Lipoic acid attenuates high-fat-diet-induced oxidative stress and B-cell-related immune depression
Lipoic acid attenuates high-fat-diet-induced oxidative stress and B-cell-related immune depression
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DOI：
10.1016/j.nut.2011.10.016
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发表时间：
2012-03-01
期刊：
影响因子：
4.4
通讯作者：
Le, Guo-Wei
中科院分区：
文献类型：
--
作者：
Cui, Jue;Xiao, Ying;Le, Guo-Wei
目的：研究高脂饮食(HFD)诱导的脾氧化应激是否影响B细胞活化相关基因的表达，从而导致B细胞相关免疫抑制。对照组食用普通饲料(4.9%脂肪，w/w)。另两组分别饲喂高脂饲料(21.2%脂肪)和高脂饲料+0.1%硫辛酸(LA)。10wk后检测血浆和脾组织氧化应激生物标志物超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶、总抗氧化能力、还原型谷胱甘肽/氧化谷胱甘肽比值、丙二醛含量。通过检测B细胞数量评价B细胞相关免疫功能，并用流式细胞仪检测脾淋巴细胞凋亡率。结果：HFD可诱导小鼠B细胞数量显著减少，脾淋巴细胞凋亡率显著增加，同时伴有氧化应激和氧化损伤增加。此外，互补DNA阵列分析结果显示，HFD诱导了与抗氧化防御相关的基因如超氧化物歧化酶-3(1.5倍)、金属硫蛋白-1(3.03倍)、谷胱甘肽过氧化物酶-5(17.15倍)和过氧化还蛋白-4(1.5)的表达下降，以及B细胞的激活，如免疫球蛋白重链6(2.46倍)、免疫球蛋白kappa链(1.74倍)、Fc受体(1.41倍)和RAS相关的C3肉毒杆菌底物1(7.46)。结论：LA可作为HFD的有效补充，通过增加B细胞受体信号通路的基因表达，预防氧化应激的发生，减轻B细胞损伤。(C)2012 Elsevier Inc.保留所有权利。
Objective: This study investigated whether spleen oxidative stress induced by a high-fat diet (HFD) influences the expression of genes involved in B-cell activation, thus leading to B-cell-related immunosuppression.Methods: Male C57BL/6 mice were randomly assigned to one of three groups with eight mice in each group. The control group consumed an ordinary diet (4.9% fat, w/w). The other two groups were fed an HFD (21.2% fat) and an HFD plus 0.1% lipoic acid (LA). After 10 wk, plasma and spleen oxidative stress biomarkers including superoxide dismutase, catalase, glutathione peroxidase, total antioxidant capacity, reduced glutathione/oxidized glutathione ratio, and malondialdehyde were examined. The B-cell-related immune function was evaluated by examining the number of B cells, and the apoptotic percentages of splenic lymphocytes were determined by flow cytometry. Furthermore, the B-cell activation and reactive oxygen species scavenger-related genes differentially expressed between mice fed an HFD and those fed an HFD supplemented with LA were identified through complementary DNA microarray.Results: The HFD induced marked decreases in the number of B cells and significantly increased the apoptotic percentages of splenic lymphocytes, accompanied by oxidative stress and increased oxidative damage, in the plasma and spleen. In addition, complementary DNA array analysis results showed that the HFD induced the decreased expression of genes associated with antioxidant defense, such as superoxide dismutase-3 (1.5-fold), metallothionein-1 (3.03-fold), glutathione peroxidase-5 (17.15-fold), and peroxiredoxin-4 (1.5), and B-cell activation, such as immunoglobulin heavy chain 6 (2.46-fold), immunoglobulin kappa-chain (1.74-fold), Fc receptor (1.41-fold), and RAS-related C3 botulinum substrate-1 (7.46). The LA supplement prevented the buildup of oxidative stress and upregulated related gene expressions.Conclusion: These results indicate a role for LA as a possible effective supplement with an HFD to prevent the development of oxidative stress and to attenuate B-cell damnification by increasing the gene expression of the B-cell receptor signaling pathway. (C) 2012 Elsevier Inc. All rights reserved.