Effect Of ARB On Expression Of CD68 And MCP-1 In Adipose Tissue Of Rats On Long-term High-fat-diet

Objective:To explore the inflammatory changes in adipose tissue of rats on long-term high fat diet. To better understand the relationship between adipose tissue macrophage infiltration and insulin resistance (IR) and effect of angiotensin receptor blocker (ARB) on macrophage infiltration in adipose tissue of rats on Long-term hight-fat-diet. To further study the relationship of pimelitis and insulin resistance . To observe the effects of ARB intervention on macrophage infiltration in adipose tissueMethods:IR rat model was established by feeding high calorie and high-fat diet.Valsartan intervened from the 15th week to the 23rd week. The change of insulin sensitivity was valued by hyperinsulinemic euglycemic clamp. Inflammatory cell infiltration of adipose tissue were observed under light microscopes with hematoxylin and eosin (HE). The expression level of CD68 and MCP-1 protein in adipose tissue were examined by immunohistochemistry. Semiquantitative RT-PCR for detection of CD68 and MCP-1 mRNA. Serum insulin was analyzed by radioimmunoassay. TG and free fat acid were measured by biochemistry. Serum glucose was analyzed by One Touch blood glucose meter.Results:The level of intra-abdominal obesity, the content of visceral fat and inflammatory cells in local adipose tissue in experimental group were higher than that of in control group(P<0.01). In experimental group, serum triglyceride, free fatty acids and fasting serum insulin were significantly increased, meanwhile the insulin sensitivity was lower(P<0.01). The serum TG and FFA levels dropped in the HV group, but there was no significant difference between the HV group and HF group(P>0.05).Compared with the HF group,the relative amount of inflammatory cells within adipose tissue was decreased in NC and HV group. CD68 relative concentration was increased significantly for the HF (75.24±2.60 compared with 35.89±2.01 in NC, P<0.01) and was decreased significantly for the HV (47.48±2.33 compared with 75.24±2.60 in HF, P<0.01). MCP-1 relative concentration was increased significantly for the HF (82.75±0.99 compared with 51.93±1.73 in NC, P<0.01) and was decreased significantly for the HV (55.82±2.55 compared with 82.75±0.99 in HF, P<0.01) . Compared with the NC group, the CD68 and MCP-1 gene expression was increased to 2.6 times,2.1 times respectively(P<0.01)in HF group;They respectively decreased by 30%,27%(P<0.01) in HV group compared with HF .Correlative relationship between CD68 and the percentage of abdominal body fat , GIR60~120 ,MCP-1. CD68 was significantly and positively correlated with the percentage of abdominal body fat(r=0.834,P<0.01),and GIR60~120 negatively associated with CD68 expression (r=-0.874,P<0.01)abdominal body fat MCP-1 was significantly and positively correlated with CD68(r=0.797,P<0.01).Conclusion:There were pimelitis and insulin resistance in rat obesity induced by high calorie and high-fat diet. ARB can inhibit the infiltration of macrophages and expression of MCP-1 and then attenuate the inflammation and improve insulin resistance in rats. The serum TG and FFA levels dropped in the HV group, but there was no significant difference between the HV group and HF group...