Effect Of Lifestyle Modification On Expression Of TNF-α And Receptors In The Adipose Tissue Of Rats With Insulin Resistance

Objective: To investigate the effects of lifestyle modification including diet intervention and exercise on the expression of TNF-αand receptors in the adipose tissue of rats with insulin resistance. Compare the effect of improve insulin sensitivity of insulin resistance rat by diet intervention and exercise and explore the possible mechanism involved.Methods: Fifty healthy male SPF Wistar rats were randomly divided into two groups taking either high-fat diet(HF, n=39) or normal chow(NC, n=11). Eighteen weeks later, Selected 5 rats from each of two groups respectively,insulin sensitivity was measured with euglycemic-hyperinsulinemic clamp technique and analyzed the correlation between the glucose infusion rate (GIR) and fasting insulin. Evaluated insulin sensitivity of the other rats with FINS.34 high-fat fed rats were randomly divided into 4 groups by different interventions: high-fat fed group(n=8), swimming group(n=10),diet intervention group(n=6), diet intervention and swimming group(n=10). Six weeks later, sacrificed the rats. Blood samples were obtained and tissue were dissected.Some parameters were measured: (1) the length and the weight of the rats,the weight of adipose tissue; the level of fasting blood glucose (FBG), fasting insulin (FINS), triglyceride (TG), total cholesterol (TC), free fatty acid (FFA) in the serum (2)serum TNF-αconcentration; (3) the level of TNF-αmRNA,TNFR1mRNA,TNFR2mRNA in adipose tissue with the method of RT-PCR.(4) the level of TNF-α, TNFR1 protein in adipose tissue with the method of western blotting.Results: Compared to normal control group, the level of weight,FBG, FINS, TG, TC and FFA were obviously higher(P<0.05)and the GIR was obviously lower(P<0.01)in HF group for eighteen weeks. The GIR was negatively correlated with the FINS strongly (r=- 0.898,P=0.000). Compared to normal control group, the level of serum TNF-αand TNF-αmRNA, TNF-αprotein in adipose tissue were higher, the level of TNFR1mRNA,TNFR2mRNA and TNFR1 protein in adipose tissue were higher. Compared to HF group,Metabolism Markers were obviously reduce by exercise,but have no obviously reduce by diet intervention.Serum TNF-αconcentration was obviously reduce by exercise and diet intervention.The level of mRNA and protein of TNF-αand TNFR1 increased in exercise group,reduced in diet intervention and exercise group. The level of TNFR2mRNA in adipose tissue had no change in each group.Conclusion:High-fat diet induced insulin resistance in rats with the high expression of TNF-αand receptors in adipose tissue.Exercise could improve insulin sensitivity of insulin resistance rat by adjusting the lipids metabolism in adipose tissue through TNF-α.Diet intervention could improve insulin sensitivity of insulin resistance rat through Raducing TNF-αdirectly. Exercise is major means of lifestyle modification controling insulin resistance.