Tumor necrosis factor α is a negative regulator of resistin gene expression and secretion in 3T3-L1 adipocytes
Tumor necrosis factor α is a negative regulator of resistin gene expression and secretion in 3T3-L1 adipocytes
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DOI：
10.1006/bbrc.2001.5874
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发表时间：
2001-11-09
影响因子：
3.1
通讯作者：
Paschke, R
中科院分区：
文献类型：
--
作者：
Fasshauer, M;Klein, J;Paschke, R
抵抗素最近被认为是导致胰岛素抵抗的脂肪细胞因子，因此可能与肥胖和糖尿病有关。为了进一步表征胰岛素敏感性调节激素对这种脂肪分泌蛋白的调节作用，我们用肿瘤坏死因子(TNF) α、血管紧张素（AT） 2和生长激素（GH）处理3T3-L1脂肪细胞，并通过定量实时逆转录-聚合酶链反应和Western blotting检测抵抗素基因表达和蛋白分泌。有趣的是，TNF α治疗后，抵抗素mRNA表达和蛋白分泌均被抑制70-90%，而AT2和GH没有任何影响。TNF - α的抑制作用是时间和剂量依赖性的，早在效应剂加入后4小时，浓度低至1 ng/ml TNF - α时就出现了显著的抑制作用。蛋白激酶A （PKA）、p44/42和p38丝裂原活化蛋白（MAP）激酶的药理抑制并没有逆转TNF α的抑制作用，这表明这些信号分子都没有参与TNF α对抵抗素基因表达的抑制。此外，通过停用TNF α 24小时，抵抗素mRNA水平的抑制可以完全逆转到控制水平。综上所述，这些结果表明TNF α是抵抗素基因表达的关键负调控因子。这可能对胰岛素抵抗的发病机制及其与肥胖的联系具有重要意义。(C) 2001学术出版社。
Resistin has recently been implicated as an adipocytokine leading to insulin resistance and, therefore, potentially linking obesity and diabetes. To further characterize the regulation of this fat-secreted protein by insulin sensitivity-modulating hormones, 3T3-L1 adipocytes were treated with tumor necrosis factor (TNF) alpha, angiotensin (AT) 2, as well as growth hormone (GH), and resistin gene expression and protein secretion were determined by quantitative real-time reverse transcription-polymerase chain reaction and Western blotting. Interestingly, both, resistin mRNA expression and protein secretion, were inhibited by 70-90% after TNF alpha -treatment whereas AT2 and GH did not have any effect. The inhibitory effect of TNF alpha was time- and dose-dependent with significant inhibition occurring as early as 4 h after effector addition and at concentrations as low as I ng/ml TNF alpha. Pharmacological inhibition of protein kinase A (PKA), p44/42, and p38 mitogen-activated protein (MAP) kinase did not reverse the inhibitory effect of TNF alpha suggesting that neither of these signaling molecules is involved in suppression of resistin gene expression by TNF alpha. Furthermore, suppression of resistin mRNA levels could be completely reversed to control levels by withdrawal of TNF alpha for 24 h. Taken together, these results suggest that TNF alpha is a pivotal negative regulator of resistin gene expression. This may have important implications for the pathogenesis of insulin resistance and its link to obesity. (C) 2001 Academic Press.