Macrophage-secreted factors inhibit ZAG expression and secretion by human adipocytes
Macrophage-secreted factors inhibit ZAG expression and secretion by human adipocytes
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DOI：
10.1016/j.mce.2010.05.020
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发表时间：
2010-08-30
影响因子：
4.1
通讯作者：
Bing, C.
中科院分区：
文献类型：
--
作者：
Gao, D.;Trayhurn, P.;Bing, C.
锌-α 2-糖蛋白（ZAG）是一种新的脂肪因子，在肥胖症的脂肪组织中下调，这种状态的特征是脂肪组织巨噬细胞浸润增加和慢性低度炎症。本研究调查了巨噬细胞分泌的因子和TNF-α（巨噬细胞的主要产物）是否调节人脂肪细胞的ZAG表达和分泌。ZAG主要由脂肪细胞产生，而不是由前脂肪细胞和巨噬细胞产生。将前脂肪细胞与巨噬细胞条件培养基孵育12天可降低ZAG mRNA和蛋白质的释放，以及脂肪形成标志物（PPAR γ和C/EBP α）的表达。用巨噬细胞条件培养基处理24 h的脂肪细胞显示ZAG mRNA和释放显著减少。慢性TNF-α治疗使脂肪细胞中ZAG表达和分泌显著降低，但促炎细胞因子和趋化因子（IL-6、瘦素、IL-8、MCP-1和RANTES）显著上调。这些发现表明，巨噬细胞相关炎症可能在肥胖症脂肪组织中ZAG的下调中起重要作用。(C)2010爱思唯尔爱尔兰有限公司版权所有。
Zinc-alpha 2-glycoprotein (ZAG), a novel adipokine, is downregulated in adipose tissue in obesity, a state characterized by increased adipose tissue macrophage infiltration and chronic low-grade inflammation. This study investigated whether macrophage-secreted factors and TNF-alpha, a major product of macrophages, modulate ZAG expression and secretion by human adipocytes. ZAG was produced primarily by adipocytes, and not by preadipocytes and macrophages. Incubation of preadipocytes with macrophage-conditioned medium for up to 12 days decreased ZAG mRNA and protein release, and the expression of adipogenic markers (PPAR gamma and C/EBP alpha). Adipocytes treated with macrophage-conditioned medium for 24 h displayed significant reductions in ZAG mRNA and release. Chronic TNF-alpha treatment let to significant decreases in ZAG expression and secretion, but marked upregulation of pro-inflammatory cytokines and chemokines (IL-6, leptin, IL-8, MCP-1 and RANTES) in adipocytes. These findings suggest that macrophage-associated inflammation may play a significant role in the downregulation of ZAG in adipose tissue in obesity. (C) 2010 Elsevier Ireland Ltd. All rights reserved.