Obesity-associated glomerular inflammation increases albuminuria without renal histological changes.

Obesity-associated glomerular inflammation increases albuminuria without renal histological changes.
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DOI:
10.1002/2211-5463.12400
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发表时间:
2018-04
期刊:
影响因子:
2.6
通讯作者:
Ueshima S
Ueshima S
中科院分区:
生物学4区
文献类型:
--
作者:
Mima A;Yasuzawa T;King GL;Ueshima S

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肥胖是慢性肾脏病(CKD)的危险因素之一,但其确切机制尚不清楚。本研究描述了肥胖大鼠中肥胖诱导的肾小球炎症、氧化应激和白蛋白尿的影响。从脂肪(ZF)和瘦(ZL)Zucker大鼠收集肾小球样品。喂养2个月后,与ZL大鼠相比,ZF大鼠的体重和蛋白尿显著增加。ZF大鼠肾小球中炎症标志物TNF-α和CCR 2的表达显著增加。然而,IL-6 mRNA的表达没有增加。肾脏病理分析显示无肾小球扩张。由于炎症和氧化应激标志物与NF-κB相关,我们评估了高脂饮食小鼠肾小球中NF-κB活化是否增加。免疫组织化学显示,当用高脂饮食喂养过表达NF-κB依赖性增强型绿色荧光蛋白的转基因小鼠时,肾小球中NF-κB活化增加。这些结果表明,仅持续2个月的肥胖可引起蛋白尿,这是由于炎症或氧化应激增加,但可能不足以长时间发展为肾脏病理变化。
Obesity is one of risk factors for chronic kidney disease (CKD), but the precise mechanism involved is unclear. This study characterizes the effect of obesity‐induced glomerular inflammation, oxidative stress, and albuminuria in obese rats. Glomerular samples were collected from fatty (ZF) and lean (ZL) Zucker rats. After 2 months of feeding, body weight and albuminuria were significantly increased in ZF rats when compared to ZL rats. Expression of the inflammatory markers TNF‐α and CCR2 was significantly increased in the glomeruli of ZF rats. However, expression of IL‐6 mRNA was not increased. Analysis of renal pathology showed no glomerular expansion. As inflammatory and oxidative stress markers are associated with NF‐κB, we evaluated whether NF‐κB activation was increased in the glomeruli of mice on a high‐fat diet. Immunohistochemistry showed increased NF‐κB activation in the glomeruli when transgenic mice overexpressing an NF‐κB‐dependent enhanced green fluorescent protein were fed with a high‐fat diet. These results suggest that obesity of only 2 months duration can cause albuminuria, due to increased inflammation or oxidative stress, but may not be long enough to develop renal pathological changes.
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