NOX activity in brain aging: exacerbation by high fat diet.

NOX activity in brain aging: exacerbation by high fat diet.
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DOI:
10.1016/j.freeradbiomed.2010.03.006
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发表时间:
2010-07-01
影响因子:
7.4
通讯作者:
Keller, Jeffrey N.
Keller, Jeffrey N.
中科院分区:
医学1区
文献类型:
--
作者:
Bruce-Keller, Annadora J.;White, Christy L.;Gupta, Sunita;Knight, Alecia G.;Pistell, Paul J.;Ingram, Donald K.;Morrison, Christopher D.;Keller, Jeffrey N.

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这项研究描述了年龄和高脂肪饮食如何影响 NADPH 氧化酶 (NOX) 的特征。具体而言,在暴露于西方饮食(WD,41% 卡路里来自脂肪)或极高脂肪猪油饮食(VHFD,60% 卡路里来自脂肪)4 个月后,对 7、16 和 24 个月大的小鼠的额叶大脑皮层中的 NOX 活性和亚基表达进行了评估。数据揭示了年龄对 NOX 活性的显着影响,并且表明 NOX 活性仅通过 VHFD 增加,并且仅在 24 个月大的小鼠中。仅在老年小鼠中,饮食也会增加 NOX 亚基的表达。蛋白质羰基的定量揭示了与年龄相关的蛋白质氧化的显着增加,并表明只有老年小鼠对高脂肪饮食的反应会增强蛋白质氧化。组织学分析表明 NOX 亚基和蛋白质羰基化的神经元定位显着。最后,数据表明,反应性小胶质细胞增生的变化(而非星形细胞增多)反映了饮食诱导的 NOX 活化和蛋白质氧化的模式。总的来说,这些数据表明年龄和膳食脂肪都会驱动 NOX 激活,并进一步表明老年小鼠对高脂肪饮食的影响优先敏感。这些数据还表明,高脂肪饮食可能会通过增加氮氧化物而加剧大脑中与年龄相关的氧化应激。
This study describes how age and high fat diet affect the profile of NADPH oxidase (NOX). Specifically, NOX activity and subunit expression were evaluated in the frontal cerebral cortex of 7-, 16-, and 24-month old mice following a 4-month exposure to either Western diet (WD, 41% calories from fat) or very high fat lard diet (VHFD, 60% calories from fat). Data reveal a significant effect of age in on NOX activity, and show that NOX activity was only increased by VHFD, and only in 24-month old mice. NOX subunit expression was also increased by diet only in older mice. Quantification of protein carbonyls revealed significant age-related increases in protein oxidation, and indicate that only aged mice respond to high fat diet with enhanced protein oxidation. Histological analyses indicate prominent neuronal localization of both NOX subunits and protein carbonylation. Finally, data indicate that changes in reactive microgliosis, but not astrocytosis, mirror the pattern of diet-induced NOX activation and protein oxidation. Collectively, these data show that both age and dietary fat drive NOX activation, and further indicate that aged mice are preferentially sensitive to the effects of high fat diet. These data also suggest that high fat diets might exacerbate age-related oxidative stress in the brain via increased NOX.
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DOI: 10.1016/j.bbadis.2008.10.004
发表时间: 2009-05
影响因子: 6.2
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