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Analysis of pathological roles of hypoxic responses in the regulation of organ metabolism in fatty liver diseases

Research Project

Project/Area Number 23590370
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pathological medical chemistry
Research InstitutionWaseda University

Principal Investigator

GODA Nobuhito  早稲田大学, 理工学術院, 教授 (00245549)

Co-Investigator(Renkei-kenkyūsha) TSUKADA Kosuke  慶應義塾大学, 理工学部, 准教授 (00351883)
KABE Yasuaki  慶應義塾大学, 医学部, 講師 (20397037)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords脂質代謝 / 低酸素応答 / 脂肪肝 / HIF / 肝臓 / 低酸素 / ペルオキシゾーム / lipin-1 / 肝線維化 / 糖代謝
Research Abstract

In this study, we aimed to elucidate roles of hypoxic responses in the development and progression of fatty liver diseases evoked by excessive alcohol and high-fat diets. We found that hypoxia inducible factor1 (HIF1), a master regulator of hypoxic responses, serves as a protective mechanism against aberrant lipid accumulation in both alcoholic and non-alcoholic fatty liver in mice, whereas it promotes liver fibrosis in the latter stage of the disease. These results provide an important evidence that successful regulations of hypoxic response by targeting HIF1 can control the development of fatty liver and its related diseases such as liver cirrhosis and cancer.

Report

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

    (63 results)

All 2013 2012 2011 Other

All Journal Article (15 results) (of which Peer Reviewed: 15 results) Presentation (29 results) (of which Invited: 3 results) Book (17 results) Remarks (2 results)

  • [Journal Article] Regulation of glycolysis by Pdk functions as a metabolic checkpoint for cell cycle quiescence in hematopoietic stem cells.2013

    • Author(s)
      Takubo K
    • Journal Title

      Cell Stem Cell

      Volume: 12 Issue: 1 Pages: 49-61

    • DOI

      10.1016/j.stem.2012.10.011

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Adipose Tissue Hypoxia Induces Inflammatory M1 Polarity of Macrophages in HIF-1a-Dependent and HIF-1a-Independent Manners in Obese Mice.2013

    • Author(s)
      Fujisaka S, Usui I, Ikutani M, Aminuddin A, Takikawa A, Tsuneyama K, Mahmood A, Goda N, Nagai Y, Takatsu K, Tobe K..
    • Journal Title

      Diabetologia

      Volume: 56(6) Issue: 6 Pages: 1403-1412

    • DOI

      10.1007/s00125-013-2885-1

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Metabolomic profiling analysis reveals chamber-dependent metabolite patterns in the mouse heart.2013

    • Author(s)
      Shimura D, Nakai G, Jiao Q, Osanai K, Kashikura K, Endo K, Soga T, Goda N, Minamisawa S
    • Journal Title

      American Journal of Physiology, Heart and Circul atory Physiology

      Volume: 305(4) Issue: 4 Pages: H494-H505

    • DOI

      10.1152/ajpheart.00867.2012

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hypoxia-inducible factor-1 is a determinant of lobular structure and oxygen consumption in the liver.2013

    • Author(s)
      Tsukada K, Tajima T, Hori S, Matsuura T, Johnson RS, Goda N, Suematsu M.
    • Journal Title

      Microcirculation

      Volume: in press Issue: 5 Pages: 385-393

    • DOI

      10.1111/micc.12033

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Hypoxia-inducible factors and their roles in energy metabolism.2012

    • Author(s)
      Goda N, Kanai M.
    • Journal Title

      Int J Hematol

      Volume: 95 Issue: 5 Pages: 457-463

    • DOI

      10.1007/s12185-012-1069-y

    • NAID

      10030632790

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] HIF-1αinduction suppresses excessive lipid accumulation in alcoholic fatty liver in mice2012

    • Author(s)
      Nishiyama Y, Goda N, 他9名
    • Journal Title

      J Hepatol

      Volume: 56(2) Issue: 2 Pages: 441-447

    • DOI

      10.1016/j.jhep.2011.07.024

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] HIF-1 in T cells ameliorated dextran sodium sulfate-induced murine colitis.2012

    • Author(s)
      Higashiyama M, Hokari R, Hozumi H, Kurihara C, Ueda T, Watanabe C, Tomita K, Nakamura M, Komoto S, Okada Y, Kawaguchi A, Nagao S, Suematsu M, Goda N, Miura S.
    • Journal Title

      J Leukoc Biol

      Volume: 91(6) Issue: 6 Pages: 901-909

    • DOI

      10.1189/jlb.1011518

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Hypoxia biology in health and disease2012

    • Author(s)
      Goda N
    • Journal Title

      Int J Hematol

      Volume: 95 Issue: 5 Pages: 455-456

    • DOI

      10.1007/s12185-012-1084-z

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] HIF-1a induction suppresses excessive lipid accumulation in alcoholic fatty liver in mice.2012

    • Author(s)
      Nishiyama Y
    • Journal Title

      J Hepatol

      Volume: 56(2) Pages: 441-447

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Dynamic regulation of Th17 differentiation by oxygen concentrations.2012

    • Author(s)
      Ikejiri A
    • Journal Title

      Int Immunol

      Volume: 24(3) Pages: 137-146

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] The formation of an angiogenic astrocyte template is regulated by the neuroretina in a HIF-1-dependent manner.2012

    • Author(s)
      Nakamura-Ishizu A
    • Journal Title

      Dev Biol

      Volume: 363(1) Pages: 106-114

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] A role for endothelial cells in promoting the maturation of astrocytes through the apelin/APJ system in mice.2012

    • Author(s)
      Sakimoto S
    • Journal Title

      Development

      Volume: 139(7) Pages: 1327-1335

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Disruption of HIF-1α in Hepatocytes Impairs Glucose Metabolism in Diet-induced Obesity Mice2011

    • Author(s)
      Ochiai, D.
    • Journal Title

      Biochem.Biophys.Res.Commun

      Volume: 415 Issue: 3 Pages: 445-449

    • DOI

      10.1016/j.bbrc.2011.10.089

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Disruption of HIF-1a in hepatocytes impairs glucose metabolism in diet-induced obesity mice.2011

    • Author(s)
      Ochiai D
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 415(3) Pages: 445-449

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Heterofunctional nanosheet controlling cell adhesion properties by collagen coating.2011

    • Author(s)
      Niwa D
    • Journal Title

      J Biomater Appl

      Volume: in press

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] 低酸素応答システムによる代謝制御2013

    • Author(s)
      合田亘人
    • Organizer
      第50回日本臨床分子医学会
    • Place of Presentation
      東京
    • Related Report
      2013 Final Research Report
  • [Presentation] HIF-1 Regulates Hepatic Lipid Metabolism in a Context-dependent Manner2012

    • Author(s)
      Nobuhito Goda
    • 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 2012 Research-status Report
  • [Presentation] 低酸素応答による肝代謝機能制御2012

    • Author(s)
      合田亘人
    • Organizer
      第19回肝細胞研究会
    • Place of Presentation
      札幌
    • Related Report
      2013 Final Research Report
  • [Presentation] Role of HIF-1 in the regulation of hepatic lipid metabolism2012

    • Author(s)
      Nobuhito Goda
    • Organizer
      The 33^<rd> NAITO CONFERENCE ON OXYGEN BIOLOGY:HYPOXIA, OXIDATIVE STRESS AND DISEASES
    • Place of Presentation
      SAPPPORO
    • Related Report
      2013 Final Research Report
  • [Presentation] 肝代謝制御における低酸素応答の機能解析2011

    • Author(s)
      合田亘人
    • Organizer
      第84回日本生化学会総会
    • Place of Presentation
      京都
    • Related Report
      2013 Final Research Report 2011 Research-status Report
  • [Presentation] Functional Analysis of ALS2/Alsin in a Drosophila Familial Amyotrophic Lateral Sclerosis Model2011

    • Author(s)
      Tsutsumi K
    • Organizer
      The 1st Asia-Pacific Drosophila Research Conference
    • Place of Presentation
      Taipei
    • Related Report
      2011 Research-status Report
  • [Presentation] Analysis of competitive interactions during proliferation and cell death via dMyc-mediated regulation.2011

    • Author(s)
      Senoo-Matsuda N
    • Organizer
      The 1st Asia-Pacific Drosophila Research Conference
    • Place of Presentation
      Taipei
    • Related Report
      2011 Research-status Report
  • [Presentation] Deletion of hepatic HIF-1a gene aggravated alcohol-induced steatosis in mice2011

    • Author(s)
      Goda N
    • Organizer
      International Symposium on ALPD and Cirrhosis
    • Place of Presentation
      Fukuoka
    • Related Report
      2011 Research-status Report
  • [Presentation] ショウジョウバエモデルを用いたSima/HIF-1aシグナルが関わる神経変性疾患の発症機構の解明2011

    • Author(s)
      大野 貴久
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Related Report
      2011 Research-status Report
  • [Presentation] ショウジョウバエモデルを用いたSima/HIF-1aシグナルによる個体の大きさの制御機構の解析2011

    • Author(s)
      平本 美香子
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Related Report
      2011 Research-status Report
  • [Presentation] 2型筋萎縮性側索硬化症モデルショウジョウバエを用いたALS2/Alsinの神経保護作用の解析2011

    • Author(s)
      堤 香菜子
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Related Report
      2011 Research-status Report
  • [Presentation] Relevance of mitochondrial bioenergetics to in vitro megakaryocyte differentiation2011

    • Author(s)
      Kanai M
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Related Report
      2011 Research-status Report
  • [Presentation] 低酸素応答システムによる代謝制御

    • Author(s)
      合田 亘人
    • Organizer
      第50回日本臨床分子医学会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 低酸素応答性転写制御因子HIF-1を介した非アルコール性脂肪肝抑制機構の解明

    • Author(s)
      合田 亘人
    • Organizer
      第49回日本肝臓学会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] Protective role of hepatic HIF-1 against liver steatosis in non-alcoholic fatty liver disease

    • Author(s)
      Nobuhito Goda
    • Organizer
      Keystone Symposia
    • Place of Presentation
      Colorado
    • Related Report
      2013 Annual Research Report
  • [Presentation] Hypoxic response and lipid metabolism

    • Author(s)
      Nobuhito Goda
    • Organizer
      International Symposium on Integration of Chemistry and Bioscience
    • Place of Presentation
      Tokyo
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 低酸素応答システムを介した非アルコール性脂肪性肝疾患の発症制御機構

    • Author(s)
      合田 亘人、新井 理智、加藤 祐樹
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] アルコール性脂肪肝の発症機構における低酸素応答の病態生理学的意義

    • Author(s)
      合田 亘人
    • Organizer
      第48回日本肝臓学会総会
    • Place of Presentation
      金沢
    • Related Report
      2012 Research-status Report
  • [Presentation] Role of HIF-1 in the regulation of hepatic lipid metabolism

    • Author(s)
      Nobuhito Goda
    • Organizer
      The 33rd NAITO CONFERENCE ON OXYGEN BIOLOGY: HYPOXIA, OXIDATIVE STRESS AND DISEASES
    • Place of Presentation
      札幌
    • Related Report
      2012 Research-status Report
  • [Presentation] 低酸素応答による肝代謝機能制御

    • Author(s)
      合田 亘人
    • Organizer
      第19回肝細胞研究会
    • Place of Presentation
      札幌
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] Hypoxic responses and alcoholic fatty liver

    • Author(s)
      Nobuhito Goda
    • Organizer
      16th Congress of International Society for Biomedical Research on Alcoholism
    • Place of Presentation
      札幌
    • Related Report
      2012 Research-status Report
  • [Presentation] HIF-1 regulates lipid metabolism in the liver

    • Author(s)
      Nobuhito Goda
    • Organizer
      New Frontiers of Metabolism Research in Biomedical Sciences
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Presentation] コリン欠乏食誘導性NAFLDモデルにおけるHIF1の機能解析

    • Author(s)
      新井理智、加藤祐樹、合田亘人
    • Organizer
      第85回日本生化学会総会
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report
  • [Presentation] ショウジョウバエモデルを用いたSima/HIF-1aシグナルによる個体の発生と老化の制御機構の解析

    • Author(s)
      平本美香子、大野貴久、合田亘人、松田七美
    • Organizer
      第85回日本生化学会総会
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report
  • [Presentation] Biological roles of HIFs in the maintenance of carbohydrate metabolism in liver

    • Author(s)
      加藤早由華、合田亘人
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report
  • [Presentation] Pathological Mechanism of ALS2/Alsin in a Drosophila Familial Amyotrophic Lateral Sclerosis Model

    • Author(s)
      府川直矢、堤香菜子、合田亘人、松田七美
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report
  • [Presentation] Mechanism of in body size control via Sima/HIF-1α signaling in Drosophila

    • Author(s)
      平本美香子、大野貴久、合田亘人、松田七美
    • Organizer
      第10回 日本ショウジョウバエ研究会
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Presentation] Functional analysis of Sima/HIF-1α signaling in Drosophila neurodegenerative disease models

    • Author(s)
      大野貴久、合田亘人、松田七美
    • Organizer
      第10回 日本ショウジョウバエ研究会
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Presentation] 心不全紀副腎におけるマクロファージの浸潤とアルドステロン異常産生

    • Author(s)
      伊藤健太郎、佐野元昭、三谷芙美子、Yan Xiaoian、松橋智弘、勝俣良紀、安西淳、木内謙一郎、竹島亜希子、吉田尚弘、山本恒久、新村健、合田亘人、福田恵一
    • Organizer
      第三回Molecular Cardiovascular ConferenceII
    • Place of Presentation
      北海道余市郡
    • Related Report
      2012 Research-status Report
  • [Book] 医学のあゆみ244(4)2013

    • Author(s)
      合田亘人, 加藤早由華
    • Publisher
      医歯薬出版
    • Related Report
      2013 Final Research Report
  • [Book] 医学のあゆみ2013

    • Author(s)
      合田 亘人、加藤 早由華
    • Publisher
      医師薬出版株式会社
    • Related Report
      2013 Annual Research Report
  • [Book] 細胞2013

    • Author(s)
      合田 亘人
    • Publisher
      ニュー・サイエンス社
    • Related Report
      2013 Annual Research Report
  • [Book] 人生化学84(11)2012

    • Author(s)
      合田亘人
    • Related Report
      2013 Final Research Report
  • [Book] 血管医学Vascular Biology & Medicine 13(4)2012

    • Author(s)
      合田亘人, 長内康太
    • Publisher
      メディカルレビュー社
    • Related Report
      2013 Final Research Report
  • [Book] 実験医学30(8)2012

    • Author(s)
      合田亘人, 鈴木智大, 金井麻衣
    • Publisher
      羊土社
    • Related Report
      2013 Final Research Report
  • [Book] HIFが制御するエネルギー代謝2012

    • Author(s)
      合田 亘人、鈴木 智大、金井 麻衣
    • Publisher
      羊土社 実験医学
    • Related Report
      2012 Research-status Report
  • [Book] 概論-多彩な生命現象に働く低酸素応答システム2012

    • Author(s)
      中山 恒、合田 亘人
    • Publisher
      羊土社 実験医学
    • Related Report
      2012 Research-status Report
  • [Book] 低酸素シグナリング -HIFシグナリング-2012

    • Author(s)
      合田 亘人、金井 麻衣
    • Publisher
      羊土社 イラストで徹底理解するシグナル伝達キーワード事典
    • Related Report
      2012 Research-status Report
  • [Book] 低酸素転写制御因子とSDB2012

    • Author(s)
      合田 亘人、鈴木 智大
    • Publisher
      ライフサイエンス出版 呼吸器NEWS&VIEWS
    • Related Report
      2012 Research-status Report
  • [Book] 肝疾患とHIFを介した低酸素応答2012

    • Author(s)
      合田 亘人、長内 康太
    • Publisher
      メディカルレビュー社 血管医学Vascular Biology & Medicine
    • Related Report
      2012 Research-status Report
  • [Book] HIFによる肝臓内糖・脂質代謝制御機構2012

    • Author(s)
      合田 亘人
    • Publisher
      生化学
    • Related Report
      2012 Research-status Report
  • [Book] HIFを介した防御機構:低酸素ストレス下のエネルギー代謝制御2012

    • Author(s)
      合田 亘人、加藤 早由華
    • Publisher
      医歯薬出版株式会社 医学のあゆみ
    • Related Report
      2012 Research-status Report
  • [Book] 実験医学29(13)2011

    • Author(s)
      合田亘人, 金井麻衣
    • Publisher
      羊土社
    • Related Report
      2013 Final Research Report
  • [Book] アルコールと医学生物学302011

    • Author(s)
      合田亘人
    • Publisher
      東洋出版
    • Related Report
      2013 Final Research Report
  • [Book] 実験医学 肝細胞の不均一性と肝代謝制御2011

    • Author(s)
      合田 亘人
    • Publisher
      羊土社
    • Related Report
      2011 Research-status Report
  • [Book] アルコールと医学生物学 アルコール性脂肪肝における低酸素応答性転写制御因子HIF-1の機能解析2011

    • Author(s)
      合田 亘人
    • Publisher
      東洋書店
    • Related Report
      2011 Research-status Report
  • [Remarks]

    • URL

      http://www.waseda.jp/sem-godalab/

    • Related Report
      2013 Final Research Report
  • [Remarks] 合田研究室

    • URL

      http://www.waseda.jp/sem-godalab/

    • Related Report
      2013 Annual Research Report

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Published: 2011-08-05   Modified: 2019-07-29  

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