Monocyte chemoattractant protein-1 release is higher in visceral than subcutaneous human adipose tissue (AT): Implication of macrophages resident in the AT
Monocyte chemoattractant protein-1 release is higher in visceral than subcutaneous human adipose tissue (AT): Implication of macrophages resident in the AT
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DOI：
10.1210/jc.2004-1696
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发表时间：
2005-04-01
影响因子：
5.8
通讯作者：
Richelsen, B
中科院分区：
文献类型：
--
作者：
Bruun, JM;Lihn, AS;Richelsen, B
人脂肪组织（AT）可产生包括单核细胞趋化蛋白1（MCP-1）在内的多种脂肪因子，参与动脉粥样硬化的发病机制。目的：以人AT培养物、脂肪细胞和间质血管细胞为材料，研究AT驻留巨噬细胞、MCP-1与肥胖的关系及MCP-1的调节作用。巨噬细胞特异性标志物CD 68和CD 14的mRNA水平与皮下AT和内脏AT的肥胖程度相关（P < 0.05）。MCP-1的产生在基质-血管细胞中高于脂肪细胞（P < 0.01），并且与AT隔室中的巨噬细胞标志物相关（P < 0.05）。MCP-1释放在肥胖受试者（P < 0.05）和VAT受试者（P < 0.01）中较高，但在调整AT驻留巨噬细胞后，差异消失。MCP-1受IL-1 β、TNF-α、IL-8、IL-4和IL-6 + IL-6可溶性受体的刺激，并受地塞米松、IL-10、二甲双胍和噻唑烷二酮类药物的抑制。尽管如此，MCP-1可能与肥胖相关的健康并发症有关，二甲双胍和噻唑烷二酮降低MCP-1表明这些抗糖尿病化合物具有改善肥胖症中观察到的低度炎症状态的抗糖尿病特性。
Human adipose tissue (AT) produces several adipokines including monocyte chemoattractant protein (MCP)-1, involved in the pathogenesis of atherosclerosis.Objective: Human AT cultures, isolated adipocytes, and stromal-vascular cells were used to investigate the relationship among AT-resident macrophages, MCP-1, and adiposity and the regulation of MCP-1.Results: mRNA levels of specific macrophage markers (CD68 and CD14) are correlated with adiposity in sc AT and visceral AT (P < 0.05). MCP-1 production is higher in stromal-vascular cells vs. adipocytes (P < 0.01) and correlates with macrophage markers in both AT compartments (P < 0.05). MCP-1 release is higher in obese subjects (P < 0.05) and in VAT (P < 0.01), but after adjusting for AT-resident macrophages, the differences disappear. MCP-1 is stimulated by IL-1 beta, TNF-alpha, IL-8, IL-4, and IL-6 + IL-6-soluble receptor and is decreased by dexamethasone, IL-10, metformin, and thiazolidinediones.Discussion: MCP-1 is correlated with specific macrophage markers, adiposity, and AT localization, but the relationship seems to be related to the number of AT-resident macrophages. Despite this, MCP-1 may be involved in obesity-related health complications, and the decrease of MCP-1 by metformin and thiazolidinediones suggests that these antidiabetic compounds have antiinflammatory properties improving the low-grade inflammatory state observed in obesity.