Adipose tissue macrophages in insulin resistant subjects are 1 associated with collagen VI, fibrosis and demonstrate 2 alternative activation
Adipose tissue macrophages in insulin resistant subjects are 1 associated with collagen VI, fibrosis and demonstrate 2 alternative activation
复制标题
DOI：
--
复制
发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Michael Spencer;A. Yao-Borengasser;R. Unal;N. Rasouli;M. Catherine;Gurley;Beibei Zhu;C. Peterson;P. Kern
中科院分区：
文献类型：
--
作者：
Michael Spencer;A. Yao-Borengasser;R. Unal;N. Rasouli;M. Catherine;Gurley;Beibei Zhu;C. Peterson;P. Kern
脂肪组织巨噬细胞与胰岛素抵抗有关，并与细胞外基质（ECM）的39种变化有关。为了更好地表征脂肪40巨噬细胞、ECM和脂肪细胞-巨噬细胞相互作用，针对炎症42和纤维化的标志物评估来自脂肪组织和基质血管部分的基因表达，并且对来自肥胖和瘦受试者的巨噬细胞进行计数并进行化学表征。共培养实验检测了44种脂肪细胞-巨噬细胞相互作用的影响。胶原VI基因表达与45种胰岛素敏感性（SI）和CD 68（r=-0.56和r=0.60，p<0.0001）以及与其他46种炎症和纤维化标志物相关。当与瘦型相比时，肥胖脂肪组织47含有增加的纤维化面积，其与胰岛素敏感性48（r=-0.58，p<0.02）负相关，与巨噬细胞数量正相关（r=0.70，p<0.01）。虽然49个巨噬细胞在冠状结构（CLS）中更丰富的肥胖脂肪，50大多数的巨噬细胞与纤维化，并没有组织在CLS。CLS中的51个巨噬细胞主要是M1，但大多数其他巨噬细胞，特别是纤维化区域中的52个巨噬细胞，是M2，并且还表达M2 c 53巨噬细胞的标志物CD 150。THP 1巨噬细胞与脂肪细胞的共培养促进了M2 54表型，具有较低的IL 1和较高的IL 10：IL 12比率。TGF- β在55 M2巨噬细胞中更丰富，并且通过与脂肪细胞共培养进一步增加。在巨噬细胞和脂肪细胞中，TGF- β下游的56种效应物如派-1、胶原VI和p-Smad均增加。因此，胰岛素抵抗的人的脂肪组织表现出增加的纤维化、M2巨噬细胞丰度和TGF- β活性。
Adipose tissue macrophages are associated with insulin resistance and are linked with 39 changes in the extracellular matrix (ECM). To better characterize adipose 40 macrophages, the ECM, and adipocyte–macrophage interactions, gene expression from 41 adipose tissue and stromal vascular fraction was assessed for markers of inflammation 42 and fibrosis, and macrophages from obese and lean subjects were counted and 43 characterized immunohistochemically. Coculture experiments examined the effects of 44 adipocyte-macrophage interaction. Collagen VI gene expression was associated with 45 insulin sensitivity (S I ) and CD68 (r=-0.56, and r=0.60, p<0.0001), and with other 46 markers of inflammation and fibrosis. When compared to lean, obese adipose tissue 47 contained increased areas of fibrosis which correlated inversely with insulin sensitivity 48 (r=-0.58, p<0.02) and positively with macrophage number (r=0.70, p<0.01). Although 49 macrophages in crown-like structure (CLS) were more abundant in obese adipose, the 50 majority of macrophages were associated with fibrosis and were not organized in CLS. 51 Macrophages in CLS were predominantly M1, but most other macrophages, particularly 52 those in fibrotic areas, were M2, and also expressed CD150, a marker of M2c 53 macrophages. Coculture of THP1 macrophages with adipocytes promoted the M2 54 phenotype, with lower IL1, and a higher IL10:IL12 ratio. TGF- β was more abundant in 55 M2 macrophages and was further increased by coculture with adipocytes. Downstream 56 effectors of TGF- β such as PAI-1, collagen VI and p-Smad were increased in both macrophages and adipocytes. Thus, adipose tissue of insulin resistant humans demonstrated increased fibrosis, M2 macrophage abundance and TGF- β activity.