Development of epigenome biomakers reflecting the eating habit

• Project/Area Number: 26282027
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Eating habits
• Research Institution: University of Shizuoka
• Principal Investigator: GODA Toshinao 静岡県立大学, 食品栄養科学部, 教授 (70195923)
• Co-Investigator(Kenkyū-buntansha): 市川 陽子 静岡県立大学, 食品栄養科学部, 准教授 (50269495) ; 望月 和樹 山梨大学, 総合研究部, 准教授 (80423838) ; 本間 一江 静岡県立大学, 食品栄養科学部, 助教 (80724765)
• Co-Investigator(Renkei-kenkyūsha): KOBAYASHI Kimiko 静岡県立大学, 食品栄養科学部, 教授 (90215319)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000); Fiscal Year 2016: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2014: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
• Keywords: エピゲノム / バイオマーカー / 食後高血糖 / 慢性炎症 / 末梢血

Outline of Final Research Achievements

We have demonstrated using animal models of type two diabetes and obesity that the history of postprandial hyperglycemia is reflected by a change in the responding capability regarding the expression of the genes related to inflammation and insulin resistance in the peripheral leukocytes and the liver. The mononuclear cells exposed to a high glucose concentration for 24h showed persistently elevated levels of the mRNA and histone H3 acetylation (an epigenetic modification) of TNFa gene, which plays a pivotal role in inflammation and insulin resistance. Candidates of epigenome biomarkers for the history of postprandial glucose spikes include a hepatocyte-derived micro RNA and plasma soluble cell adhesion molecules.

Research Products

• [Journal Article] Insulin-induced inhibition of gluconeogenesis genes, including glutamic pyruvic transaminase 2, is associated with reduced histone acetylation in a human liver cell line. (2017)
  • Author(s): Honma, K., Kamikubo, M., Mochizuki, K., Goda, T.
  • Journal Title: Metabolism Volume: 印刷中 Pages: 118-124
  • DOI: 10.1016/j.metabol.2017.03.009
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Fasting for 3 days during the suckling-weaning transient period in male rats induces metabolic abnormalities in the liver and is associated with impaired glucose tolerance in adulthood. (2016)
  • Author(s): Ikeda M, Honma K, Mochizuki K, and Goda T.
  • Journal Title: Eur J Nutr Volume: 55(3） Issue: 3 Pages: 1059-67
  • DOI: 10.1007/s00394-015-0919-9
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Fasting during the suckling-weaning transient period of rats induces inflammatory gene expression in the adipose tissue and peripheral leukocytes. (2016)
  • Author(s): Honma, K., Mawatari, R., Ikeda, M., Mochizuki, K., Goda, T.
  • Journal Title: Nutrition Volume: 32 Issue: 11-12 Pages: 1268-1274
  • DOI: 10.1016/j.nut.2016.03.011
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Transcription elongation factor Brd4-P-TEFb accelerates intestinal differentiation-associated SLC2A5 gene expression. (2016)
  • Author(s): Inamochi, Y., Dey, A., Nishiyama, A., Kubota, T., Ozato, K., Goda, T., Mochizuki, K.
  • Journal Title: Biochemistry and Biophysics Reports Volume: 7 Pages: 150-156
  • Peer Reviewed
• [Journal Article] Brd4 regulates fructose-inducible lipid accumulation-related genes in the mouse liver. (2016)
  • Author(s): Yamada, A., Honma, K., Mochizuki, K., Goda, T.
  • Journal Title: Metabolism Volume: 65 Issue: 10 Pages: 1478-1488
  • DOI: 10.1016/j.metabol.2016.07.001
  • Peer Reviewed
• [Journal Article] Glycemic response in healthy Japanese subjects after consuming potatoes and white rice. (2016)
  • Author(s): Wakasugi, Y., Hashidume, S., Sano, A., Mochizuki, K., Goda, T., Ichikawa, Y.
  • Journal Title: J. ARAHE Volume: 23 (1) Pages: 1-8
  • Peer Reviewed
• [Journal Article] ChREBP binding and histone modifications modulate hepatic expression of the Fasn gene in a metabolic syndrome rat model. (2015)
  • Author(s): Suzuki T, Muramatsu T, Morioka K, Goda T, Mochizuki K.
  • Journal Title: Nutrition Volume: 31(6) Issue: 6 Pages: 877-83
  • DOI: 10.1016/j.nut.2015.01.005
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Plasma TNF-α is associated with inflammation and nutritional status in community-dwelling Japanese elderly (2015)
  • Author(s): Oe Y., Mochizuki K., Miyauchi R., Misaki Y., Kasezawa N., Tohyama K., Goda T.
  • Journal Title: J. Nutr. Sci. Vitaminol. Volume: 61 Pages: 263-269
  • NAID: 130005089922
  • Peer Reviewed
• [Journal Article] Serum fatty acid binding protein 4 concentrations are positively and independently associated with blood pressure and abdominal fat among parameters health check-ups in middle-aged general Japanese males. (2015)
  • Author(s): Yamada M., Mochizuki K., Honma K., Miyauchi R., Kasezawa N., Tohyama K., Goda T.
  • Journal Title: J. Nutr. Sci. Vitaminol. Volume: 61 Pages: 291-298
  • Peer Reviewed
• [Journal Article] Treatment with DPP-4I anagliptin or α-GI miglitol reduces IGT development and the expression of CVD risk factors in OLETF rats. (2015)
  • Author(s): Imai C., Harazaki T., Inoue S., Mochizuki K., Goda T.
  • Journal Title: J. Nutr. Sci. Vitaminol. Volume: 61 Pages: 313-321
  • NAID: 130005102612
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Polymorphism in microRNA-binding site in HNF1B influences the susceptibility of type 2 diabetes mellitus: a population based case-control study (2015)
  • Author(s): N. Goda, H. Murase, N. Kasezawa, T. Goda, K. Yamakawa-Kobayashi
  • Journal Title: BMC Medical Genetics Volume: 16 Issue: 1 Pages: 75-75
  • DOI: 10.1186/s12881-015-0219-5
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Induction of histone H3K4 methylation at the promoter, enhancer, and transcribed regions of the Si and Sglt1 genes in rat jejunum in response to a high-starch/low-fat diet. (2015)
  • Author(s): Inoue, S., Honma, K., Mochizuki, K., Goda, T
  • Journal Title: Nutrition Volume: 31 Issue: 2 Pages: 366-372
  • DOI: 10.1016/j.nut.2014.07.017
  • Peer Reviewed
• [Journal Article] Putative PPAR target genes express highly in skeletal muscle of insulin-resistant MetS model SHR/NDmc-cp rats. (2015)
  • Author(s): Hariya, N., Miyake, K., Kubota, T., Goda, T., Mochizuki, K.
  • Journal Title: J. Nutr. Sci. Vitaminol. Volume: 61 Pages: 28-36
  • NAID: 130005070830
  • Peer Reviewed
• [Journal Article] Fasting for 3 days during the suckling-weaning transient period in male rats induces metabolic abnormalities in the liver and associated with impaired glucose tolerance. (2015)
  • Author(s): Ikeda, M., Honma, K., Mochizuki, K., Goda, T.
  • Journal Title: Eur. J. Nutr. Volume: 未定
  • Peer Reviewed
• [Journal Article] 幼少期栄養環境とバイオマーカー (2015)
  • Author(s): 合田敏尚
  • Journal Title: 最新医学 Volume: 70 Pages: 918-923
• [Journal Article] Bindings of ChREBP and SREBP1, and histone acetylation around the rat liver fatty acid synthase gene are associated with induction of the gene during suckling-weaning transition. (2014)
  • Author(s): Morishita, S., Mochizuki, K., Goda, T.
  • Journal Title: J. Nutr. Sci. Vitaminol. Volume: 60 Pages: 94-100
  • NAID: 130004491371
  • Peer Reviewed
• [Journal Article] Re-feeding rats a high-sucrose diet after 3 days starvation enhances histone H3 acethylation in transcribed region and expression of jejunal GLUT5 gene. (2014)
  • Author(s): Honma, K., Masuda, Y., Mochizuki, K., Goda, T.
  • Journal Title: Biosci. Biotechnol. Biochem. Volume: 78 Pages: 1771-1773
  • Peer Reviewed
• [Journal Article] Switching Insulin α-glucosidase inhibitors to miglitol reduced glucose fluctuations and circulating cardiovascular disease risk factors in type 2 diabetic Japanese patients. (2014)
  • Author(s): Hariya N., Mochizuki K., Inoue S., Saito M., Fuchigami M., Goda T.
  • Journal Title: Drugs R. D. Volume: 14 Issue: 3 Pages: 177-184
  • DOI: 10.1007/s40268-014-0055-7
  • Peer Reviewed
• [Journal Article] Self-reported faster eating is positively associated with accumulation of visceral fat in middle-aged apparently healthy Japanese men. (2014)
  • Author(s): Mochizuki K., Yamada M., Miyauchi R., Misaki Y., Kasezawa N., Tohyama K., Goda T.
  • Journal Title: Eur. J. Nutr. Volume: 53 Issue: 5 Pages: 1187-1194
  • DOI: 10.1007/s00394-013-0619-2
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Molecular regulations of mucosal maltase expressions (2016)
  • Author(s): Goda, T.
  • Organizer: Starch digestion consortium workshop: Complimentary starch feeding of the young child
  • Place of Presentation: Houston, USA
  • Year and Date: 2016-12-05
  • Int'l Joint Research / Invited
• [Presentation] Combination therapy with α-glucosidase inhibitor and DPP-4 inhibitor in patients with type 2 diabetes mellitus. (2016)
  • Author(s): Honma K., Mochizuki K., Osonoi T., Saito M., Goda T.
  • Organizer: The 21th Shizuoka Forum on Health and Longevity
  • Place of Presentation: 静岡
  • Year and Date: 2016-11-25
• [Presentation] 好中球エラスターゼ活性阻害剤の食後高血糖動物モデルへの投与は動脈硬化関連遺伝子の発現を低下させる (2016)
  • Author(s): 今井千裕，望月和樹，合田敏尚
  • Organizer: 第59回日本糖尿病学会年次学術集会
  • Place of Presentation: 京都
  • Year and Date: 2016-05-20
• [Presentation] ヒストンアセチル化を介した小腸消化吸収関連遺伝子の転写制御 (2016)
  • Author(s): 本間一江，鈴木友莉，山田有紀，望月和樹，合田敏尚
  • Organizer: 第70回日本栄養・食糧学会大会
  • Place of Presentation: 兵庫
  • Year and Date: 2016-05-15
• [Presentation] 糖刺激によるBRD4-ヒストンアセチル化依存的転写伸長の増進機構 (2015)
  • Author(s): 望月和樹, 合田敏尚, 久保田健夫
  • Organizer: 第38回日本分子生物学会年会 第88回日本生化学会大会 合同学会
  • Place of Presentation: 神戸
  • Year and Date: 2015-12-03
  • Invited
• [Presentation] 新規エピゲノム因子Brd4を介した単回のグルコース応答性炎症関連遺伝子の発現持続機構 (2015)
  • Author(s): 今井千裕, 望月和樹, 久保田健夫, 合田敏尚
  • Organizer: 第38回日本分子生物学会年会 第88回日本生化学会大会 合同学会
  • Place of Presentation: 神戸
  • Year and Date: 2015-12-03
• [Presentation] フルクトース誘導性の肝臓代謝関連遺伝子のBrd4を介した発現調節機構 (2015)
  • Author(s): 山田有紀, 本間一江, 望月和樹, 久保田健夫, 合田敏尚
  • Organizer: 第38回日本分子生物学会年会 第88回日本生化学会大会 合同学会
  • Place of Presentation: 神戸
  • Year and Date: 2015-12-03
• [Presentation] Suppression of the vascular endothelial damage-related genes by inhibiting neutrophil elastase activity in type 2 diabetic model OLETF rats. (2015)
  • Author(s): Imai C., Mochizuki K., Goda T.
  • Organizer: The 20th Shizuoka Forum on Health and Longevity
  • Place of Presentation: Shizuoka, Japan
  • Year and Date: 2015-10-30
  • Int'l Joint Research
• [Presentation] Regulation of fructose inducible genes in the liver by the bromodomain protein Brd4. (2015)
  • Author(s): Yamada A., Honma K., Mochizuki K., Goda T.
  • Organizer: The 20th Shizuoka Forum on Health and Longevity
  • Place of Presentation: Shizuoka, Japan
  • Year and Date: 2015-10-30
  • Int'l Joint Research
• [Presentation] 低栄養ストレスによる発達期の2型糖尿病発症メカニズム～転写因子FOXO1を介した異所性脂肪細胞分化～ (2015)
  • Author(s): 針谷夏代, 望月和樹, 久保田健夫, 合田敏尚
  • Organizer: 第4回日本DOHaD研究会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2015-08-02
• [Presentation] 2型糖尿病自然発症OLETFラットへのアナグリプチンの長期投与は肝臓における白血球浸潤マーカーの発現を抑制する (2015)
  • Author(s): 今井千裕, 原崎友美, 井上聖哉, 望月和樹, 合田敏尚
  • Organizer: 第58日本糖尿病学会年次学術集会
  • Place of Presentation: 山口
  • Year and Date: 2015-05-22
• [Presentation] エピゲノム因子Brd4は肝臓と骨格筋におけるインスリンシグナル伝達経路に関与する (2015)
  • Author(s): 山田有紀, 山田真実, 本間一江, 望月和樹, 合田敏尚
  • Organizer: 第58日本糖尿病学会年次学術集会
  • Place of Presentation: 山口
  • Year and Date: 2015-05-21
• [Presentation] Putative PPAR target genes express highly in skeletal muscle of insulin-resistant MetS model SHR/NDmc-cp rats. (2015)
  • Author(s): Hariya N., Miyake K., Kubota T., Goda T., Mochizuki K.
  • Organizer: 12th Asian Congress of Nutrition
  • Place of Presentation: Yokohama, JAPAN
  • Year and Date: 2015-05-15
  • Int'l Joint Research
• [Presentation] The effect of starvation in weaning period on dietrelated changes in the expression of inflammation-related genes in the adipose tissue. (2015)
  • Author(s): Honma K., Mawatari R., Ikeda M., Mochizuki K., Goda T.
  • Organizer: 12th Asian Congress of Nutrition
  • Place of Presentation: Yokohama, Japan
  • Year and Date: 2015-05-15
  • Int'l Joint Research
• [Presentation] フルクトースによる肝臓脂肪合成関連遺伝子の発現変動におけるブロモドメインタンパク質Brd4の関与 (2014)
  • Author(s): 山田有紀ら
  • Organizer: 第67回日本栄養・食糧学会中部支部大会
  • Place of Presentation: 静岡
  • Year and Date: 2014-11-22
• [Presentation] The effect of starvation in weaning period on diet-related changes in the expression of inflammation-related genes in peripheral leukocytes. (2014)
  • Author(s): 本間一江ら
  • Organizer: The 19th Shizuoka Forum on Health and Longevity
  • Place of Presentation: 静岡
  • Year and Date: 2014-11-07
• [Presentation] Identification of the SNPs altering microRNA binding affinity in the type 2 diabetes susceptible genes. (2014)
  • Author(s): 合田直樹ら
  • Organizer: The 19th Shizuoka Forum on Health and Longevity
  • Place of Presentation: 静岡
  • Year and Date: 2014-11-07
• [Presentation] Transient high glucose exposure promotes subsequent inductions of inflammation-related genes and the histone acetylation around the genes in human monocyte-like THP-1 cell. (2014)
  • Author(s): 今井千裕ら
  • Organizer: The 19th Shizuoka Forum on Health and Longevity
  • Place of Presentation: 静岡
  • Year and Date: 2014-11-07
• [Presentation] Pharm-food efficacy and epigenetic inflammation biomarkers. (2014)
  • Author(s): 合田敏尚
  • Organizer: The 2nd International Conference on Pharma and Food
  • Place of Presentation: 静岡
  • Year and Date: 2014-11-06
  • Invited
• [Presentation] 生活習慣病バイオマーカーを活用したDOHaDへの先制医療 (2014)
  • Author(s): 合田敏尚
  • Organizer: 第3回日本DOHaD研究会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2014-07-26
  • Invited
• [Presentation] 短期間の高グルコース刺激がヒト単球様THP-1細胞の炎症関連遺伝子の発現に及ぼす影響 (2014)
  • Author(s): 今井千裕ら
  • Organizer: 第3回日本DOHaD研究会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2014-07-25
• [Presentation] 離乳期の低栄養による小腸糖質消化吸収関連遺伝子の食事に対する応答性の変化 (2014)
  • Author(s): 藤井貴子ら
  • Organizer: 第3回日本DOHaD研究会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2014-07-25
• [Presentation] 離乳期低栄養とその後の食餌組成が末梢血白血球における炎症関連遺伝子の発現に及ぼす影響 (2014)
  • Author(s): 本間一江ら
  • Organizer: 第68回日本栄養・食糧学会大会
  • Place of Presentation: 札幌
  • Year and Date: 2014-06-01
• [Presentation] 糖質摂取制限による空腸マルターゼ・グルコアミラーゼ遺伝子のヒストン修飾を介した発現抑制機構 (2014)
  • Author(s): 下田恭子ら
  • Organizer: 第68回日本栄養・食糧学会大会
  • Place of Presentation: 札幌
  • Year and Date: 2014-05-31
• [Presentation] 短期間の2型糖尿病モデルOLETFラットの骨格筋における代謝制御シグナルに及ぼすDPP-4阻害薬の影響 (2014)
  • Author(s): 内山弓子ら
  • Organizer: 第57日本糖尿病学会年次学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2014-05-23
• [Book] 幼少期栄養環境とバイオマーカー (2015)
  • Author(s): 合田敏尚
  • Total Pages: 6
  • Publisher: 最新医学社 最新醫學, 70(5), 82-87
• [Book] Gene body 領域のエピゲノム修飾に基づいた代謝関連遺伝子の発現制御機構 (2015)
  • Author(s): 望月和樹, 針谷夏代, 本間一江, 合田敏尚, 久保田健夫
  • Total Pages: 6
  • Publisher: 北隆館 Bio Clinica, 30 (9), 83-88
• [Remarks] 静岡県立大学教員データベース
  • URL: http://db.u-shizuoka-ken.ac.jp/show/prof151.html
• [Remarks] 栄養生理学研究室HP
  • URL: http://dfns.u-shizuoka-ken.ac.jp/labs/nutrphys/