Increased inflammatory properties of adipose tissue macrophages recruited during diet-induced obesity
Increased inflammatory properties of adipose tissue macrophages recruited during diet-induced obesity
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DOI：
10.2337/db06-1076
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发表时间：
2007-01-01
期刊：
影响因子：
7.7
通讯作者：
Saltiel, Alan R.
中科院分区：
文献类型：
--
作者：
Lumeng, Carey N.;DeYoung, Stephanie M.;Saltiel, Alan R.
尽管近期研究表明，脂肪组织巨噬细胞（ATMs）参与肥胖中的炎症变化并导致胰岛素抵抗，但这些细胞的特性尚未得到充分了解。我们假设，在高脂饮食期间被招募到脂肪组织的ATMs与驻留组织的ATMs相比，具有独特的炎症特性。我们利用一种染料（PKH26）在体内对ATMs进行脉冲标记，纯化了在高脂饮食期间被招募到白色脂肪组织的巨噬细胞。通过实时逆转录聚合酶链反应（RT - PCR）和互补脱氧核糖核酸（cDNA）微阵列对被招募的和驻留的ATMs的基因表达进行比较，结果显示被招募的ATMs过度表达在巨噬细胞迁移和吞噬作用中起重要作用的基因，包括白细胞介素 - 6（IL - 6）、诱导型一氧化氮合酶（NOS）和C - C趋化因子受体2（CCR2）。在高脂饮食喂养的CCR2基因敲除小鼠的ATMs中，许多这些基因未被诱导，这支持了CCR2在调节肥胖期间炎症性ATMs招募中的重要性。此外，载脂蛋白E（Apoe）的表达降低，而在脂质代谢中起重要作用的基因，如过氧化物酶体增殖物激活受体γ（Pparg）、脂肪细胞脂肪酸结合蛋白（Aft）、硬脂酰辅酶A去饱和酶1（Srepf1）和载脂蛋白B - 48受体（Apob48r）在被招募的巨噬细胞中表达增加。与此相符的是，与瘦小鼠相比，肥胖小鼠的ATMs脂质含量增加。这些研究表明，肥胖动物中被招募的ATMs代表了一类具有独特特性的巨噬细胞亚群。
Although recent studies show that adipose tissue macrophages (ATMs) participate in the inflammatory changes in obesity and contribute to insulin resistance, the properties of these cells are not well understood. We hypothesized that ATMs recruited to adipose tissue during a high-fat diet have unique inflammatory properties compared with resident tissue ATMs. Using a dye (PKH26) to pulse label ATMs in vivo, we purified macrophages recruited to white adipose tissue during a high-fat diet. Comparison of gene expression in recruited and resident ATMs using real-time RT-PCR and cDNA microarrays showed that recruited ATMs overexpress genes important in macrophage migration and phagocytosis, including interleukin-6 (IL-6), inducible nitric oxide synthase (NOS), and C-C chemokine receptor 2 (CCR2). Many of these genes were not induced in ATMs from high-fat diet-fed CCR2 knockout mice, supporting the importance of CCR2 in regulating recruitment of inflammatory ATMs during obesity. Additionally, expression of Apoe was decreased, whereas genes important in lipid metabolism, such as Pparg, Aft, Srepf1, and Apob48r, were increased in the recruited macrophages. In agreement with this, ATMs from obese mice had increased lipid content compared with those from lean mice. These studies demonstrate that recruited ATMs in obese animals represent a subclass of macrophages with unique properties.