PPAR γ is highly expressed in F4/80hi adipose tissue macrophages and dampens adipose-tissue inflammation
PPAR γ is highly expressed in F4/80hi adipose tissue macrophages and dampens adipose-tissue inflammation
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DOI：
10.1016/j.cellimm.2009.04.003
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发表时间：
2009-01-01
影响因子：
4.3
通讯作者：
Hontecillas, Raquel
中科院分区：
文献类型：
--
作者：
Bassaganya-Riera, Josep;Misyak, Sarah;Hontecillas, Raquel
巨噬细胞渗入脂肪组织是肥胖的标志。我们最近报道了脂肪组织巨噬细胞(ATM)的两个不同的表型亚群，基于糖蛋白F4/80的表面表达和对过氧化物酶体增殖物激活受体(PPAR)伽马激动剂治疗的反应性。因此，我们假设F4/80(Hi)和F4/80(Lo)ATM差异表达PPAR Gamma。本研究对肥胖患者的F4/80(Hi)和F4/80(Lo)ATM亚群进行了表型和功能特征分析。用实时定量RT-PCR方法检测分选的F4/80(L0)和F4/80(Hi)ATM上基因表达的变化。我们发现，虽然F4/80(LO)巨噬细胞在瘦小鼠的脂肪组织中占主导地位，但肥胖会导致F4/80(LO)和F4/80(Hi)ATM的积聚。此外，脂肪组织中F4/80(Hi)ATM的积聚与糖耐量受损有关。表型上，F4/80(Hi)ATM比F4/80(Lo)ATM表达更多的CD11c、MHC II、CD49b和CX3CR1，并产生更多的TNF-α、MCP-1和IL-10。基因表达分析表明，只有F4/80(Lo)群体产生IL-4，而F4/80(Hi)ATM群体表达更多的PPARγ、Delta、CD36和Toll样受体-4。此外，免疫细胞中PPAR-γ的缺乏有利于脂肪组织中M1的表达，并损害M2巨噬细胞标志物的表达。因此，PPARγ在F4/80(高)和F4/80(低)ATM亚群中差异表达，其缺陷有利于在WAT中以M1标记为主。(C)2009 Elsevier Inc.保留所有权利。
Macrophage infiltration into adipose tissue is a hallmark of obesity. We recently reported two phenotypically distinct subsets of adipose tissue macrophages (ATM) based on the surface expression of the glycoprotein F4/80 and responsiveness to treatment with a peroxisome proliferator-activated receptor (PPAR) gamma agonist. Hence, we hypothesized that F4/80(hi) and F4/80(lo) ATM differentially express PPAR gamma. This study phenotypically and functionally characterizes F4/80(hi) and F4/80(lo) ATM subsets during obesity. Changes in gene expression were also examined on sorted F4/80(lo) and F4/80(hi) ATM by quantitative real-time RT-PCR. We show that while F4/80(lo) macrophages predominate in adipose tissue of lean mice, obesity causes accumulation of both F4/80(lo) and F4/80(hi) ATM. Moreover, accumulation of F4/80(hi) ATM in adipose tissue is associated with impaired glucose tolerance. Phenotypically, F4/80(hi) ATM express greater amounts of CD11c, MHC II, CD49b, and CX3CR1 and produce more TNF-alpha, MCP-1, and IL-10 than F4/80(lo) ATM. Gene expression analyses of the sorted populations revealed that only the F4/80(lo) population produced IL-4, whereas the F4/80(hi) ATM expressed greater amounts of PPAR gamma, delta, CD36 and toll-like receptor-4. In addition, the deficiency of PPAR gamma in immune cells favors expression of M1 and impairs M2 macrophage marker expression in adipose tissue. Thus, PPAR gamma is differentially expressed in F4/80(hi) versus F4/80(low) ATM subsets and its deficiency favors a predominance of M1 markers in WAT. (C) 2009 Elsevier Inc. All rights reserved.