Ursolic acid induces the production of IL6 and chemokines in both adipocytes and adipose tissue

Abstract

ABSTRACT Adipose tissue inflammation plays an important role in the regulation of glucose and lipids metabolism. It is unknown whether Ursolic acid (UA) could regulate adipose tissue inflammation, though it can regulate inflammation in many other tissues. In this study, 3T3-L1 adipocytes, DIO mice and lean mice were treated with UA or vehicle. Gene expression of inflammatory factors, chemokines and immune markers in adipocytes and adipose tissue, cytokines in cell culture medium and serum, and inflammation regulatory pathways in adipocytes were detected. Results showed that UA increased the expression of interleukins and chemokines, but not TNFα, in both adipocytes and adipose tissue. IL6 and MCP1 levels in the cell culture medium and mouse serum were induced by UA treatment. Cd14 expression level and number of CD14+ monocytes were higher in UA treated adipose tissue than those in the control group. Glucose tolerance test was impaired by UA treatment in DIO mice. Mechanistically, UA induced the expression of Tlr4 and the phosphorylation levels of ERK and NFκB in adipocytes. In conclusion, our study indicated that short-term UA administration could induce CD14+ monocytes infiltration by increasing the production of interleukins and chemokines in mouse adipose tissue, which might further impair glucose tolerance test.