已知暴露于交通来源的空气污染会导致炎症性疾病的病因,包括心血管疾病(CVD)和肥胖;然而,所涉及的信号通路仍在调查中。肾素-血管紧张素系统(RAS)的失调可导致CVD并改变脂肪组织中的脂质储存和炎症。我们之前的暴露研究表明,交通产生的排放增加了RAS信号,高脂肪饮食进一步加剧了。因此,我们调查了暴露于发动机排放会增加全身和局部脂肪细胞RAS信号的假设,促进心血管疾病和肥胖相关因子的表达。雄性C57BL/6小鼠(6-8周龄)喂食高脂肪(HF,n=16)或低脂肪(LF,n=16)饮食,在曝光前30d开始,然后通过吸入暴露于任一过滤空气(FA,控制)或柴油发动机+汽油发动机车辆排放的混合物(MVE:100μgPM/m3)通过全身吸入6h/d,7天/周,30d.通过免疫荧光和RT-qPCR评估终点。MVE暴露促进血管粘附因子(VCAM-1,ICAM-1)表达,单核细胞/巨噬细胞隔离,和血管中的氧化应激,与血管紧张素II受体1型(AT1)表达增加有关。在肾脏,MVE暴露促进肾素的表达,AT1和AT2受体。在脂肪组织中,HF饮食和MVE暴露均介导附睾脂肪垫重量增加和脂肪细胞肥大,与血管紧张素原和AT1受体表达增加相关;然而,这些结局在MVE+HF组中进一步恶化.MVE暴露也会引起炎症,单核细胞趋化蛋白(MCP)-1和瘦素,同时减少胰岛素受体和葡萄糖转运蛋白,GLUT4,在脂肪组织中表达。我们的结果表明,MVE暴露促进全身和局部脂肪RAS信号,与CVD和肥胖相关的因子表达增加,HF饮食消耗进一步加剧。
Exposure to air pollution from traffic-generated sources is known to contribute to the etiology of inflammatory diseases, including cardiovascular disease (CVD) and obesity; however, the signaling pathways involved are still under investigation. Dysregulation of the renin-angiotensin system (RAS) can contribute to CVD and alter lipid storage and inflammation in adipose tissue. Our previous exposure studies revealed that traffic-generated emissions increase RAS signaling, further exacerbated by a high-fat diet. Thus, we investigated the hypothesis that exposure to engine emissions increases systemic and local adipocyte RAS signaling, promoting the expression of factors involved in CVD and obesity. Male C57BL/6 mice (6-8 wk old) were fed either a high-fat (HF, n = 16) or low-fat (LF, n = 16) diet, beginning 30d prior to exposures, and then exposed via inhalation to either filtered air (FA, controls) or a mixture of diesel engine + gasoline engine vehicle emissions (MVE: 100 μg PM/m3) via whole-body inhalation for 6 h/d, 7 d/wk, 30d. Endpoints were assessed via immunofluorescence and RT-qPCR. MVE-exposure promoted vascular adhesion factors (VCAM-1, ICAM-1) expression, monocyte/macrophage sequestration, and oxidative stress in the vasculature, associated with increased angiotensin II receptor type 1 (AT1) expression. In the kidney, MVE-exposure promoted the expression of renin, AT1, and AT2 receptors. In adipose tissue, both HF-diet and MVE-exposure mediated increased epididymal fat pad weight and adipocyte hypertrophy, associated with increased angiotensinogen and AT1 receptor expression; however, these outcomes were further exacerbated in the MVE + HF group. MVE-exposure also induced inflammation, monocyte chemoattractant protein (MCP)-1, and leptin, while reducing insulin receptor and glucose transporter, GLUT4, expression in adipose tissue. Our results indicate that MVE-exposure promotes systemic and local adipose RAS signaling, associated with increased expression of factors contributing to CVD and obesity, further exacerbated by HF diet consumption.