Receptor for advanced glycation end-products (RAGE) regulation of adiposity and adiponectin is associated with atherogenesis in apoE-deficient mouse
Receptor for advanced glycation end-products (RAGE) regulation of adiposity and adiponectin is associated with atherogenesis in apoE-deficient mouse
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DOI：
10.1016/j.atherosclerosis.2010.04.006
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发表时间：
2010-08-01
期刊：
影响因子：
5.3
通讯作者：
Nishizawa, Yoshiki
中科院分区：
文献类型：
--
作者：
Ueno, Hiroki;Koyama, Hidenori;Nishizawa, Yoshiki
目的：晚期糖基化终产物受体（RAGE）已被证实与心血管疾病有关。我们研究了RAGE在非糖尿病状态下参与动脉粥样硬化及其与肥胖影响的关系。方法：将载脂蛋白E(apoE)(-/-) RAGE（+/+）或载脂蛋白E(-/-) RAGE（-/-）小鼠分别饲喂致动脉粥样硬化饮食或标准饲料。用附睾脂肪组织重量、脂肪细胞大小、血清脂联素测定肥胖程度。以形态计量学方法测定主动脉粥样硬化。结果：ApoE(-/-) RAGE（-/-）小鼠的主动脉斑块总面积明显小于ApoE(-/-) RAGE（+/+）小鼠。apoE(-/-) RAGE（-/-）小鼠的体重、附睾脂肪重量和附睾脂肪细胞大小也显著小于apoE(-/-) RAGE（+/+）小鼠。apoE(-/-) RAGE（-/-）小鼠血清脂联素显著高于apoE(-/-) RAGE（+/+）小鼠，而非肿瘤坏死因子- α。简单回归分析显示，主动脉斑块总面积与附睾脂肪重量、附睾脂肪细胞大小呈正相关，与血清脂联素水平呈负相关。多元回归分析显示，RAGE基因型与血清脂联素在主动脉粥样硬化中相互关联。最后，免疫组织化学和实时RT-PCR分析显示，RAGE确实在附睾脂肪组织的脂肪细胞和内皮细胞中表达。结论：非糖尿病状态下rage介导的肥胖调节可能与动脉粥样硬化的进展有关。2010爱思唯尔爱尔兰有限公司版权所有。
Objective: Receptor for advanced glycation end-products (RAGE) has been shown to be involved in cardiovascular diseases. We examined the involvement of RAGE in atherosclerosis under non-diabetic status, and its relation to the effect on adiposity.Methods: Apolipoprotein E (apoE)(-/-) RAGE(+/+) or apoE(-/-) RAGE(-/-) mice were fed with an atherogenic diet or the standard chow diet. Adiposity was determined by weight of epididymal adipose tissue, adipocyte size and serum adiponectin. Aortic atherosclerosis was morphometrically determined.Results: ApoE(-/-) RAGE(-/-) mice exhibited significantly less total aortic plaque area than apoE(-/-) RAGE(+/+) mice. Body weight, epididymal fat weight, and epididymal adipocyte size were also significantly less in apoE(-/-) RAGE(-/-) mice than apoE(-/-) RAGE(+/+) mice. Serum adiponectin, but not tumor necrosis factor-alpha, was significantly higher in apoE(-/-) RAGE(-/-) mice than apoE(-/-) RAGE(+/+) mice. Simple regression analysis revealed that the total aortic plaque area was positively associated with epididymal fat weight, epididymal adipocyte size, and negatively with serum adiponectin levels. Multiple regression analyses revealed that RAGE genotype and serum adiponectin were mutually interrelated in determining aortic atherosclerosis. Finally, immunohistochemical and real-time RT-PCR analyses revealed that RAGE was indeed expressed in both adipocytes and endothelial cells in epididymal adipose tissue.Conclusion: RAGE-mediated regulation of adiposity in non-diabetic status could be attributable to the progression of atherosclerosis. (C) 2010 Elsevier Ireland Ltd. All rights reserved.