Ambient air pollution exaggerates adipose inflammation and insulin resistance in a mouse model of diet-induced obesity.
Ambient air pollution exaggerates adipose inflammation and insulin resistance in a mouse model of diet-induced obesity.
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DOI：
10.1161/circulationaha.108.799015
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发表时间：
2009-02-03
期刊：
影响因子：
37.8
通讯作者：
Rajagopalan S
中科院分区：
文献类型：
--
作者：
Sun Q;Yue P;Deiuliis JA;Lumeng CN;Kampfrath T;Mikolaj MB;Cai Y;Ostrowski MC;Lu B;Parthasarathy S;Brook RD;Moffatt-Bruce SD;Chen LC;Rajagopalan S
城市化和2型糖尿病之间有很强的联系。虽然已经提出了多种机制，但没有研究评估环境空气污染物的影响和发展为2型糖尿病的倾向。我们假设暴露于环境细颗粒物（<2.5 μm; PM2.5）会加剧饮食诱导的胰岛素抵抗、脂肪炎症和内脏肥胖。雄性C57BL/6小鼠喂食高脂肪食物10周，随机分配到高浓度环境PM2.5或过滤空气中（每组14只），持续24周。暴露于pm2.5的C57BL/6小鼠表现出明显的全身胰岛素抵抗、全身炎症和内脏脂肪增加。PM2.5暴露诱导胰岛素抵抗特征的信号异常，包括内皮细胞中Akt和内皮一氧化氮合酶磷酸化降低，蛋白激酶C表达增加。这些异常与血管对胰岛素和乙酰胆碱的松弛异常有关。PM2.5增加了内脏脂肪中脂肪组织巨噬细胞（F4/80+细胞）表达较高水平的肿瘤坏死因子-α/白细胞介素-6和较低水平的白细胞介素-10/ n-乙酰半乳糖胺特异性凝集素1。为了测试PM2.5对诱导单核细胞直接浸润脂肪的影响，我们将表达黄色荧光蛋白（YFP）的FVBN小鼠置于单核细胞特异性启动子（c-fms, c-fmsYFP）的糖尿病控制下10周，然后将这些小鼠暴露于PM2.5或气管内盐水中。PM2.5诱导YFP细胞在内脏脂肪中积累，增强YFP细胞在微循环中的粘附。PM2.5暴露会加重胰岛素抵抗和内脏炎症/肥胖。这些发现为空气污染和2型糖尿病之间提供了新的联系。
There is a strong link between urbanization and type 2 diabetes mellitus. Although a multitude of mechanisms have been proposed, there are no studies evaluating the impact of ambient air pollutants and the propensity to develop type 2 diabetes mellitus. We hypothesized that exposure to ambient fine particulate matter (<2.5 μm; PM2.5) exaggerates diet-induced insulin resistance, adipose inflammation, and visceral adiposity. Male C57BL/6 mice were fed high-fat chow for 10 weeks and randomly assigned to concentrated ambient PM2.5 or filtered air (n=14 per group) for 24 weeks. PM2.5-exposed C57BL/6 mice exhibited marked whole-body insulin resistance, systemic inflammation, and an increase in visceral adiposity. PM2.5 exposure induced signaling abnormalities characteristic of insulin resistance, including decreased Akt and endothelial nitric oxide synthase phosphorylation in the endothelium and increased protein kinase C expression. These abnormalilties were associated with abnormalities in vascular relaxation to insulin and acetylcholine. PM2.5 increased adipose tissue macrophages (F4/80+ cells) in visceral fat expressing higher levels of tumor necrosis factor-α/interleukin-6 and lower interleukin-10/N-acetyl-galactosamine specific lectin 1. To test the impact of PM2.5 in eliciting direct monocyte infiltration into fat, we rendered FVBN mice expressing yellow fluorescent protein (YFP) under control of a monocyte-specific promoter (c-fms, c-fmsYFP) diabetic over 10 weeks and then exposed these mice to PM2.5 or saline intratracheally. PM2.5 induced YFP cell accumulation in visceral fat and potentiated YFP cell adhesion in the microcirculation. PM2.5 exposure exaggerates insulin resistance and visceral inflammation/adiposity. These findings provide a new link between air pollution and type 2 diabetes mellitus.