Adiponectin gene expression and secretion is inhibited by interleukin-6 in 3T3-L1 adipocytes
Adiponectin gene expression and secretion is inhibited by interleukin-6 in 3T3-L1 adipocytes
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DOI：
10.1016/s0006-291x(03)00090-1
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发表时间：
2003-02-21
影响因子：
3.1
通讯作者：
Paschke, R
中科院分区：
文献类型：
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作者：
Fasshauer, M;Kralisch, S;Paschke, R
最近，已经显示脂联素是重要的胰岛素增敏性脂肪来源蛋白，其在胰岛素抵抗和肥胖中下调，并且其补充改善胰岛素敏感性。相反，白细胞介素（IL）-6作为脂肪细胞因子出现，其血清浓度在这些状态下升高。然而，尚未确定IL-6是否可能影响脂联素的表达和分泌。为了阐明这一点，用不同浓度的IL-6处理3 T3-L1脂肪细胞不同的时间段。通过实时定量逆转录聚合酶链反应测定脂联素mRNA，并通过放射免疫分析测定分泌。有趣的是，用30 ng/ml IL-6处理3 T3-L1细胞显著降低脂联素分泌至对照水平的75%。用毛喉素（50 μ M）、肿瘤坏死因子a（100 ng/ml）和地塞米松（100 nM）长期治疗也可抑制脂联素分泌25%-45%。此外，脂联素mRNA表达下调高达50%的时间和剂量依赖性的方式，与显著的抑制检测浓度低至3 ng/ml IL-6和效应器添加后8小时。用p44/42丝裂原活化蛋白（MAP）激酶的药理学抑制剂预处理3 T3-L1细胞可部分逆转IL-6的抑制作用。IL-6对脂联素mRNA表达的抑制作用可被停药24 h所逆转。两者合计，我们的研究结果表明，脂联素基因的表达是可逆性下调IL-6和支持的概念脂联素是一个重要的选择性控制调节胰岛素敏感性。(C)2003 Elsevier Science（美国）。All rights reserved.
Recently, it has been shown that adiponectin is an important insulin-sensitizing fat-derived protein which is downregulated in insulin resistance and obesity, and replenishment of which improves insulin sensitivity. In contrast, interleukin (IL)-6 appears as an adipocytokine serum concentrations of which are elevated in these states. However, it has not been determined whether IL-6 might impact on expression and secretion of adiponectin. To clarify this, 3T3-L1 adipocytes were treated with different concentrations of IL-6 for various periods of time. Adiponectin mRNA was measured by quantitative real-time reverse transcription-polymerase chain reaction and secretion was determined by radioimmunoassays. Interestingly, treatment of 3T3-L1 cells with 30ng/ml IL-6 significantly decreased adiponectin secretion to 75% of control levels. Adiponectin secretion was also inhibited between 25% and 45% by chronic treatment with forskolin (50muM), tumor necrosis factor a (100ng/ml), and dexamethasone (100nM). Furthermore, adiponectin mRNA expression was downregulated by up to 50% in a time- and dose-dependent manner, with significant inhibition detectable at concentrations as low as 3ng/ml IL-6 and as early as 8 h after effector addition. The inhibitory effect of IL-6 was partially reversed by pretreatment of 3T3-L1 cells with pharmacological inhibitors of a p44/42 mitogen-activated protein (MAP) kinase. Moreover, the negative effect of IL-6 on adiponectin mRNA expression could be reversed by withdrawal of the hormone for 24h. Taken together, our results suggest that adiponectin gene expression is reversibly downregulated by IL-6 and support the concept of adiponectin being an important selectively controlled modulator of insulin sensitivity. (C) 2003 Elsevier Science (USA). All rights reserved.