Superantigen activates the gp130 receptor on adipocytes resulting in altered adipocyte metabolism
Superantigen activates the gp130 receptor on adipocytes resulting in altered adipocyte metabolism
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DOI：
10.1016/j.metabol.2014.03.004
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发表时间：
2014-06-01
影响因子：
9.8
通讯作者：
Nilson, Bo
中科院分区：
文献类型：
--
作者：
Banke, Elin;Rodstrom, Karin;Nilson, Bo
客观的。金黄色葡萄球菌是正常菌群的一部分，产生一系列肠毒素，可导致食物中毒和中毒性休克，并可能导致炎症性疾病的发病机制。这些肠毒素直接将 T 细胞受体与 MHC II 类交联，激活大量 T 细胞，因此被称为超抗原。最近发现超抗原SEA与细胞因子受体gp130结合。由于肥胖和 2 型糖尿病与脂肪组织炎症高度相关，并且 gp130 已被证明在脂肪细胞中发挥重要作用，因此我们想要研究 SEA 对脂肪细胞信号传导和功能的影响。材料/方法。在无细胞系统中使用表面等离子体共振检查SEA与gp130的结合。使用蛋白质印迹法和脂肪分解、脂肪生成和葡萄糖摄取的生物测定法研究SEA对脂肪细胞信号传导、胰岛素敏感性和功能的影响。结果。我们证明 SEA 以中等亲和力与 gp130 结合。此外，SEA 诱导脂肪细胞中关键下游靶标 STAT3 的磷酸化。 SEA 还抑制胰岛素诱导的 PKB 激活和 PKB 下游信号传导，该信号与基础和胰岛素诱导的葡萄糖摄取减少、脂肪生成减少以及胰岛素抑制脂肪分解的能力降低有关。结论。 SEA 抑制脂肪细胞中的胰岛素信号传导和胰岛素生物反应，支持细菌感染可能导致胰岛素抵抗和 2 型糖尿病的发生。 (C) 2014 Elsevier Inc. 保留所有权利。
Objective. The bacteria Staphylococcus aureus is part of the normal bacterial flora and produces a repertoire of enterotoxins which can cause food poisoning and toxic shock and might contribute to the pathogenesis of inflammatory diseases. These enterotoxins directly cross-link the T cell receptor with MHC class II, activating large amounts of T cells and are therefore called superantigens. It was recently discovered that the superantigen SEA binds to the cytokine receptor gp130. As obesity and type 2 diabetes are highly associated with inflammation of the adipose tissue and gp130 has been shown to play an important role in adipocytes, we wanted to investigate the effect of SEA on adipocyte signaling and function.Materials/methods. Binding of SEA to gp130 was examined using surface plasmon resonance in a cell free system. Effects of SEA on adipocyte signaling, insulin sensitivity and function were studied using western blotting and biological assays for lipolysis, lipogenesis and glucose uptake.Results. We demonstrate that SEA binds to gp130 with a medium affinity. Furthermore, SEA induces phosphorylation of a key downstream target, STAT3, in adipocytes. SEA also inhibits insulin-induced activation of PKB and PKB downstream signaling which was associated with reduced basal and insulin induced glucose uptake, reduced lipogenesis as well as reduced ability of insulin to inhibit lipolysis.Conclusions. SEA inhibits insulin signaling as well as insulin biological responses in adipocytes supporting that bacterial infection might contribute to the development of insulin resistance and type 2 diabetes. (C) 2014 Elsevier Inc. All rights reserved.