The Expression Of Visfatin Gene In High-Fat Fed Rats And The Effect Of Blockade Of RAS On It

ObjectiveTo explore the expression of visfatin mRNA in the high-fat chow fed rats and theeffect of blockade the Renin–angiotensin system (RAS) on it, and to investigate therelations between visfatin,RAS andinsulinresistance. Tofurtherstudythepathogenesis ofinsulinresistanceandmolecularmechanismsofinsulinresistanceprevention.MethodsThirty male rats were divided into 3 groups: normal control (NC group, n=10),high-caloric and high-fat diet fed (HF group, n=10) and valsartan intervened (HV group,n=10).TheNCgroupratswerefedwithcommondietfor20weeks.TheHFgroupandHVgroupratswerefedwithhighfatdietcontaining46%saturatedfreefattyacidfor20weeks.The HV group began valsartan intervened (40mg*kg-1*d-1) from 15th week to 23th week.The change of insulin sensitivity was evaluated by euglycemic-hyperinsulinemic clamp.RT-PCR was employedtostudyvisfatin,AGTandGLUT4gene expressions in epididymalfat tissue of rats with different diets and effects of valsartan on them. Blood glucose,triglyceride and free fatty acids (FFAs) were detected by corresponding oxidase method.Insulinsecretionwasdetectedbyradioimmunoassaytechnique.ResultsCompared with the NC group, glucose infusion rate in HF group was reducedsignificantly(GIR11.3±2.7vs.4.8±1.4P<0.01),thebodyweight,theratioofepididymalfat weight tobodyweight andthefastingserum levels ofinsulin,triglyceride,freefat acids(FFAs) were significantly higher than those in the control (P<0.01). Visfatin and AGTmRNA expression in the epididymal fat tissue were increased significantly (P<0.01), GLUT4 mRNA expression in the epididymal fat tissue was decreased significantly in HFgroupcomparedwiththecontrol(P<0.01).Compared with the HF group, glucose infusion rate in HV group was increasedsignificantly (GIR 8.5±1.9 vs.4.8±1.4 P<0.01), but the ratio of epidimal fat weight tobody weight and the fasting serum levels of insulin decreased significantly (P<0.01).Visfatin and AGT mRNA expression in the epididymal fat tissue was decreasedsignificantlyinHVgroup(P<0.01), GLUT4mRNAexpressionintheepididymal fat tissuewasincreasedcomparedwiththeHFgrouprats(P<0.01).ConclusionHigh-caloric and high-fat diet can induce insulin resistance in rats. The expression ofRenin-angiotensin-system was increased compared with normal control rats. The ARBdrugs canameliorateinsulinresistancethroughblockedtheRAS.Thedifferenceofvisfatinand GLUT4 expression in the epididymal fat tissue were correlated with insulin resistance.The RAS blockade can increase the expression of visfatin and GLUT4, which may be oneof the mechanisms involved in the improvement of insulin resistance. Visfatin is expressedin the epididymal fat tissue of rats and the expressed level varied in different diet rats.Visfatin was up-regulated in rats with high-caloric and high-fat diet. High fat feedinginduces insulin resistance. Visfatin mRNA expression is augmented in the epididymal fattissue of high-caloric and high-fat fed rats. The blockade of RAS can ameliorate insulinresistance, can lower the expression of visfatin in epididymal fat tissue. Visfatin mayfunction as an autocrine and paracrine factor in abdominal fat tissue. The increase ofvisfatin mRNA might be related to insulin resistance in the abdominal fat tissue. Visfatinmay transmit important signal(s) to the abdominal fat tissue itself or to remote organs andmayactasanantecedentsignalofinsulinresistance.