The Role Of CCL5 In Obesity-induced Adipose Tissue Inflammation And Insulin Resistance

Objective:As a typical chemokine,CCL5 has been shown to infiltrate T cells and macrophages into inflammatory sites in a variety of diseases.CCL5 has been shown to be elevated in obese adipose tissue,but the roles and mechanisms of CCL5 receptor-CCR5 actions in adipose tissue inflammation and insulin resistance remain under debate.Whether CCL5 can promote adipose tissue inflammation and insulin resistance in obese mice remains unclear.Our study aims to investigate the role of CCL5 in the development of obesity and its complications.Methods:First,the expression of CCL5 and its receptors in the important metabolic tissues(visceral fat,skeletal muscle,liver)of lean and obese C57 mice was detected to determine the main target organs of CCL5 in obesity.The proportion of CCL5 expression in different cells in the SVF of adipose tissue of lean and obese mice was further detected to determine the main source of CCL5 in adipose tissue of obese mice.To determine the effects of CCL5 gene blockade on insulin sensitivity and glucose tolerance in physiological and obesity-pathologic states,we examined body weight and metabolic phenotypes of WT and CCL5 KO mice in the normal diet group and the high-fat diet group.To examine the role of CCL5 in adipose tissue inflammation associated with obesity,the infiltration of inflammatory cells in adipose tissue of CCL5 gene knockout mice was detected by flow cytometry and q PCR.Results:1.The increased expression of CCL5 in visceral adipose tissue of obese mice was mainly enriched in CD8~+T cells.2.CCL5 deficiency did not affect the body weight of mice,but aggravated obesity-induced insulin resistance and liver steatosis.3.CCL5 deficiency increased T cell infiltration in adipose tissue of obese mice.4.CCL5 deficiency resulted in increased T cell-associated chemokin-e signaling in visceral adipose tissue of obese mice.Conclusion:CCL5 deficiency cannot inhibit obesity-induced adipose tissue inflammation and glucose metabolism disorder,but promotes T cell infiltration in visceral adipose tissue,further aggravates adipose tissue inflammation and damages systemic insulin sensitivity.The possible mechanism is that CCL5 knockout leads to compensatory increase of chemokine signaling in adipose tissue T cells.