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Search for epigenome markers associated with an elevated risk of diabetes due to undernutrition in the fetal period

Research Project

Project/Area Number 16K12727
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Eating habits
Research InstitutionUniversity 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) 本間 一江  静岡県立大学, 食品栄養科学部, 助教 (80724765)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords胎児期低栄養 / 糖尿病 / エピゲノム / バイオマーカー / 胎児期 / 低栄養
Outline of Final Research Achievements

We have demonstrated that the undernutrition in the late fetal period in the rat leads to a reduced expression of ontogeny/differentiation-related genes in the pancreas, and a repressed expression of the genes coding transcription factors related to adipocyte differentiation in the adipose tissue, which should be respectively responsible for reduced insulin secretion and insulin sensitivity. In an animal strain predisposed to a reduced capability of insulin secretion, the undernutrition in the fetal period made worse the postprandial hyperglycemia in adulthood.
In search of the genes responding closely to postprandial hyperglycemia in the peripheral leukocytes of rats subjected to undernutrition in the fetal period, we have shown that inflammation-related genes, e.g., IL-1b, S100a8, S100a9 and S100a11, are putatively sensitive marker genes reflecting a postprandial hyperglycemic history

Academic Significance and Societal Importance of the Research Achievements

本研究の学術的な意義は、胎児期の低栄養環境が、出生後の発達の過程で膵臓ならびに脂肪組織における分化や成熟化に関わる遺伝子の発現の低下をもたらすため、糖負荷による急激な血糖上昇が起こりやすく、糖尿病のリスクを高めることを示したことと、胎児期の低栄養環境による血糖上昇の履歴を示す候補遺伝子として炎症性サイトカイン遺伝子を同定したことである。
本研究は、遺伝素因の点で膵臓からのインスリン分泌能力の低い日本人にとって、妊娠時の栄養管理と胎児期における低栄養の予防が、糖尿病の発症・進展リスクの抑制のために、いかに重要かの根拠の一端を提示したものである。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (31 results)

All 2018 2017 2016 Other

All Journal Article (11 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 11 results,  Open Access: 4 results,  Acknowledgement Compliant: 5 results) Presentation (17 results) (of which Int'l Joint Research: 5 results,  Invited: 3 results) Book (1 results) Remarks (2 results)

  • [Journal Article] The induction of CHD1 binding and methylation histone H3 K4 methylation on SI gene is associated with the gene expression in enterocyte-like Caco-2 cells.2018

    • Author(s)
      Mochizuki K, Osaki A, Inamochi Y, Goda T.
    • Journal Title

      OBM Genetics

      Volume: 2 Issue: 4 Pages: 1-1

    • DOI

      10.21926/obm.genet.1804046

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Regulation of the circadian rhythmic expression of Sglt1 in the mouse small intestine through histone acetylation and the mRNA elongation factor, BRD4-P-TEFb2018

    • Author(s)
      Yamauchi Hiroyuki、Honma Kazue、Mochizuki Kazuki、Goda Toshinao
    • Journal Title

      Bioscience, Biotechnology, and Biochemistry

      Volume: 印刷中 Issue: 7 Pages: 1-4

    • DOI

      10.1080/09168451.2018.1451743

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Molecular regulations of mucosal maltase expressions2018

    • Author(s)
      Goda Toshinao, Honma Kazue
    • Journal Title

      Journal of Pediatric Gastroenterology and Nutrition

      Volume: 66 (suppl 3)

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] BRD4 regulates adiponectin gene induction by recruiting the P-TEFb complex to the transcribed region of the gene2017

    • Author(s)
      Sakurai Naoko、Inamochi Yuko、Inoue Takuya、Hariya Natsuyo、Kawamura Musashi、Yamada Masami、Dey Anup、Nishiyama Akira、Kubota Takeo、Ozato Keiko、Goda Toshinao、Mochizuki Kazuki
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 11962-11962

    • DOI

      10.1038/s41598-017-12342-2

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Relationship between epigenetic regulation, dietary habits, and the Developmental Origins of Health and Disease theory.2017

    • Author(s)
      Mochizuki K, Hariya N, Honma K, Goda T.
    • Journal Title

      Congenit Anom (Kyoto).

      Volume: Web掲載 Issue: 6 Pages: 14781488-14781488

    • DOI

      10.1111/cga.12213

    • NAID

      130008142297

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / 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

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Loss of circadian rhythm of circulating insulin concentration induced by high-fat diet intake is associated with disrupted rhythmic expression of circadian clock genes in the liver.2016

    • Author(s)
      Honma K, Hikosaka M, Mochizuki K, Goda T.
    • Journal Title

      Metabolism

      Volume: 65(4) Issue: 4 Pages: 482-491

    • DOI

      10.1016/j.metabol.2015.12.003

    • Related Report
      2016 Research-status Report
    • 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

    • Related Report
      2016 Research-status Report
    • 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

    • Related Report
      2016 Research-status Report
    • 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

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Presentation] インスリン抵抗性に対する栄養学的アプローチ2018

    • Author(s)
      合田敏尚、本間一江
    • Organizer
      第72回日本栄養・食糧学会大会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 非肥満型2型糖尿病モデルGK ラットにおける膵臓機能に及ぼす胎児期低栄養の影響2018

    • Author(s)
      合田敏尚、金芳如、倉橋美帆、本間一江
    • Organizer
      第61回糖尿病学会年次学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 胎児期低栄養モデルラットにおける末梢血白血球の炎症性サイトカイン発現の変化2018

    • Author(s)
      金芳如、瀧賀祐生、本間一江、合田敏尚
    • Organizer
      第61回糖尿病学会年次学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 新規転写伸長エピゲノム調節機構と胎生期低栄養による生活習慣病発症との関連2018

    • Author(s)
      望月和樹、針谷 夏代、本間 一江、合田 敏尚、久保田 健夫
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 末梢血白血球における炎症性サイトカイン遺伝子周辺のメチル化DNA検出方法の検討2018

    • Author(s)
      瀧賀祐生、金芳如、本間一江、合田敏尚
    • Organizer
      第72回日本栄養・食糧学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ラットの脂肪組織の遺伝子発現に及ぼす胎児期低栄養の影響2018

    • Author(s)
      金芳如、小池美帆、本間一江、合田敏尚
    • Organizer
      第75回日本栄養・食糧学会中支部大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Epigenetic alterations of inflammation biomarkers related with the onset and development of diabetes and metabolic diseases2017

    • Author(s)
      Goda Toshiao
    • Organizer
      The 12th China-Japan International Symposium
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Fasting during the suckling-weaning transient period in rats induces metabolic abnormalities in adulthood2017

    • Author(s)
      Honma Kazue, Ikeda Misa, Mawatari Riko, Mochizuki Kazuki, Goda Toshinao
    • Organizer
      21st International Congress of Nutrition (ICN2017)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Plasma alanine aminotransferase (ALT) activity is a reliable biomarker for the risk of insulin resistance and diabetes predisposition2017

    • Author(s)
      Goda Toshinao, Honma Kazuki, Tohyama Kazushige, Mochizuki Kazuki
    • Organizer
      21st International Congress of Nutrition (ICN2017)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 非肥満型2型糖尿病モデルGKラットにおける膵臓機能に及ぼす胎児期低栄養の影響2017

    • Author(s)
      久保田美成,倉橋美帆,金芳加,本間一江,合田敏尚
    • Organizer
      第6回日本DOHaD学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] Molecular regulations of mucosal maltase expressions2016

    • 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
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Effect of prenatal undernutrition on BCMO1 gene expression in rat jejunum at suckling-weaning period2016

    • Author(s)
      Matsumoto K., Honma K., Goda T.
    • Organizer
      The 3rd International Conference on Pharma and Food
    • Place of Presentation
      Shizuoka
    • Year and Date
      2016-11-18
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 発達期の小腸におけるβカロテン代謝関連酵素発現への胎児期低栄養の影響2016

    • Author(s)
      本間一江,松本氣寧子,望月和樹, 合田敏尚
    • Organizer
      第5回日本DOHaD研究会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2016-07-23
    • Related Report
      2016 Research-status Report
  • [Presentation] Relations between epigenetic regulation by dietary habits and DOHaD2016

    • Author(s)
      望月和樹,針谷夏代,本間一江,合田敏尚
    • Organizer
      第56回日本先天異常学会学術集会
    • Place of Presentation
      兵庫
    • Year and Date
      2016-07-01
    • Related Report
      2016 Research-status Report
  • [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
    • Related Report
      2016 Research-status Report
  • [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
    • Related Report
      2016 Research-status Report
  • [Presentation] 胎児期低栄養が哺乳-離乳期の小腸消化吸収関連遺伝子発現に及ぼす影響2016

    • Author(s)
      松本氣寧子,本間一江,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
      2016-05-14
    • Related Report
      2016 Research-status Report
  • [Book] Handbook of Nutrition, Diet, and Epigenetics2018

    • Author(s)
      Mochizuki Kazuki、Hariya Natsuyo、Honma Kazue、Goda Toshinao
    • Publisher
      Springer International Publishing AG
    • Related Report
      2018 Annual Research Report
  • [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

    • Related Report
      2018 Annual Research Report
  • [Remarks] 栄養生理学研究室HP

    • URL

      http://dfns.u-shizuoka-ken.ac.jp/labs/nutrphys/

    • Related Report
      2018 Annual Research Report

URL: 

Published: 2016-04-21   Modified: 2020-03-30  

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