FEBS Letters Volume 560, Issues 1-3 , 27 February 2004, Pages 153-157

doi:10.1016/S0014-5793(04)00096-1     Cite or link using doi  
Copyright © 2004 Federation of European Biochemical Societies. Published by Elsevier Science B.V.

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, 1}, Susan Kralisch ^{a, 1}, Margit Klier ^a, Ulrike Lossner ^a, Matthias Bluher ^a, Anne-Marie Chambaut-Guérin ^b, Johannes Klein ^c and Ralf Paschke <sup>, , a

a</sup> 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.

Abstract

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