Monocyte chemoattractant protein-1 and nitric oxide promote adipogenesis in a model that mimics obesity
Monocyte chemoattractant protein-1 and nitric oxide promote adipogenesis in a model that mimics obesity
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DOI：
10.1038/oby.2007.352
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发表时间：
2007-12-01
期刊：
影响因子：
6.9
通讯作者：
Morrison, Wayne A.
中科院分区：
文献类型：
--
作者：
Hemmrich, Karsten;Thomas, Gregory P. L.;Morrison, Wayne A.
目的：越来越多的证据表明脂肪形成与炎症有关。肥胖，单独或作为代谢综合征的一部分，其特征在于慢性低水平炎症状态，如炎性细胞因子和急性期蛋白质的血浆水平升高所揭示的。如果炎症可以反过来增加脂肪组织的生长，这可能是肥胖症正反馈循环的基础。我们已经开发了一种用于在小鼠中生长脂肪组织的组织工程模型，该模型允许量化脂肪生成的增加。在这项研究中，我们评估了成脂潜力的炎症原单核细胞趋化蛋白（MCP）-1和Zymosan-A（Zy）在小鼠组织工程model.Research方法和程序：MCP-1和Zy被添加到充满基质胶和成纤维细胞生长因子2的腔室。分析诱导型一氧化氮合酶（iNOS）的作用，iNOS抑制剂aminoguanidine被添加到chamber.Results：我们的研究结果表明，MCP-1产生成比例的大量新的脂肪组织。这种新脂肪形成伴随着巨噬细胞的向内生长，并且可以被Zy模仿。Aminoguanidine显着抑制脂肪tissue.Discussion的形成：我们的研究结果表明，低度炎症和诱导型一氧化氮合酶的表达是脂肪形成的重要因素。由于肥胖和代谢综合征中的脂肪新生被认为是由巨噬细胞衍生的促炎细胞因子介导的，因此这种脂肪组织工程系统提供了一种可能用于进一步阐明这两种代谢紊乱的发病机制的模型。
Objective: An increasing body of evidence is emerging linking adipogenesis and inflammation. Obesity, alone or as a part of the metabolic syndrome, is characterized by a state of chronic low-level inflammation as revealed by raised plasma levels of inflammatory cytokines and acute-phase proteins. If inflammation can, in turn, increase adipose tissue growth, this may be the basis for a positive feedback loop in obesity. We have developed a tissue engineering model for growing adipose tissue in the mouse that allows quantification of increases in adipogenesis. In this study, we evaluated the adipogenic potential of the inflammogens monocyte chemoattractant protein (MCP)-1 and zymosan-A (Zy) in a murine tissue engineering model.Research Methods and Procedures: MCP-1 and Zy were added to chambers filled with Matrigel and fibroblast growth factor 2. To analyze the role of inducible nitric oxide synthase (iNOS), the iNOS inhibitor aminoguanidine was added to the chamber.Results: Our results show that MCP-1 generated proportionally large quantities of new adipose tissue. This neoadipogenesis was accompanied by an ingrowth of macrophages and could be mimicked by Zy. Aminoguanidine significantly inhibited the formation of adipose tissue.Discussion: Our findings demonstrate that low-grade inflammation and iNOS expression are important factors in adipogenesis. Because fat neoformation in obesity and the metabolic syndrome is believed to be mediated by macrophage-derived proinflammatory cytokines, this adipose tissue engineering system provides a model that could potentially be used to further unravel the pathogenesis of these two metabolic disorders.