Interleukin-6 is a positive regulator of tumor necrosis factor -induced adipose-related protein in 3T3-L1 adipocytes
Edited by Robert Barouki
Mathias Fasshauer a,
Kralisch a, 1, Margit Klier a, Ulrike Lossner a, Matthias Bluher a, Anne-Marie
Johannes Klein c
and Ralf Paschke , ,
a University of Leipzig, Department of Internal Medicine III, 04103, Leipzig, Germany
b UMR 7079 CNRS, Université Pierre et Marie Curie, Centre de Recherche Biomédicale des Cordeliers, 15 rue de l'Ecole de Médecine, 75270, Paris Cedex 06, France
c University of Lübeck, Department of Internal Medicine I, 23538, Lübeck, Germany
Received 23 December 2003; Revised 19 January 2004; accepted 22 January 2004. Available online 4 February 2004.
Tumor necrosis factor (TNF) -induced adipose-related protein (TIARP) is a novel TNF-stimulated protein in adipocytes. Besides TNF, 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 TNF but also by IL-6 which has been shown to be another important cytokine implicated in the pathogenesis of insulin resistance.
Author Keywords: Author Keywords: Adipocyte; Insulin resistance; Interleukin-6; Obesity; Tumor necrosis factor ; Tumor necrosis factor -induced adipose-related protein
IL-6, interleukin-6; IRS, insulin
receptor substrate; Jak, Janus kinase; MAP, mitogen-activated protein; PI,
phosphatidylinositol; TIARP, tumor necrosis factor -induced
adipose-related protein; TNF, tumor necrosis factor
1 These authors contributed equally to this work.