NOX2 deficiency attenuates markers of adiposopathy and brain injury induced by high-fat diet
NOX2 deficiency attenuates markers of adiposopathy and brain injury induced by high-fat diet
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DOI：
10.1152/ajpendo.00398.2012
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发表时间：
2013-02-01
影响因子：
5.1
通讯作者：
Bruce-Keller, Annadora J.
中科院分区：
文献类型：
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作者：
Pepping, Jennifer K.;Freeman, Linnea R.;Bruce-Keller, Annadora J.
Pepping JK, Freeman LR, Gupta S, Keller JN, Bruce-Keller AJ。NOX2缺乏可减弱高脂饮食引起的脂肪病和脑损伤标志物。[J] .中国生物医学工程学报，2016,31(4):394 - 394。2012年12月11日首次发表；doi: 10.1152 / ajpendo.00398.2012。在现代社会中，高脂肪/高热量饮食的消费可能是肥胖流行的主要原因，肥胖会增加癌症、心血管疾病和神经损伤的患病率。肥胖可能通过炎症和氧化信号导致衰退，而将炎症与氧化应激联系起来的一个因素是促炎、促氧化酶NADPH氧化酶。为了揭示NADPH氧化酶在肥胖的代谢和神经系统后果中的作用，我们比较了高脂肪饮食对野生型C57B1/6 （WT）小鼠和缺乏NAPDH氧化酶亚基NOX2 （NOX2KO）小鼠的影响。虽然WT和NOX2KO小鼠的饮食诱导体重增加相似，但NOX2KO小鼠的内脏脂肪沉积较小，内脏脂肪细胞肥大减轻，内脏脂肪巨噬细胞浸润减少。此外，HFD对NOX2KO小鼠脂肪细胞功能和损伤标志物的有害影响减弱；NOX2KO小鼠改善了葡萄糖调节，对NOX2表达的评估发现巨噬细胞是内脏脂肪中NOX2阳性细胞的主要群体。最后，使用脑血管完整性、突触密度和反应性胶质瘤标记物评估脑损伤，数据显示高脂肪饮食破坏了WT小鼠的标记物表达，而NOX2KO小鼠没有。综上所述，这些数据表明NOX2是高脂肪饮食致病作用的重要因素，并强化了内脏脂肪炎症在代谢和神经功能衰退中的关键作用。基于noxx的治疗方法的开发可以在代谢综合征的背景下相应地保护代谢和神经功能。
Pepping JK, Freeman LR, Gupta S, Keller JN, Bruce-Keller AJ. NOX2 deficiency attenuates markers of adiposopathy and brain injury induced by high-fat diet. Am J Physiol Endocrinol Metab 304: E392-E404, 2013. First published December 11, 2012; doi:10.1152/ajpendo.00398.2012.-The consumption of high-fat/calorie diets in modern societies is likely a major contributor to the obesity epidemic, which can increase the prevalence of cancer, cardiovascular disease, and neurological impairment. Obesity may precipitate decline via inflammatory and oxidative signaling, and one factor linking inflammation to oxidative stress is the proinflammatory, pro-oxidant enzyme NADPH oxidase. To reveal the role of NADPH oxidase in the metabolic and neurological consequences of obesity, the effects of high-fat diet were compared in wild-type C57B1/6 (WT) mice and in mice deficient in the NAPDH oxidase subunit NOX2 (NOX2KO). While diet-induced weight gains in WT and NOX2KO mice were similar, NOX2KO mice had smaller visceral adipose deposits, attenuated visceral adipocyte hypertrophy, and diminished visceral adipose macrophage infiltration. Moreover, the detrimental effects of HFD on markers of adipocyte function and injury were attenuated in NOX2KO mice; NOX2KO mice had improved glucose regulation, and evaluation of NOX2 expression identified macrophages as the primary population of NOX2-positive cells in visceral adipose. Finally, brain injury was assessed using markers of cerebrovascular integrity, synaptic density, and reactive gliosis, and data show that high-fat diet disrupted marker expression in WT but not NOX2KO mice. Collectively, these data indicate that NOX2 is a significant contributor to the pathogenic effects of high-fat diet and reinforce a key role for visceral adipose inflammation in metabolic and neurological decline. Development of NOX-based therapies could accordingly preserve metabolic and neurological function in the context of metabolic syndrome.