Study Of Nesfatin-1 Improves On Glucose And Lipid Metabolism In Obese Rats

Objective: Nesfatin-1 has been found to inhibit feeding independently of the leptin pathway,but its mechanism remains to be clarified.In this study,we established an obese rat model to observe the effect of Nesfatin-1 on glucose and lipid metabolism,and analyzed the changes of Nesfatin-1 and glucose and lipid metabolism-related microrna(mi RNA)expression levels,and explored the mechanism of Nesfatin-1.Methods: The obese rats were successfully established by weight measurement,Lee’s index calculation and glucose tolerance test(OGTT).The obese rats were randomly divided into four groups: Model groups,low dose Nesfatin-1 group,medium dose Nesfatin-1 group and high dose Nesfatin-1 group.Rats in each group were injected with Nesfatin-1 or normal saline by tail vein for 5 weeks,and the changes of body weight,food intake and liver weight were recorded during the experiment.The changes of fasting blood glucose(FBG),serum total cholesterol(TC),triglyceride(TG),fasting insulin(FINS)and free fatty acid(FFA)in rats were detected by ELISA,and the ability of Nesfatin-1 to regulate glucose and lipid metabolism was evaluated.Then,real-time fluorescence quantitative PCR(RT-q PCR)was used to detect the expression levels of glucolipid metabolization-related mirnas in rat liver tissues,and target genes of detected mirnas were predicted using Target Scan and mi RDB databases to analyze the mechanism of Nesfatin-1 regulating glucolipid metabolism.Results :(1)Nesfatin-1 had a certain regulation effect on body weight,food intake and liver weight of obese rats.Compared with Model groups,Nesfatin-1 had a very significant inhibition effect on body weight growth of rats(P < 0.01),and high dose Nesfatin-1 had the best effect.In the first 3h after Nesfatin-1 treatment,the food intake of rats was significantly decreased(P<0.01),but at 24 h,the inhibitory effect of low dose Nesfatin-1 was the most significant.Compared with normal control group,The liver weight of rats in saline group and Nesfatin-1 low-dose group was significantly increased(P < 0.01),and liver weight of rats in medium-high dose Nesfatin-1 group was significantly increased(P < 0.05).Compared with Model groups,liver coefficient of Nesfatin-1 medium-high dose group was significantly decreased(P < 0.05).(2)Compared with Model groups,serum FFA level in Nesfatin-1 low-dose group was significantly decreased(P <0.05),TC level in Nesfatin-1 group was extremely significantly decreased(P <0.01),and serum TG level in Nesfatin-1 medium-high dose group was extremely significantly decreased(P <0.01).(3)The detection results of mi R-122 and mi R-802 in rat liver showed that the expression levels of mi R-122 and mi R-802 in Nesfatin-1 group were significantly decreased;Comparison analysis of target gene prediction database Target Scan and mi RDB showed that GYS1 was the potential target gene of mi R-122 and TMED9 gene was the potential target gene of mi R-802.Conclusions :(1)Nesfatin-1 can inhibit appetite,decrease body weight and liver weight in obese rats.(2)Nesfatin-1 can improve glucose and lipid metabolism disorder in rats.(3)Nesfatin-1 reduces the expression levels of mi R-122 and mi R-802,and reducing the occurrence of insulin resistance and fat production.