Effects And Underlying Mechanisms Of Vaspin On Insulin Resistance Of Rats Under High-fat Diet

Objective:1.To investigate whether vaspin can improve insulin resistance of high-fat diet fed rats;2.To investigate whether vaspin can improve insulin resistance via IRS/PI3K/Akt and NF-?B signaling pathways in the liver of high-fat diet fed rats.Methods:Thirty male Sprague-Dawley rats(8-week-old)were purchased from the Laboratory Animal Center of Shanxi Medical University.After one week of adaptive feeding,the rats were randomly assigned into normal diet group(n=10)and high-fat-diet group(n=20).The high-fat-diet group was given an high-fat diet for 16 weeks to induce insulin resistance.Then the group of rats following the normal diet was keeping normal diet(NC group,n=10),the insulin resistance rats were randomly divided into two subgroups:keeping high fat diet(HFD group,n=10)and intraperitoneally administration of vaspin at doses of 320 ng/ml(HFD+vaspin group,n=10)for 8 weeks.NC group and HFD group were administered with normal saline as a control.At the end of intervention,body weight of the rats was measured and blood samples were collected for detecting of serum concentrations of FBG?FINS?TG?TC?TNF-? and IL-6.The oral glucose tolerance test(OGTT)and insulin tolerance test(ITT)were performed in overnight-fasted rats to assess the glucose tolerance and insulin resistance.The hyperinsulinemic-euglycemic clamp test was performed to evaluate peripheral insulin resistance.Then,western blot and RT-PCR were used to detect the expression of IRS/PI3K/Akt,NF-?B signaling pathways and the downstream inflammatory factors in rats liver.Results:Vaspin significantly decreased serum FBG,FINS,TNF-? and IL-6 concentrations(P<0.05),while there were no significant affects on body weight,TG and TC levels(P>0.05).The area under curve of OGTT and ITT were significantly reduced when compared to the HFD group(P<0.05).There was an evident increase in glucose infusion rate in HFD+vaspin group(P<0.05).Compared with the HFD group,phosphorylated IRS-2 protein level was decreased and phosphorylated Akt,GLUT-2protein levels were increased after vaspin intervention(P<0.05).The expression of phosphorylated I?B? and NF-?B proteins were decreased,and the level of m RNA of downstream inflammatory factors TNF-? and IL-6 were reduced in HFD+vaspin group(P<0.05).Conclusion:Vaspin can promote the conduction of IRS/PI3K/Akt signaling pathway in rats liver,and improve insulin sensitivity,meanwhile vaspin can inhibit the expression of NF-?B signaling molecules,alleviate the body's inflammatory state,and improve insulin resistance,and ultimately reduce blood glucose.