From the Cover: Zinc Deficiency Worsens and Supplementation Prevents High-Fat Diet Induced Vascular Inflammation, Oxidative Stress, and Pathological Remodeling
From the Cover: Zinc Deficiency Worsens and Supplementation Prevents High-Fat Diet Induced Vascular Inflammation, Oxidative Stress, and Pathological Remodeling
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封面文章：缺锌会恶化，补充锌可以预防高脂肪饮食引起的血管炎症、氧化应激和病理重塑。
DOI：
10.1093/toxsci/kfw110
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发表时间：
2016-09-01
影响因子：
3.8
通讯作者：
Tan, Yi
中科院分区：
文献类型：
--
作者：
Chen, Jun;Wang, Shudong;Tan, Yi
肥胖已成为世界上常见的公共卫生问题，并增加了各种心血管疾病的风险。锌对多个器官的正常结构和功能是必不可少的。本研究观察了高脂饮食(HFD)诱导的肥胖对小鼠主动脉的影响，并评价了锌缺乏或补充对其的影响。4周龄雄性C57BL/6J小鼠饲喂不同锌水平的高脂饲料(缺锌、补锌和适量补锌)3个月和6个月。结果显示，高脂饲料喂养诱导了时间依赖性的主动脉重构，表现为血管壁厚度增加，膜细胞增殖和纤维化反应，以及炎症反应，反映为炎性细胞因子(肿瘤坏死因子-α和血管细胞黏附分子1)的表达增加。高脂饲料还引起主动脉氧化损伤，表现为3-硝基酪氨酸和4-羟基-2-壬烯醛蓄积，下调核因子(红系2)样蛋白2(Nrf2)的表达和功能，表现为其下游抗氧化剂过氧化氢酶、NAD(P)H脱氢酶(苯醌1)和金属硫蛋白的表达下调。高脂饮食所致肥胖的血管效应在缺锌时加重，补锌后明显改善。此外，Nrf2功能的下调和相关抗氧化剂的表达也因缺锌而恶化，但经补锌后得到改善。这些结果表明，高脂饲料可引起主动脉重塑，缺锌可加重主动脉重塑，补锌可改善主动脉重塑。
Obesity has become a common public health problem in the world and raises the risk of various cardiovascular diseases. Zinc is essential for multiple organs in terms of normal structure and function. The present study investigated the effects of high fat diet (HFD) induced obesity on the aorta in mice, and evaluated whether it can be affected by zinc deficiency or supplementation. Four-week-old male C57BL/6J mice were fed HFD with varied amounts of zinc (deficiency, adequate and supplementation) for 3 and 6 months. Results showed that HFD feeding induced a time-dependent aortic remodeling, demonstrated by increased vessel wall thickness, tunica cell proliferation and fibrotic responses, and inflammatory response, reflected by increased expression of inflammatory cytokines (tumor necrosis factor-alpha and vascular cell adhesion molecule 1). HFD feeding also caused aortic oxidative damage, reflected by 3-nitrotyrosine and 4-hydroxy-2-nonenal accumulation, and down-regulated nuclear factor (erythroid-derived 2)-like 2 (Nrf2) expression and function, shown by down-regulation of its downstream antioxidants, catalase, NAD(P)H dehydrogenase (quinone 1), and metallothionein expression. The vascular effects of obesity-induced by HFD was exacerbated by zinc deficiency but significantly improved by zinc supplementation. In addition, down-regulation of Nrf2 function and associated antioxidants expression were also worsened by zinc deficiency but improved by zinc supplementation. These results suggest that HFD induces aortic remodeling, which can be exacerbated by zinc deficiency and improved by zinc supplementation.