the present study was to investigate the beneficial effect of sitagliptin, a DPP-4 inhibitor on body weight gain, adiposity and biochemical anomalies in rats. Materials and methods In the present study chronic administration of sitagliptin (10, 20 and 40 mcg/kg/day p.o) for 6 weeks along with high fat diet to the obese rats which were pretreated with high fat diet feeding for 4 weeks on the various parameters of obesity were analyzed. Their effects on body weight, feed intake (kcal), weight and size of fat pads, levels of serum glucose, triglycerides, total cholesterol, high density lipoproteins (HDL) and low density lipoprotein were analyzed. Results Treatment with sitagliptin (10, 20 and 40 mcg/kg/day p.o) produced significant dose dependent decrease (p < 0.05) in body weight gain, feed intake (kcal), weight and size of fat pads, levels of serum glucose, triglycerides, total cholesterol and low density lipoproteins as compared to high fat diet group. Moreover level of serum high density lipoproteins were increased as compared to high fat diet group. Sitagliptin, a DPP-4 inhibitor positively modulates the parameters of obesity and the effect was comparable to orlistat, a well reported drug for obesity.