Eder Klaus, Siebers Marina, Most Erika, Scheibe Susan, Weissmann Norbert, Gessner Denise K
Institute of Animal Nutrition and Nutrition Physiology, Justus-Liebig-Universität Gießen, Heinrich-Buff-Ring 26-32, 35392 Gießen, Germany.
Excellence Cluster Cardio-Pulmonary System (ECCPS), Justus-Liebig-Universität Gießen, Aulweg 130, 35392 Gießen, Germany.
Nutr Metab (Lond). 2017 Nov 16;14:71. doi: 10.1186/s12986-017-0225-z. eCollection 2017.
Reactive oxygen species (ROS) are known to stimulate the activation of nuclear factor-erythroid 2-related factor-2 (Nrf2), the key regulator of the antioxidant and cytoprotective defense system in the body. The hypothesis underlying this study was that high dietary concentrations of vitamin E suppress Nrf2 activation, and thus could weaken the body's antioxidative and cytoprotective capacity. As the effect of vitamin E on Nrf2 pathway might be influenced by concentrations of fatty acids susceptible to oxidation in the diet, we used also diets containing either soybean oil as a reference oil or salmon oil as a source of oil rich in n-3 polyunsatuated fatty acids.
Seventy-two rats were divided into 6 groups of rats which received diets with either 25, 250 or 2500 mg vitamin E/kg, with either soybean oil or salmon oil as dietary fat sources according to a bi-factorial experimental design. Electron spin resonance spectroscopy was used to determine ROS production in the liver. qPCR analysis and western blot were performed to examine the expression of Nrf2 target genes in the liver of rats.
Rats fed the salmon oil diet with 25 mg vitamin E/kg showed a higher production of ROS in the liver than the 5 other groups of rats which did not differ in ROS production. Relative mRNA concentrations of (encoding Nrf2), and various Nrf2 target genes, protein concentrations of glutathione peroxidase (GPX), heme oxygenase 1 (HO-1), NAD(P)H quinone dehydrogenase 1 (NQO1) and activities of the antioxidant enzymes GPX, superoxide dismutase and catalase were not influenced by the dietary vitamin E concentration. The dietary fat had also less effect on Nrf2 target genes and no effect on protein concentrations of GPX, HO-1, NQO1 and activities of antioxidant enzymes. Dietary vitamin E concentration and type of fat moreover had less effect on mRNA concentrations of genes and concentrations of proteins involved in the unfolded protein response, a pathway which is closely linked with activation of Nrf2.
We conclude that excess dietary concentrations of vitamin E do not suppress Nrf2 signaling, and thus do not weaken the endogenous antioxidant and cytoprotective capacity in the liver of rats.
已知活性氧（ROS）可刺激核因子红细胞2相关因子2（Nrf2）的激活，Nrf2是体内抗氧化和细胞保护防御系统的关键调节因子。本研究的假设是，高膳食浓度的维生素E会抑制Nrf2的激活，从而可能削弱机体的抗氧化和细胞保护能力。由于维生素E对Nrf2途径的影响可能受饮食中易氧化脂肪酸浓度的影响，我们还使用了以大豆油作为参考油或鲑鱼油作为富含n-3多不饱和脂肪酸的油源的饮食。
根据双因素实验设计，将72只大鼠分为6组，分别给予每千克含25、250或2500毫克维生素E的饮食，饮食脂肪来源分别为大豆油或鲑鱼油。采用电子自旋共振光谱法测定肝脏中的ROS产生。进行qPCR分析和蛋白质印迹法检测大鼠肝脏中Nrf2靶基因的表达。
饲喂每千克含25毫克维生素E的鲑鱼油饮食的大鼠肝脏中ROS产生量高于其他5组大鼠，其他5组大鼠的ROS产生量无差异。（编码Nrf2）、 及各种Nrf2靶基因的相对mRNA浓度、谷胱甘肽过氧化物酶（GPX）、血红素加氧酶1（HO-1）、NAD（P）H醌脱氢酶1（NQO1）的蛋白质浓度以及抗氧化酶GPX、超氧化物歧化酶和过氧化氢酶的活性不受膳食维生素E浓度的影响。膳食脂肪对Nrf2靶基因的影响也较小，对GPX、HO-1、NQO1的蛋白质浓度和抗氧化酶活性无影响。此外，膳食维生素E浓度和脂肪类型对与未折叠蛋白反应相关的基因mRNA浓度和蛋白质浓度的影响较小，未折叠蛋白反应是一条与Nrf2激活密切相关的途径。
我们得出结论，膳食中过量的维生素E不会抑制Nrf2信号传导，因此不会削弱大鼠肝脏中的内源性抗氧化和细胞保护能力。
