A paracrine loop between adipocytes and macrophages aggravates inflammatory changes -: Role of free fatty acids and tumor necrosis factor α
A paracrine loop between adipocytes and macrophages aggravates inflammatory changes -: Role of free fatty acids and tumor necrosis factor α
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DOI：
10.1161/01.atv.0000183883.72263.13
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发表时间：
2005-10-01
影响因子：
8.7
通讯作者：
Ogawa, Y
中科院分区：
文献类型：
--
作者：
Suganami, T;Nishida, J;Ogawa, Y
目的：体重增加与巨噬细胞浸润脂肪有关，提示巨噬细胞是肥胖脂肪组织炎症的重要来源。在这里，我们开发了一个在体外共培养系统组成的脂肪细胞和巨噬细胞和研究的分子机制，使这些细胞communication.Methods和结果-共培养分化的3 T3-L1脂肪细胞和巨噬细胞系RAW 264的结果在显着上调促炎细胞因子，如肿瘤坏死因子α（TNF-α），和下调脂联素的抑制细胞因子脂联素。这种炎症变化是由无直接接触的共培养诱导的，表明可溶性因子的作用。主要发生在巨噬细胞中的TNF-α的中和抗体抑制3 T3-L1中的炎症变化，表明TNF-α是脂肪细胞中炎症的主要巨噬细胞源性介质。相反，游离脂肪酸（FFA）可能是巨噬细胞中重要的脂肪细胞来源的炎症介质，因为棕榈酸盐（3 T3-L1释放的主要FFA）显著增加了RAW 264中TNF-α的产生。通过使用从肥胖ob/ob mice.Conclusions获得的肥大的3 T3-L1或脂肪基质血管部分，在共培养物中的炎症变化得到增强-我们假设脂肪细胞和巨噬细胞之间的涉及FFA和TNF-α的旁分泌环路建立了一个恶性循环，其加剧了脂肪组织中的炎症变化。
Objective - Weight gain is associated with infiltration of fat by macrophages, suggesting that they are an important source of inflammation in obese adipose tissue. Here we developed an in vitro coculture system composed of adipocytes and macrophages and examined the molecular mechanism whereby these cells communicate.Methods and Results - Coculture of differentiated 3T3-L1 adipocytes and macrophage cell line RAW264 results in the marked upregulation of proinflammatory cytokines, such as tumor necrosis factor alpha (TNF-alpha), and the downregulation of the antiinflammatory cytokine adiponectin. Such inflammatory changes are induced by the coculture without direct contact, suggesting the role of soluble factors. A neutralizing antibody to TNF-alpha, which occurs mostly in macrophages, inhibits the inflammatory changes in 3T3-L1, suggesting that TNF-alpha is a major macrophage-derived mediator of inflammation in adipocytes. Conversely, free fatty acids (FFAs) may be important adipocyte-derived mediators of inflammation in macrophages, because the production of TNF-alpha in RAW264 is markedly increased by palmitate, a major FFA released from 3T3-L1. The inflammatory changes in the coculture are augmented by use of either hypertrophied 3T3-L1 or adipose stromal vascular fraction obtained from obese ob/ob mice.Conclusions - We postulate that a paracrine loop involving FFAs and TNF-alpha between adipocytes and macrophages establishes a vicious cycle that aggravates inflammatory changes in the adipose tissue.