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Molecular Mechanism of Metabolic Memory via a DNA Methylation and Its Medical Application

Research Project

Project/Area Number 23390240
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Metabolomics
Research InstitutionTokyo Medical and Dental University

Principal Investigator

OGAWA Yoshihiro  東京医科歯科大学, 医歯(薬)学総合研究科, 教授 (70291424)

Co-Investigator(Renkei-kenkyūsha) OKANO Masaki  理化学研究所, 発生・再生科学総合研究センター, チームリーダー (50360863)
Project Period (FY) 2011-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥19,370,000 (Direct Cost: ¥14,900,000、Indirect Cost: ¥4,470,000)
Fiscal Year 2013: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2012: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2011: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
KeywordsDNAメチル化 / 肝臓 / 脂肪酸β酸化 / PPARα / 新規脂肪合成 / 新生仔 / 脂肪酸β酸化経路 / エピゲノム / 脂肪合成
Research Abstract

In this study, we analyzed epigenetic regulation of lipid metabolism in mouse liver in perinatal periods. In neonatal periods, DNA methylation of de novo lipogenic glycerol-3-phosphate acyltransferase 1 (GPAT1) gene (Gpam) promoter suppresses the gene expression, whereas Gpam expression is induced in the weaning period via a DNA demethylation mechanism. This suggests de novo mouse hepatic lipogenesis in perinatal periods is regulated by DNA methylation. We also analyzed DNA methylation in neonatal mouse liver from the birth to weaning. It revealed that fatty acid beta-oxidation enzymes were highlighted among the genes, which showed DNA demethylation and increased gene expression in postnatal periods. We also demonstrated that the DNA demethylation is peroxisome proliferator-activated receptor (PPAR)-alpha dependent. This study shed a light on the importance of intrinsic lipid ligands in milk in the epigenetic regulation of lipid metabolism in perinatal mouse liver.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (35 results)

All 2014 2013 2012 2011 2010 Other

All Journal Article (16 results) (of which Peer Reviewed: 4 results) Presentation (11 results) (of which Invited: 6 results) Book (4 results) Remarks (4 results)

  • [Journal Article] 内分泌基礎分野での進歩胎児期~新生児期の環境とエピジェネティクス制御2014

    • Author(s)
      亀井康富, 橋本貢士, 小川佳宏
    • Journal Title

      AnnualReview 糖尿病・代謝・内分泌

      Volume: 2014 Pages: 138-144

    • Related Report
      2013 Final Research Report
  • [Journal Article] Analysis of DNA methylation change induced by Dnmt3b in mouse hepatocytes2013

    • Author(s)
      Takahashi M, Kamei Y, Ehara T, Yuan X, Suganami T, Takai-Igarashi T, Hatada I, Ogawa Y
    • Journal Title

      Biochem. Biophy. Res. Commun

      Volume: 434 Pages: 873-878

    • Related Report
      2013 Final Research Report
  • [Journal Article] Glucose-independent persistence of PAI-1 gene expression and H3K4 tri-methylation in type 1 diabetic mouse endothelium : implication in metabolic memory2013

    • Author(s)
      Takizawa F, Mizutani S, Ogawa Y, Sawada N
    • Journal Title

      Biochem. Biophys. Res. Commun

      Volume: 433 Pages: 66-72

    • Related Report
      2013 Final Research Report
  • [Journal Article] Association between body weight at weaning and remodeling in the subcutaneous adipose tissue of obese adult mice with undernourishment in utero2013

    • Author(s)
      Kohmura YK, Kanayama N, Muramatsu K, Tamura N, Yaguchi C, Uchida T, Suzuki K, Sugihara K, Aoe S, Sasaki T, Suganami T, Ogawa Y, Itoh H
    • Journal Title

      Reprod. Sci

      Volume: 20 Pages: 813-827

    • Related Report
      2013 Final Research Report
  • [Journal Article] Activin receptor-like kinase 7 suppresses lipolysis to accumulate fat in obesity through downregulation of peroxisome proliferator-activated receptor γ and C/EBPα2013

    • Author(s)
      Yogosawa S, Mizutani S, Ogawa Y, Izumi T
    • Journal Title

      Diabetes

      Volume: 62 Pages: 115-123

    • Related Report
      2013 Final Research Report
  • [Journal Article] 基礎講座体質からみた糖尿病ジェネティクス・エピジェネティクス糖尿病とエピジェネティクス2013

    • Author(s)
      亀井康富, 小川佳宏
    • Journal Title

      Diabetes Frontier

      Volume: 24 Pages: 447-452

    • Related Report
      2013 Final Research Report
  • [Journal Article] 【エピジェネティクスと病気】(第2章)エピジェネティクスと病気環境相互作用・多因子疾患糖尿病2013

    • Author(s)
      亀井康富, 小川佳宏
    • Journal Title

      遺伝子医学MOOK

      Volume: 25 Pages: 112-116

    • Related Report
      2013 Final Research Report
  • [Journal Article] Analysis of DNA methylation change induced by Dnmt3b in mouse hepatocytes2013

    • Author(s)
      Takahashi M, Kamei Y, Ehara T, Yuan X, Suganami T, Takai-Igarashi T, Hatada I, Ogawa Y
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 434 Issue: 4 Pages: 873-878

    • DOI

      10.1016/j.bbrc.2013.04.041

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Glucose-independent persistence of PAI-1 gene expression and H3K4 tri-methylation in type 1 diabetic mouse endothelium: implication in metabolic memory.2013

    • Author(s)
      Takizawa F, Mizutani S, Ogawa Y, Sawada N.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 433(1) Issue: 1 Pages: 66-72

    • DOI

      10.1016/j.bbrc.2013.02.064

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Association between body weight at weaning and remodeling in the subcutaneous adipose tissue of obese adult mice with undernourishment in utero2013

    • Author(s)
      Y.K. Kohmura, N. Kanayama, K. Muramatsu, N. Tamura, C. Yaguchi, T. Uchida, K. Suzuki, K. Sugihara, S. Aoe, T. Sasaki, T. Suganami, Y. Ogawa, H. Itoh
    • Journal Title

      Reprod. Sci.

      Volume: 20 Issue: 7 Pages: 813-827

    • DOI

      10.1177/1933719112466300

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Activin receptor-like kinase 7 suppresses lipolysis to accumulate fat in obesity through downregulation of peroxisome proliferator-activated receptorγ and C/EBPα2013

    • Author(s)
      Yogosawa S, Mizutani S, Ogawa Y, Izumi T
    • Journal Title

      Diabetes

      Volume: 62 Issue: 1 Pages: 115-123

    • DOI

      10.2337/db12-0295

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 糖尿病とエピジェネティクス2013

    • Author(s)
      亀井康富、小川佳宏
    • Journal Title

      Diabetes Frontier

      Volume: 24 Pages: 447-452

    • Related Report
      2013 Annual Research Report
  • [Journal Article] Role of DNA methylation in the regulation of lipogenic glycerol-3-phosphate acyltransferase 1 gene expression in the mouse neonatal liver2012

    • Author(s)
      Ehara T, Kamei Y, Takahashi M, Yuan X, Kanai S, Tamura E, Tanaka M, Yamazaki T, Miura S, Ezaki O, Suganami T, Okano M, Ogawa Y
    • Journal Title

      Diabetes

      Volume: 61 Pages: 2442-2450

    • Related Report
      2013 Final Research Report 2012 Annual Research Report 2011 Annual Research Report
  • [Journal Article] 【糖尿病とその合併症の成因~最新の知見~】エピゲノムと糖尿病2012

    • Author(s)
      亀井康富, 小川佳宏
    • Journal Title

      最新医学

      Volume: 67 Pages: 27-31

    • Related Report
      2013 Final Research Report
  • [Journal Article] エピゲノムと糖尿病2012

    • Author(s)
      亀井康富
    • Journal Title

      最新医学

      Volume: 67 Pages: 27-31

    • Related Report
      2012 Annual Research Report 2011 Annual Research Report
  • [Journal Article] 【世代を超えて伝わる代謝エピジェネティクス】栄養環境と代謝のエピジェネティクス2011

    • Author(s)
      江原達弥, 亀井康富, 高橋真由美, 袁勲梅, 小川佳宏
    • Journal Title

      実験医学

      Volume: 29 Pages: 2217-2222

    • Related Report
      2013 Final Research Report
  • [Presentation] Regulation of Metabolic Genes by DNA Methylation2013

    • Author(s)
      Ogawa Y
    • Organizer
      8th World Congress on Developmental Origins of Health and Disease
    • Place of Presentation
      SUNTEC, Singapore
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Invited
  • [Presentation] 乳仔期のマウス肝臓における代謝関連遺伝子のDNAメチル化変動の解析2013

    • Author(s)
      江原達弥, 亀井康富, 袁勳梅, 高橋真由美, 田村江梨奈, 菅波孝祥, 高井貴子, 畑田出穂, 橋本貢士, 小川佳宏
    • Organizer
      第34回日本肥満学会
    • Place of Presentation
      東京
    • Related Report
      2013 Final Research Report
  • [Presentation] 栄養とエピゲノム肝臓脂質代謝のエピジェネティクス制御2013

    • Author(s)
      亀井康富, 江原達弥, 高橋真由美, 袁勲梅, 小川佳宏
    • Organizer
      第67回日本栄養・食糧学会大会
    • Place of Presentation
      名古屋
    • Related Report
      2013 Final Research Report
  • [Presentation] 肝臓における糖脂質代謝のエピゲノム制御2013

    • Author(s)
      小川佳宏
    • Organizer
      第56回日本糖尿病学会年次学術集会
    • Place of Presentation
      熊本
    • Related Report
      2013 Final Research Report
    • Invited
  • [Presentation] 肝臓における糖脂質代謝のエピゲノム制御2013

    • Author(s)
      小川佳宏
    • Organizer
      第56回日本糖尿病学会年次学術集会
    • Place of Presentation
      熊本、日本
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 肝臓における脂質代謝のエピゲノム2012

    • Author(s)
      小川佳宏
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡
    • Related Report
      2013 Final Research Report
    • Invited
  • [Presentation] マウス新生仔肝臓の脂肪合成遺伝子のDNAメチル化制御2012

    • Author(s)
      亀井康富, 江原逹弥, 高橋真由美, 袁勲梅, 金井紗綾香, 山崎聖美, 江崎治, 菅波孝祥, 岡野正樹, 小川佳宏
    • Organizer
      第66回日本栄養・食糧学会大会
    • Place of Presentation
      仙台
    • Related Report
      2013 Final Research Report
  • [Presentation] 栄養環境がもたらすエピゲノム変化2012

    • Author(s)
      小川佳宏, 亀井康富
    • Organizer
      第6回日本エピジェネティクス研究会年会
    • Place of Presentation
      東京
    • Related Report
      2013 Final Research Report 2012 Annual Research Report 2011 Annual Research Report
    • Invited
  • [Presentation] 肝臓における脂質代謝のエピゲノム制御2012

    • Author(s)
      小川佳宏
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡
    • Related Report
      2012 Annual Research Report 2011 Annual Research Report
    • Invited
  • [Presentation] 栄養とエピジェネティクス生活習慣病とDNAメチル化2011

    • Author(s)
      亀井康富, 小川佳宏
    • Organizer
      第65回日本栄養・食糧学会大会
    • Place of Presentation
      東京
    • Related Report
      2013 Final Research Report
  • [Presentation] グリセロール3リン酸アシル基転移酵素(GPAT1)遺伝子のDNAメチル化による発現制御2010

    • Author(s)
      江原達弥, 亀井康富, 金井紗綾香, 高橋真由美, 袁勲梅, 菅波孝祥, 小川佳宏
    • Organizer
      第31回日本肥満学会
    • Place of Presentation
      前橋
    • Related Report
      2013 Final Research Report
  • [Book] 疾患とエピジェネティクス糖尿病イラストで徹底理解するエピジェネティクスキーワード事典(牛島俊和, 眞貝洋一編)2013

    • Author(s)
      橋本貢士, 小川佳宏
    • Publisher
      羊土社
    • Related Report
      2013 Final Research Report
  • [Book] 栄養とエピジェネティクス-食による身体変化と生活習慣病の分子構造-ネスレ栄養科学会議監修2012

    • Author(s)
      小川佳宏, 加藤茂明, 塩田邦郎, 中尾光善, 酒井寿郎, 福岡秀興共著
    • Publisher
      建帛社
    • Related Report
      2013 Final Research Report
  • [Book] 栄養とエピジェネティクス-食による身体変化と生活習慣病の分子構造-2012

    • Author(s)
      亀井康富
    • Total Pages
      141
    • Publisher
      健帛社
    • Related Report
      2012 Annual Research Report
  • [Book] 栄養とエピジェネティクス-食による身体変化と生活習慣病の分子構造-2012

    • Author(s)
      亀井康富
    • Total Pages
      141
    • Publisher
      建帛社
    • Related Report
      2011 Annual Research Report
  • [Remarks] 東京医科歯科大学大学院医歯学総合研究科分子内分泌代謝学分野

    • URL

      http://www.tmd.ac.jp/grad/cme/index.html

    • Related Report
      2013 Final Research Report
  • [Remarks] 東京医科歯科大学大学院医歯学総合研究科分子内分泌代謝学分野

    • URL

      http://www.tmd.ac.jp/grad/cme/index.html

    • Related Report
      2013 Annual Research Report
  • [Remarks] 東京医科歯科大学 大学院医歯学総合研究科 分子内分泌代謝学分野

    • URL

      http://www.tmd.ac.jp/grad/cme/index.html

    • Related Report
      2012 Annual Research Report
  • [Remarks] 東京医科歯科大学 大学院医歯学総合研究科 分子内分泌代謝学分野

    • URL

      http://www.tmd.ac.jp/grad/cme/index.html

    • Related Report
      2011 Annual Research Report

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Published: 2011-04-06   Modified: 2019-07-29  

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