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

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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.