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首页> 外文期刊>Journal of Nutritional Science and Vitaminology >Adverse effects of excessive leucine intake depend on dietary protein intake: A transcriptomic analysis to identify useful biomarkers
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Adverse effects of excessive leucine intake depend on dietary protein intake: A transcriptomic analysis to identify useful biomarkers

机译:亮氨酸摄入过多的不良影响取决于饮食中蛋白质的摄入:通过转录组学分析来确定有用的生物标志物

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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.
机译:本研究旨在通过DNA芯片技术鉴定Sprague-Dawley大鼠中过量亮氨酸(Leu)的不良反应的可靠基因生物标记。早就知道过量摄入氨基酸的不良影响取决于饮食中的蛋白质水平。将雄性大鼠分成12组(n = 6),并以低蛋白(6%),中蛋白(12%)或高蛋白(40%)的饮食喂养1周。在饮食中添加了不同含量的Leu(0、2、4和8%)。日粮中所含的6%蛋白质中的Leu含量超过4%会导致生长发育迟缓和肝脏重量减轻,而给予相同剂量的12%或40%蛋白质的Leu不会影响它们。通过系统的数据提取过程,确定了6个候选基因标记。从另一项在低蛋白饮食中使用0、2、3、4和8%Leu的实验获得的肝基因表达数据,用于通过接受者工作特征(ROC)曲线分析检查这些生物标志物候选物的有效性。生物标志物候选物的所有AUC值均大于0.700,表明标志物候选物作为Leu过量指数的有效性。通过基因标记的多元回归分析获得的基因标记面板的ROC曲线的临界值表明,Leu水平高于3%会产生不利影响。总之,基因标记专家小组建议,对于雄性大鼠,低蛋白(6%)饮食中的膳食Leu补充量为2%是NOAEL剂量。

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