The regulation of adipocyte metabolism and gene expression by interleukin-11

摘要

Diabetes in large part is a disease of muscle and adipose tissues; the inability of insulin to properly signal and stimulate the translocalion of the insulin-responsive glucose transporter leads to the clinical manifestation of hyperglycemia. In addition, adipose tissue has been identified as a site of synthesis and secretion of TNF-alpha, an inflammatory cytokine, which acting in an autocrine manner leads to insulin resistance. Inlerleukin-11 is an anti-inflammatory cytokine with receptors located on most cell types and tissues throughout the body. In a diabetic mouse model, administration of IL-11 resulted in maintenance of euglycemia in the absence of insulin. While the mechanism was not investigated, it was suggested that this effect was attributed to an alteration in the signaling pathway. IL-11 has also been demonstrated to turn off the synthesis of TNF-alpha. Thus, it becomes important to understand how IL-11 interacts with adipose and muscle tissues and initiates signal transdtiction. In this study, we began to examine IL-11 signaling in the 3T3-L1 adipocyte cell culture model. In the current study, we have demonstrated the presence and functionality of the IL-11 receptor in the 3T3-L1 adipocytes. Moreover, exposure of the adipocytes to IL-11 resulted in major alterations in gene expression, some of which occurred in adipose specific genes and those related to insulin action. Most importantly, it would appear that IL-11 treatment resulted in an alteration in the plasma membrane content ofglucose transport proteins and this could have a profound effect on the maintenance of euglycemia in the intact animal.