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

• Project/Area Number: 15380090
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Food science
• Research Institution: The University of Tokyo
• Principal Investigator: KATO Hisanori The University of Tokyo, Graduate School of Agricultural and Life Sciences, Associate Professor, 大学院・農学生命科学研究科, 助教授 (40211164)
• Co-Investigator(Kenkyū-buntansha): YOSHIZAWA Fumiaki Utsunomiya University, Faculty of Agriculture, Associate Professor, 農学部, 助教授 (10269243)
• Project Period (FY): 2003 – 2005
• Project Status: Completed (Fiscal Year 2005)
• Budget Amount: ¥15,800,000 (Direct Cost: ¥15,800,000); Fiscal Year 2005: ¥3,500,000 (Direct Cost: ¥3,500,000); Fiscal Year 2004: ¥4,600,000 (Direct Cost: ¥4,600,000); Fiscal Year 2003: ¥7,700,000 (Direct Cost: ¥7,700,000)
• Keywords: transcriptomics / nutrigenomics / proteomics / amino acids / dietary protein / food safety / transcription factor / database / トランスクリプトーム / 遺伝子発現 / 大豆タンパク質 / 低アレルゲン化小麦粉 / 食品の安全性 / インスリン

Research Abstract

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.

Research Products

• [Journal Article] Safety evaluation of a hypoallergenic wheat flour using DNA microarray. (2006)
  • Author(s): Narasaka, S., Endo, Y., Fu, ZW., Moriyama, M., Arai, S., Abe, K., Kato, H.
  • Journal Title: Biosci. Biotechnol. Biochem. 70・6(印刷中)
  • NAID: 10018530351
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Intravenous administration of amino acids during anesthesia stimulates muscle protein synthesis and heat accumulation in the body. (2006)
  • Author(s): Yamaoka I., Doi M., Nakayama M., Ozeki A., Mochizuki S., Sugahara K., Yoshizawa F.
  • Journal Title: Am J Physiol Endocrinol Metab. 290・5(印刷中)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Safety evaluation of a hypoallergenic wheat flour using DNA microarray. (2006)
  • Author(s): Narasaka, S., Endo, Y., Fu, ZW., Moriyama, M., Arai, S., Abe, K., Kato, H.
  • Journal Title: Biosci.Biotechnol.Biochem. 70(印刷中)
  • NAID: 10018530351
• [Journal Article] Biosci. Biotechnol. Biochem. (2005)
  • Author(s): Hirao, T., Imai, S., Sawada, H., Shiomi, N., Hachimura, S., Kato, H.
  • Journal Title: PCR method for detecting trace amounts of buckwheat (Fagopyrum spp.) in food. 69・4 Pages: 724-731
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] J. Agric. Food Chem. (2005)
  • Author(s): Tachibana, N., Matsumoto, I., Fukui, K., Arai, S., Kato, H., Abe, K.
  • Journal Title: Intake of soy protein isolate alters hepatic gene expression in rats. 53・10 Pages: 4253-4257
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Disruption of the availability of amino acids induces a rapid reduction of serine phosphorylation of insulin receptor substrate-1 in vivo and in vitro. (2005)
  • Author(s): Ohne, Y., Toyoshima, Y., Kato, H.
  • Journal Title: Biosci. Biotechnol. Biochem. 69・5 Pages: 989-998
  • NAID: 130000030331
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] A nutrigenomics database - Integrated repository for publications and associated microarray data in nutrigenomics research. (2005)
  • Author(s): Saito, K., Arai, S., Kato, H.
  • Journal Title: Brit. J. Nutr. 94・4 Pages: 496-495
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] A perspective on DNA microarray technology in food and nutritional science. (2005)
  • Author(s): Kato, H., Saito, K., Kimura, T.
  • Journal Title: Curr. Opin. Clin. Nutr. Metab. Care 8・5 Pages: 516-522
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Transcriptomics and metabolomics of diertary leucine excess. (2005)
  • Author(s): Matsuzaki, K., Kato, H., Sakai, R., Toue, S., Amao, M., Kimura, T.
  • Journal Title: J. Nutr. 135・6 Pages: 1571-1575
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Effect of orally administered branched-chain amino acids on protein synthesis and degradation in rat skeletal muscle. (2005)
  • Author(s): Yoshizawa F., Nagasawa T., Sugahara K.
  • Journal Title: Asian-Aust. J. Animal. Sci. 18・1 Pages: 133-140
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Adaptive changes in translation initiation activities for rat pancreatic protein synthesis with feeding of a high-protein diet. (2005)
  • Author(s): Hashi M., Yoshizawa F., Onozuka E., Ogata M., Hara H.
  • Journal Title: J. Nutr. Biochem. 16・8 Pages: 507-512
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Isoleucine, a blood glucose-lowering amino acid, increases glucose uptake in rat skeletal muscle in the absence of increases in AMP-activated protein kinase activity. (2005)
  • Author(s): Doi M., Yamaoka I., Nakayama M., Mochizuki S., Sugahara K., Yoshizawa F.
  • Journal Title: J. Nutr. 135・9
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] PCR method for detecting trace amounts of buckwheat (Fagopyrum spp.) in food. (2005)
  • Author(s): Hirao, T., Imai, S., Sawada, H., Shiomi, N., Hachimura, S., Kato, H.
  • Journal Title: Biosci.Biotechnol.Biochem. 69-4 Pages: 724-731
  • NAID: 130000030353
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Intake of soy protein isolate alters hepatic gene expression in rats. (2005)
  • Author(s): Tachibana, N., Matsumoto, I., Fukui, K., Arai, S., Kato, H., Abe, K.
  • Journal Title: J.Agric.Food Chem. 53-10 Pages: 4253-4257
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Disruption of the availability of amino acids induces a rapid reduction of serine phosphorylation of insulin receptor substrate-1 in vivo and in vitro. (2005)
  • Author(s): Ohne, Y., Toyoshima, Y., Kato, H.
  • Journal Title: Biosci.Biotechnol.Biochem. 69-5 Pages: 989-998
  • NAID: 130000030331
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A nutrigenomics database Integrated repository for publications and associated microarray data in nutrigenomics research. (2005)
  • Author(s): Saito, K., Arai, S., Kato, H.
  • Journal Title: Brit.J.Nutr. 94-4 Pages: 493-495
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A perspective on DNA microarray technology in food and nutritional science. (2005)
  • Author(s): Kato, H., Saito, K., Kimura, T.
  • Journal Title: Curr.Opin.Clin.Nutr.Metab.Care 8-5 Pages: 516-522
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Transcriptomics and metabolomics of dietary leucine excess. (2005)
  • Author(s): Matsuzaki, K., Kato, H., Sakai, R., Toue, S., Amao, M., Kimura, T.
  • Journal Title: J.Nutr. 135-6 Pages: 1571-1575
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Effect of orally administered branched-chain amino acids on protein synthesis and degradation in rat skeletal muscle. (2005)
  • Author(s): Yoshizawa F., Nagasawa T., Sugahara K.
  • Journal Title: Asian-Aust.J.Animal.Sci. 18-1 Pages: 133-140
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Adaptive changes in translation initiation activities for rat pancreatic protein synthesis with feeding of a high-protein diet. (2005)
  • Author(s): Hashi M., Yoshizawa F., Onozuka E., Ogata M., Hara H.
  • Journal Title: J.Nutr.Biochem. 16-8 Pages: 507-512
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Isoleucine, a blood glucose-lowering amino acid, increases glucose uptake in rat skeletal muscle in the absence of increases in AMP-activated protein kinase activity. (2005)
  • Author(s): Doi M., Yamaoka I., Nakayama M., Mochizuki S., Sugahara K., Yoshizawa F.
  • Journal Title: J.Nutr. 135-9 Pages: 2103-2108
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A nutrigenomics database - Integrated repository for publications and associated microarray data in nutrigenomics research. (2005)
  • Author(s): Saito, K., Arai, S., Kato, H.
  • Journal Title: British Journal of Nutrition 94 Pages: 493-495
• [Journal Article] Transcriptomics and metabolomics of dietary leucine excess. (2005)
  • Author(s): Matsuzaki, K., Kato, H., Sakai, R., Toue, S., Amao, M., Kimura, T.
  • Journal Title: Journal of Nutrition 135 Pages: 1571-1575
• [Journal Article] Isoleucine, a blood glucose-lowering amino acid, increases glucose uptake in rat skeletal muscle in the absence of increases in AMP-activated protein kinase activity. (2005)
  • Author(s): Doi M., Yamaoka I., Nakayama M., Mochizuki S., Sugahara K., Yoshizawa F.
  • Journal Title: Journal of Nutrition 135 Pages: 2103-2108
• [Journal Article] DNA microarray analyses of the effects of dietary proteins. (2005)
  • Author(s): Kato, H., Narasaka, S., Endo, Y., Abe, K., Arai, S.
  • Journal Title: Biofactors 21 Pages: 11-13
• [Journal Article] Disruption of the Availability of Amino Acids Induces a Rapid Reduction of Serine Phosphorylation of Insulin Receptor Substrate-1 in Vivo and in Vitro (2005)
  • Author(s): Ohne, Y., Toyoshima, Y., Kato, H.
  • Journal Title: Biosci.Biotechnol.Biochem. 69(印刷中)
  • NAID: 130000030331
• [Journal Article] J. Mol. Endocrinol. (2004)
  • Author(s): Toyoshima, Y., Ohne, Y., Takahashi, S.-I., Noguchi, T., Kato, H.
  • Journal Title: Dietary protein deprivation decreases the serine phosphorylation of insulin receptor substrate-1 in rat skeletal muscle. 32・2 Pages: 519-531
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Briofactors (2004)
  • Author(s): Kato, H., Narasaka, S., Endo, Y., Abe, K., Arai, S.
  • Journal Title: DNA microarray analyses of the effects of dietary proteins. 21・1 Pages: 11-13
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Dietary protein deprivation decreases the serine phosphorylation of insulin receptor substrate-1 in rat skeletal muscle. (2004)
  • Author(s): Toyoshima, Y., Ohne, Y., Takahashi, S.-I., Noguchi, T., Kato, H.
  • Journal Title: J.Mol.Endocrinol. 32-2 Pages: 519-531
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] DNA microarray analyses of the effects of dietary proteins. (2004)
  • Author(s): Kato, H., Narasaka, S., Endo, Y., Abe, K., Arai, S.
  • Journal Title: Biofactors 21-1 Pages: 11-13
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Dietary protein deprivation decreases the serine phosphorylation of insulin receptor substrate-1 in rat skeletal muscle (2004)
  • Author(s): Toyoshima, Y., Ohne, Y., Takahashi, S.-I., Noguchi, T., Kato.
  • Journal Title: J.Mol.Endocrinol. 31 Pages: 519-531
• [Journal Article] Biosci. Biotechnol. Biochem. (2003)
  • Author(s): Oishi, Y., Kato, H., Noguchi, T.
  • Journal Title: Dietary protein is a potent regulator of the hyaluronan synthase gene in rat skin. 67・4 Pages: 736-742
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] J. Nutr. (2003)
  • Author(s): Kato, H., Kimura, T.
  • Journal Title: Evaluation of the effects of the dietary intake of proteins and amino acids by DNA microarray technology. 133・6
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Dietary protein is a potent regulator of the hyaluronan synthase gene in rat skin. (2003)
  • Author(s): Oishi, Y., Kato, H., Noguchi, T.
  • Journal Title: Biosci.Biotechnol.Biochem. 67-4 Pages: 736-742
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Evaluation of the effects of the dietary intake of proteins and amino acids by DNA microarray technology. (2003)
  • Author(s): Kato, H., Kimura, T.
  • Journal Title: J.Nutr. 133-6
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Safety evaluation of a hypoallergenic wheat flour using DNA microarray.
  • Author(s): Narasaka, S., Endo, Y., Fu, ZW., Moriyama, M.Arai, S., Abe, K., Kato, H.
  • Journal Title: Biosci.Biotechnol.Biochem. 70-6 (in press)
  • NAID: 10018530351
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Intravenous administration of amino acids during anesthesia stimulates muscle protein synthesis and heat accumulation in the body.
  • Author(s): Yamaoka I., Doi M., Nakayama M., Ozeki A., Mochizuki S., Sugahara K., Yoshizawa F.
  • Journal Title: Am J Physiol Endocrinol Metab. 290-5 (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Book] 健康栄養学-健康科学としての栄養生理化学 (2005)
  • Author(s): 小田裕昭, 加藤久典, 関泰一郎
  • Total Pages: 237
  • Publisher: 共立出版
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Imae, M., Fu, ZW., Yoshida, A., Noguchi, T., Kato, H.: "Nutritional and hormonal factors control the gene expression of FoxOs, the mammalian homologues of DAF-16."J.Mol.Endocrinol.. 30. 253-262 (2003)
• [Publications] Toyoshima, Y., Ohne, Y., Takahashi, S.-I., Noguchi, T., Kato, H.: "Dietary protein deprivation decrease the serine phosphorylation of insulin receptor substrate-1 in rat skeletal muscle"J.Mol.Endocrinol.. (印刷中). (2004)