A unique role of monocyte chemoattractant protein 1 among chemokines in adipose tissue of obese subjects
A unique role of monocyte chemoattractant protein 1 among chemokines in adipose tissue of obese subjects
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DOI：
10.1210/jc.2005-0369
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发表时间：
2005-10-01
影响因子：
5.8
通讯作者：
Arner, P
中科院分区：
文献类型：
--
作者：
Dahlman, I;Kaaman, M;Arner, P
背景：脂肪组织中的低度炎症可能导致肥胖中的胰岛素抵抗。然而，个体炎症介质在脂肪组织中的作用却鲜为人知。
目的：本研究的目的是确定在人类肥胖中脂肪组织的基因水平上哪些炎症标志物过度表达最为显著，以及这与相应的蛋白质分泌有何关联。
设计：我们检测了17名消瘦者和20名肥胖者的基因表达谱。在几个肥胖或消瘦队列中，在体外和体内对人皮下脂肪组织或分离的脂肪细胞中相关相应蛋白质的分泌模式进行了检测。
结果：在对基因表达进行排序时，与肥胖以及免疫和防御反应相关的特定通路得分较高。在7种显著过度表达的趋化因子中，只有单核细胞趋化蛋白1（MCP1）在体外从脂肪组织和分离的脂肪细胞中释放出来。在肥胖症中，脂肪组织块中MCP1的分泌和表达分别增加了6倍多和2倍多，但循环中MCP1水平没有变化。体内从脂肪组织到循环中没有MCP1的净释放，但有瘦素的净释放。
结论：肥胖与脂肪组织中几种趋化因子基因的表达增加有关。然而，只有MCP1分泌到细胞外空间，在那里它主要作为一种局部因子起作用，因为很少或没有溢出到循环中。MCP1影响脂肪细胞的功能，是巨噬细胞的募集因子，并且可能是脂肪组织炎症和胰岛素抵抗之间趋化因子的关键联系。
Context: Low-grade inflammation in adipose tissue may contribute to insulin resistance in obesity. However, the roles of individual inflammatory mediators in adipose tissue are poorly understood.Objectives: The objective of this study was to determine which inflammation markers are most overexpressed at the gene level in adipose tissue in human obesity and how this relates to corresponding protein secretion.Design: We examined gene expression profiles in 17 lean and 20 obese subjects. The secretory pattern of relevant corresponding proteins was examined in human sc adipose tissue or isolated fat cells in vitro and in vivo in several obese or lean cohorts.Results: In ranking gene expression, defined pathways associated with obesity and immune and defense responses scored high. Among seven markedly overexpressed chemokines, only monocyte chemoattractant protein 1 (MCP1) was released from adipose tissue and isolated fat cells in vitro. In obesity, the secretion and expression of MCP1 in adipose tissue pieces were more than 6- and 2-fold increased, respectively, but there was no change in circulating MCP1 levels. There was no net release of MCP1, but there was a net release of leptin, in vivo from adipose tissue into the circulation.Conclusions: Obesity is associated with the increased expression of several chemokine genes in adipose tissue. However, only MCP1 is secreted into the extracellular space, where it primarily acts as a local factor, because little or no spillover into the circulation occurs. MCP1 influences the function of adipocytes, is a recruitment factor for macrophages, and may be a crucial link among chemokines between adipose tissue inflammation and insulin resistance.