Serum amyloid A3 expression is stimulated by dexamethasone and interleukin-6 in 3T3-L1 adipocytes
Serum amyloid A3 expression is stimulated by dexamethasone and interleukin-6 in 3T3-L1 adipocytes
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DOI：
10.1677/joe.1.05699
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发表时间：
2004-12-01
影响因子：
4
通讯作者：
Paschke, R
中科院分区：
文献类型：
--
作者：
Fasshauer, M;Klein, J;Paschke, R
急性期反应物的全身水平的慢性增加有助于胰岛素抵抗和相关疾病如心血管疾病的发展。最近，血清淀粉样蛋白A3（SAA 3）已被确定为脂肪细胞分泌的急性期反应物，其表达在胰岛素抵抗和肥胖中显著增加。为了进一步阐明这种脂肪细胞因子在脂肪中的表达和调节，在3 T3-L1脂肪细胞分化期间以及用已知诱导胰岛素抵抗和促成动脉粥样硬化的各种激素处理后，通过定量实时逆转录酶PCR测量SAA 3 mRNA。SAA 3 mRNA在3 T3-L1前脂肪细胞分化过程中显著诱导高达77倍。此外，100 nM地塞米松和30 ng/ml白细胞介素（IL）-6以时间依赖性方式分别诱导SAA 3 mRNA高达11倍和4.8倍，在低至10 nM地塞米松和1 ng/ml IL-6的浓度下观察到显著刺激。相反，胰岛素，异丙肾上腺素和生长激素不影响SAA 3的合成。抑制剂研究表明IL-6对SAA 3表达的积极作用至少部分由Janus激酶2介导。总之，我们的研究结果表明糖皮质激素和IL-6对SAA 3的差异调节支持了这种急性期反应物在胰岛素抵抗发病机制中的综合作用及其与肥胖和心血管疾病的联系。
A chronic increase in systemic levels of acute-phase reactants contributes to the development of insulin resistance and associated disorders such as cardiovascular disease. Recently, serum amyloid A3 (SAA3) has been characterized as an adipocyte-secreted acute-phase reactant, expression of which is dramatically increased in insulin resistance and obesity. To further clang, expression and regulation of this adipocytokine in fat, SAA3 mRNA was measured by quantitative real-time reverse transcriptase PCR during differentiation of 3T3-L1 adipocytes and after treatment with various hormones known to induce insulin resistance and contribute to atherosclerosis. SAA3 mRNA was dramatically induced up to 77-fold during differentiation of 3T3-L1 preadipocytes. Furthermore, 100 nM dexamethasone and 30 ng/ml interleukin (IL)-6 induced SAA3 mRNA by up to 11- and 4.8-fold, respectively, in a time-dependent fashion with significant stimulation observed at concentrations as low as 10 nM dexamethasone and 1 ng/ml IL-6. In contrast, insulin, isoproterenol and growth hormone did not influence SAA3 synthesis. Inhibitor studies suggested that the positive effect of IL-6 on SAA3 expression is at least in part mediated by Janus kinase 2. Taken together, our results show a differential regulation of SAA3 by glucocorticoids and IL-6 supporting an integrative role of this acute-phase reactant in the pathogenesis of insulin resistance and its link to obesity and cardiovascular disease.