Elucidation of the Interaction between Nutrition and the Gene Expression Control System Based on "Omics" Analyses

为了扩展膳食蛋白质影响的转录组学分析，检查了蛋白质营养对脂肪组织基因表达谱的影响。认为蛋白质营养不良时，PPARγ基因的上调与胰岛素敏感性的升高有关。此外，还利用基因芯片对一些动物蛋白进行了功能分析。分析了氨基酸剥夺对肝癌细胞转录组和蛋白质组的影响。许多基因被发现直接响应于氨基酸;它们包括一些转录因子和翻译因子的基因。然后，我们探讨了组学方法的应用过量的氨基酸的毒性作用。结果表明，在胱氨酸过量的情况下，肝脏和心脏是其毒性作用的主要靶点。然后详细研究了氨基酸对转录和翻译的调控机制。Foxos和ATF等转录因子被证明发挥了重要作用。根据介导因子IRS-1研究了氨基酸调节胰岛素信号通路的机制。本研究还尝试将转录组学应用于食品安全性评价，为营养基因组学研究探索新的方向。低过敏性小麦粉的安全性证实了这种技术，显示了这种方法的有效性。建立营养基因组学数据库是营养基因组学研究的重要内容。建立并公布了一个独特的数据库。正在积累DNA微阵列分析的原始数据和营养基因组学实验的出版信息。

To extend the transcriptomic analysis of the effect of dietary protein, the effect of protein nutrition on the gene expression profile of adipose tissue was examined. The up-regulation of the PPARγ gene was thought to be involved in the elevated sensitivity to insulin under protein malnutrition. Additionally, function analysis of some animal proteins was carried out by using a DNA microarray. Then the effect of amino acid deprivation on transcriptome and proteome of a hepatoma cell line was analyzed. Many genes were found to directly respond to amino acids; they included the genes for some transcription factors and translation factors. We then explored the application of omics approach to the toxic effect of the excess of an amino acid. The result indicated that, in the case of cystine excess, the liver and heart are major targets of its toxic effect. The regulatory mechanisms of transcription and translation by amino acids were then examined in detail. Transcription factors such as Foxos and ATFs turned out to play important roles. The mechanism whereby amino acids regulate the signaling pathway of insulin was studied in light of a mediating factor, IRS-1. We could propose a novel regulatory mechanism of cell signaling in which amino acids serves as regulators of some phosphatases.Moreover, to explore a new direction of omics analyses in nutrigenomics area, we attempted to use transcriptomics for the evaluation of the safety of food. The safety of hypoallergenic wheat flour was confirmed with this technique, showing the effectiveness of this approach. It seemed to be essential to build a nutrigenomics database for efficient development of nutrigenomics area. A unique database was created and publicized. Raw data of DNA microarray analyses and publication information on nutrigenomics experiments are being accumulated.