Adverse Effects of Excessive Leucine Intake Depend on Dietary Protein Intake: A Transcriptomic Analysis to Identify Useful Biomarkers
Adverse Effects of Excessive Leucine Intake Depend on Dietary Protein Intake: A Transcriptomic Analysis to Identify Useful Biomarkers
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DOI：
10.3177/jnsv.59.45
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发表时间：
2013-02-01
影响因子：
1.6
通讯作者：
Kato, Hisanori
中科院分区：
文献类型：
--
作者：
Imamura, Wataru;Yoshimura, Ryoji;Kato, Hisanori
本研究旨在通过基因芯片技术筛选过量亮氨酸（Leu）对SD大鼠毒性作用的可靠基因标志物。长期以来，人们都知道过量氨基酸摄入的不良影响取决于膳食蛋白质水平。雄性大鼠分为12组（n = 6），分别饲喂低蛋白（6%）、中蛋白（12%）和高蛋白（40%）饲料1周。在日粮中添加不同水平的亮氨酸（0，2，4和8%）。在6%蛋白质中含有超过4% Leu的饮食消费导致生长迟缓和肝脏重量减少，而给予相同剂量的Leu与12%或40%蛋白质并没有影响它们。通过系统的数据提取过程，确定了6个候选基因标记。从低蛋白饮食中含有0、2、3、4和8%Leu的另一个实验中获得的肝脏基因表达数据用于通过受试者操作特征（ROC）曲线分析来检查这些生物标志物候选物的有效性。所有候选生物标记物的AUC值均大于0.700，表明候选标记物作为Leu过量指标的有效性。通过基因标记物的多元回归分析获得的基因标记物组的ROC曲线的截止值表明，高于3%的Leu水平具有不利影响。总之，基因标记物小组表明，对于雄性大鼠，2%的饮食Leu补充剂是低蛋白（6%）饮食中的NOAEL剂量。
The present study was conducted to identify reliable gene biomarkers for the adverse effects of excessive leucine (Leu) in Sprague-Dawley rats by DNA microarray. It has long been known that the adverse effects of excessive amino acid intake depend on dietary protein levels. Male rats were divided into 12 groups (n = 6) and fed for 1 wk a diet containing low (6%), moderate (12%) or high (40%) protein. Different levels of Leu (0, 2, 4, and 8%) were added to the diets. Consumption of diets containing more than 4% Leu in 6% protein resulted in growth retardation and reduced liver weight, whereas the administration of the same dose of Leu with 12% or 40% protein did not affect them. By a process of systematic data extraction, 6 candidate gene markers were identified. The liver gene expression data obtained from another experiment with 0, 2, 3, 4, and 8% Leu in a low-protein diet was used to examine the validity of these biomarker candidates with receiver operating characteristic (ROC) curve analysis. All of AUC values of the biomarker candidates were more than 0.700, suggesting the effectiveness of the marker candidates as the indices of Leu excess. The cut-off value for the ROC curve of the gene-marker panel, which was obtained by multiple regression analysis of gene markers, indicated that Leu levels higher than 3% have adverse effects. In conclusion, the gene-marker panel suggested that for male rats dietary Leu supplementation of 2% is the NOAEL dose in low-protein (6%) diets.