Monocyte chemotactic protein-1 is a potential player in the negative cross-talk between adipose tissue and skeletal muscle
Monocyte chemotactic protein-1 is a potential player in the negative cross-talk between adipose tissue and skeletal muscle
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DOI：
10.1210/en.2005-0969
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发表时间：
2006-05-01
期刊：
影响因子：
4.8
通讯作者：
Eckel, J
中科院分区：
文献类型：
--
作者：
Sell, H;Dietze-Schroeder, D;Eckel, J
脂肪组织是一个主要的分泌和内分泌活跃器官，产生多种生物活性蛋白，可能调节能量代谢和胰岛素敏感性。在几项研究中，我们已经证明脂肪细胞分泌产物诱导骨骼肌胰岛素抵抗。然而，这些因素的确切性质仍然难以捉摸。人类脂肪细胞可分泌多种细胞因子，包括IL-6、IL-8、巨噬细胞炎性蛋白-1α/β和单核细胞趋化蛋白-1(MCP-1)。在这些候选者中，MCP-1单独在与其生理血浆浓度(200pg/ml)相似的剂量下损害骨骼肌细胞中的胰岛素信号，而IL-6、IL-8和巨噬细胞炎性蛋白-1β仅在非常高的浓度下有效。此外，单核细胞趋化蛋白-1显著降低胰岛素刺激的心肌细胞葡萄糖摄取。对骨骼肌细胞趋化因子受体表达的分析表明，骨骼肌细胞存在趋化因子CXC基序受体1/2和趋化因子CC基序受体1/2/4/5/10。MCP-1对骨骼肌细胞胰岛素信号转导的作用是通过ERK1/2激活实现的，但不涉及核因子-kappa B通路的激活。综上所述，我们的数据表明脂肪细胞分泌各种脂肪因子，这些脂肪因子可能参与了脂肪组织和骨骼肌之间的负串扰。人类骨骼肌细胞对MCP-1高度敏感，当MCP-1的浓度低于循环中的浓度时，MCP-1会损害胰岛素信号和葡萄糖摄取。然而，脂肪细胞释放的其他细胞因子只有在超生理浓度时才会削弱胰岛素的作用。因此，MCP-1可能代表了脂肪组织和骨骼肌之间负相关的分子联系，赋予了MCP-1除炎症以外全新的重要作用。
Adipose tissue is a major secretory and endocrine active organ producing a variety of bioactive proteins that may regulate energy metabolism and insulin sensitivity. In several studies, we have already shown that adipocyte-secretory products induce skeletal muscle insulin resistance. However, the precise nature of these factors has remained elusive. Human adipocytes were found to secrete various cytokines including IL-6, IL-8, macrophage inflammatory protein-1 alpha/beta, and monocyte chemotactic protein-1 (MCP-1). Among these candidates, MCP-1 alone impaired insulin signaling in skeletal muscle cells at doses similar to its physiological plasma concentrations ( 200 pg/ml), whereas IL-6, IL-8, and macrophage inflammatory protein-1 beta were effective at very high concentrations only. In addition, MCP-1 significantly reduced insulin-stimulated glucose uptake in the myocytes. Expression analysis of chemokine receptors in skeletal muscle cells revealed the presence of chemokine CXC motif receptor 1/2 and chemokine CC motif receptor 1/2/4/5/10. The action of MCP-1 on insulin signaling in skeletal muscle cells occurs via ERK1/2 activation but does not involve activation of the nuclear factor kappa B pathway. In conclusion, our data show that adipocytes secrete various adipokines that maybe involved in the negative crosstalk between adipose tissue and skeletal muscle. Human skeletal muscle cells are highly sensitive toward MCP-1, which impairs insulin signaling and glucose uptake at concentrations even below that found in the circulation. However, other cytokines that are released by adipocytes impair insulin action only at supraphysiological concentrations. Therefore, MCP-1 may represent a molecular link in the negative crosstalk between adipose tissue and skeletal muscle assigning a completely novel important role to MCP-1 besides inflammation.