Interleukin‐6 is a positive regulator of tumor necrosis factor α‐induced adipose‐related protein in 3T3‐L1 adipocytes

Abstract

Tumor necrosis factor (TNF) α‐induced adipose‐related protein (TIARP) is a novel TNFα‐stimulated protein in adipocytes. Besides TNFα, interleukin (IL)‐6 has recently been shown to be another adipocytokine implicated in insulin resistance. Therefore, the impact of IL‐6 on TIARP gene expression in 3T3‐L1 adipocytes was determined by quantitative real‐time reverse transcription‐polymerase chain reaction. Interestingly, TIARP mRNA expression was stimulated up to 3.8‐fold by IL‐6 in a dose‐dependent fashion with significant stimulation detectable at effector concentrations as low as 3 ng/ml and maximal effects seen at 100 ng/ml IL‐6. Induction of TIARP mRNA by IL‐6 was time‐dependent with significant upregulation occurring as early as 2 h after effector addition and maximal effects observed at 4 h. In parallel, TIARP protein synthesis was upregulated with maximal effects seen after 8 h of IL‐6 treatment. Furthermore, the Janus kinase 2 inhibitor AG490 decreased TIARP mRNA expression. The increase of TIARP mRNA could be reversed by withdrawal of IL‐6 for 24 h. Furthermore, TIARP mRNA induction by IL‐6 was also seen in brown adipocytes but not in muscle and liver cells. Taken together, these results show that TIARP is acutely regulated in adipose tissue not only by TNFα but also by IL‐6 which has been shown to be another important cytokine implicated in the pathogenesis of insulin resistance.