Genetic and epigenetic differences in cholesterol kinetics in relation to NASH development between SHRSP and SHRSP5/Dmcr rat

• Project/Area Number: 22790543
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Hygiene
• Research Institution: Nagoya University
• Principal Investigator: NAITO Hisao 名古屋大学, 大学院・医学系研究科, 助教 (90547556)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2010: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 肝線維化 / 非アルコール性脂肪性肝疾患 / コレステロール / 胆汁酸 / 核内受容体 / トリグリセライド / BSEP / MRP3 / 薬物代謝酵素 / HRP3

Research Abstract

This study aims to clarify the differences in molecular mechanisms of the cholesterol and bile acid kinetics in the progression of high fat-cholesterol diet(HFC)-induced steatohepatitis and fibrosis between SHRSP5/Dmcr and SHRSP rats. In the result, SHRSP5/Dmcr may be more susceptible to liver fibrosis than SHRSP, which may be resulted from the higher intracellular accumulation of cytotoxic bile acid by decreased BSEP expression, though increased MRP3.

Research Products

• [Journal Article] Modulation of hepatic adenosine triphosphate and inflammation by eicosapentaenoic acid under severe fibrosis progression in SHRSP5/Dmcr (2012)
  • Author(s): Jia X, Naito H, Yetti H, Tamada H, Kitamori K, Hayashi Y, Yamagishi N, Wang D, Yanagiba Y, Ito Y, Wang J, Tanaka N, Ikeda K, Yamori Y, Nakajima T
  • Journal Title: Life Sci Volume: (in press)
  • Peer Reviewed
• [Journal Article] Simultaneous changes in high-fat and high-cholesterol diet-induced steatohepatitis and severe fibrosis and those underlying molecular mechanisms in novel SHRSP5/Dmcr rat (2012)
  • Author(s): Moriya T, Kitamori K, Naito H, Yanagiba Y, Ito Y, Yamagishi N, Tamada H, Jia X, Tsuchikura S, Ikeda K, Yamori Y, Nakajima T
  • Journal Title: Environ Health Prev Med
  • NAID: 10031135721
  • Peer Reviewed
• [Journal Article] Simultaneous changes in high-fat and high-cholesterol diet-induced steat ohepatitis and severe fibrosis and those underlying molecular mechanisms in novel SHRSP5/Dmcr rat (2012)
  • Author(s): Moriya T
  • Journal Title: Environ Health Prev Med Volume: (印刷中)(in press) Issue: 6 Pages: 444-456
  • DOI: 10.1007/s12199-012-0273-y
  • Peer Reviewed
• [Journal Article] Differences in metabolite burden of di(2-ethylhexy)phthalate in pregnant and postpartum dams and their offspring in relation to drug-metabolizing enzymes in mice (2012)
  • Author(s): Hayashi Y
  • Journal Title: Arch Toxicol Volume: (印刷中)(in press) Issue: 4 Pages: 563-569
  • DOI: 10.1007/s00204-011-0790-2
  • Peer Reviewed
• [Journal Article] Development of novel rat model for high-fat and high-cholesterol diet-induced steatohepatitis and severe fibrosis progression in SHRSP5/Dmcr. (2012)
  • Author(s): Kitamori K
  • Journal Title: Environ Health Prev Med. Volume: May;17(3) Issue: 3 Pages: 173-82
  • DOI: 10.1007/s12199-011-0235-9
  • NAID: 10030616942
  • Peer Reviewed
• [Journal Article] Modulation of ammonium perfluorooctanoate-induced hepatic damage by genetically different PPARαin mice. (2012)
  • Author(s): Nakagawa T, Ramdhan DH, Tanaka N, Naito H, Tamada H, Ito Y, Li YF, Hayashi Y, Yamagishi N, Yanagiba Y, Aoyama T, Gonzalez FJ, Nakajima T
  • Journal Title: Arch Toxicol Volume: 86 Issue: 1 Pages: 63-74
  • DOI: 10.1007/s00204-011-0704-3
  • Peer Reviewed
• [Journal Article] Development of novel rat model for high-fat and high-cholesterol diet-induced steatohepatitis and severe fibrosis progression in SHRSP5/Dmcr (2011)
  • Author(s): Kitamori K, Naito H, Tamada H, Kobayashi M, Miyazawa D, Yasui Y, Sonoda K, Tsuchikura S, Yasui N, Ikeda K, Moriya T, Yamori Y, Nakajima T
  • Journal Title: Environ Health Prev Med
  • NAID: 10030616942
  • Peer Reviewed
• [Journal Article] Study profile on baseline survey of Daiko Study in the Japan Multi-Institutional Collaborative Cohort Study (J-MICC Study) (2011)
  • Author(s): Morita E
  • Journal Title: Nagoya J Med Sci Volume: 73(3-4) Pages: 187-95
  • Peer Reviewed
• [Journal Article] Ammonium perfluorooctanoate may cause testosterone reduction by adverselv affecting testis in relation to PPARα (2011)
  • Author(s): Li Y
  • Journal Title: Toxicol Lett Volume: 205(3) Issue: 3 Pages: 265-72
  • DOI: 10.1016/j.toxlet.2011.06.015
  • Peer Reviewed
• [Journal Article] Hepatic peroxisome proliferator-activated receptor α may have an importantrole in the toxic effects of di(2-ethylhexyl)phthalate on offspring of mice. (2011)
  • Author(s): Hayashi Y, Ito Y, Yamagishi N, Yanagiba Y, Tamada H, Wang D, Ramdhan DH, Naito H, Harada Y, Kamijima M, Gonzales FJ, Nakajima T.
  • Journal Title: Toxicology Volume: (印刷中 未定)
  • Peer Reviewed
• [Journal Article] Differential Response to Trichloroethylene-Induced Hepatosteatosis in Wild-Type and PPARalpha-Humanized Mice. (2010)
  • Author(s): Ramdhan DH, Kamijima M, Wang D, Ito Y, Naito H, Yanagiba Y, Hayashi Y, Tanaka N, Aoyama T, Gonzalez FJ, Nakajima T.
  • Journal Title: Environmental Health Perspective Volume: 118(11) Pages: 1557-1563
  • Peer Reviewed
• [Presentation] 高脂肪食摂取による2系統ラットの線維化進展の差は各々の胆汁酸排泄の違いと関連する (2012)
  • Author(s): 内藤久雄
  • Organizer: 第82回日本衛生学会学術総会
  • Place of Presentation: 京都大学
  • Year and Date: 2012-03-25
• [Presentation] SHRSP5/Dmcrラットの脂肪摂取量と脂肪肝・肝炎・線維化との関連性 (2012)
  • Author(s): 滝仁志
  • Organizer: 第82回日本衛生学会学術総会
  • Place of Presentation: 京都大学
  • Year and Date: 2012-03-25
• [Presentation] EPAは高脂肪食による胆汁酸のグルクロン酸、硫酸抱合の低下を抑制する (2012)
  • Author(s): 賈小芳
  • Organizer: 第82回日本衛生学会学術総会
  • Place of Presentation: 京都大学
  • Year and Date: 2012-03-25
• [Presentation] SHRSP5/DmcrのNASHモデルとしての有用性と食事療法の検討 (2012)
  • Author(s): 玉田葉月
  • Organizer: 第82回日本衛生学会学術総会
  • Place of Presentation: 京都大学
  • Year and Date: 2012-03-25
• [Presentation] トリクロロエチレン曝露による免疫性肝障害に関する研究 (2012)
  • Author(s): 日比野優衣
  • Organizer: 第82回日本衛生学会学術総会
  • Place of Presentation: 京都大学
  • Year and Date: 2012-03-25
• [Presentation] 胎生期DEHP曝露による低栄養と摂食行動 (2012)
  • Author(s): 林由美
  • Organizer: 第82回日本衛生学会学術総会
  • Place of Presentation: 京都大学
  • Year and Date: 2012-03-25
• [Presentation] ヒトの出産前後における血液DEHP代謝物濃度の解析 (2012)
  • Author(s): 田川雅大
  • Organizer: 第82回日本衛生学会学術総会
  • Place of Presentation: 京都大学
  • Year and Date: 2012-03-25
• [Presentation] 2系統のラットを用いた高脂肪食による肝炎・線維化進展に関連するコレステロール・胆汁酸動態の解析 (2011)
  • Author(s): 内藤久雄
  • Organizer: 第84回日本産業衛生学会学術総会
  • Place of Presentation: 東京都立産業貿易センター浜松町館
  • Year and Date: 2011-05-18
• [Presentation] Molecular signaling of high-fat-cholesterol (HFC) diet-induced apoptosis and necrosis in relation to the liver fibrosis progression in SHRSP5/Dmcr male rats (2011)
  • Author(s): Yetti H, Naito H, Jia X, Tamada H, Kitamori K, Shindo M, Taki H, Wang J, Nakajima T
  • Organizer: 第81回 日本衛生学会学術総会
  • Place of Presentation: 昭和大学旗の台キャンパス(発表確定)
  • Year and Date: 2011-03-28
• [Presentation] Effect of EPA on KLF6 and its related gene expressions in high-fat and-cholesterol-fed SHRSP5/Dmcr rats (2011)
  • Author(s): Wang J, Naito H, Jia X, Yetti H, Tamada H, Kitamori K, Nakajima T
  • Organizer: 第81回 日本衛生学会学術総会
  • Place of Presentation: 昭和大学旗の台キャンパス(発表確定)
  • Year and Date: 2011-03-28
• [Presentation] Preventive effects of eicosapentaenoic acid supplementation on high-fat and high-cholesterol diet-induced hepatic damage in SHRSP5/Dmcr rats (2011)
  • Author(s): Jia X, Naito H, Yetti H, Tamada H, Kitamori K, Hayashi Y, Yamagishi N, Wang J, Nakajima T
  • Organizer: 第81回 日本衛生学会学術総会
  • Place of Presentation: 昭和大学旗の台キャンパス(発表確定)
  • Year and Date: 2011-03-27
• [Presentation] 高脂肪食によるコレステロール・胆汁酸の体内動態変化と肝線維化進展への影響 (2011)
  • Author(s): 内藤久雄
  • Organizer: 第81回日本衛生学会学術総会
  • Year and Date: 2011-03-26
• [Presentation] 高脂肪食によるコレステロール・胆汁酸の体内動態変化と肝線維化進展への影響 (2011)
  • Author(s): 内藤久雄, 玉田葉月, 植草良輔, 北森一哉, 柳場由絵, 王棟, 那須民江
  • Organizer: 第81回 日本衛生学会学術総会
  • Place of Presentation: 昭和大学旗の台キャンパス(発表確定)
  • Year and Date: 2011-03-26
• [Presentation] 妊娠期DEHP曝露による母獣の血漿中トリグリセライド減少メカニズム (2011)
  • Author(s): 林由美、山岸希、伊藤由起、内藤久雄、那須民江
  • Organizer: 第81回 日本衛生学会学術総会
  • Place of Presentation: 昭和大学旗の台キャンパス(発表確定)
  • Year and Date: 2011-03-26
• [Presentation] Apoptosis and necrosis in relation to liver fibrosis in SHRSP5/Dmcr rats fed high-fat-cholesterol(HFC) diet and EPA effects (2011)
  • Author(s): Yetti H
  • Organizer: 第10回分子予防環境医学研究会
  • Place of Presentation: 京都府立医科大学医学部旧図書館棟3階講堂
  • Year and Date: 2011-01-22
• [Presentation] Molecular analysis for preventive effects of eicosapentaenoic acid supplementation on high-fat and high-cholesterol diet-induced hepatic change in SHRSP5/Dmcr rats. (2011)
  • Author(s): Jia X, Naito H, Yetti H, Wang J, Tamada H, Kitamori K, Hayashi Y, Yamagishi N, Nakajima T
  • Organizer: 第10回 分子予防環境医学研究会
  • Place of Presentation: 京都府立医科大学医学部旧図書館棟3階講堂
  • Year and Date: 2011-01-22
• [Presentation] Apoptosis and necrosis in relation to liver fibrosis in SHRSP5/Dmcr rats fed high-fat-cholesterol (HFC) diet and EPA effects. (2011)
  • Author(s): Yetti H, Naito H, Jia X, Tamada H, Kitamori K, Shindo M, Taki H, Wang J, Nakajima T
  • Organizer: 第10回 分子予防環境医学研究会
  • Place of Presentation: 京都府立医科大学医学部旧図書館棟3階講堂
  • Year and Date: 2011-01-22
• [Presentation] 2系統のラットを用いた高脂肪食による肝炎・線維化進展に関連するコレステロール・胆汁酸動態の解析 (2010)
  • Author(s): 内藤久雄
  • Organizer: 平成22年度日本産業衛生学会東海地方会学会
  • Place of Presentation: 浜松医科大学
  • Year and Date: 2010-11-13
• [Presentation] トリクロロエチレン誘発性肝障害におけるPPARα活性の種差による影響について (2010)
  • Author(s): Ramdhan DH, 上島通浩, 王棟, 伊藤由起, 柳場由絵, 林由美, 内藤久雄, Gonzalez FJ, 那須民江
  • Organizer: 第83回 日本産業衛生学会
  • Place of Presentation: 福井国際交流会館
  • Year and Date: 2010-05-28
• [Presentation] 高脂肪食によるコレステロール・胆汁酸の体内動態変化と肝線維化進展への影響 (2010)
  • Author(s): 内藤久雄
  • Organizer: 第80回日本衛生学会学術総会
  • Place of Presentation: 仙台国際センター
  • Year and Date: 2010-05-11
• [Presentation] 高脂肪食によるコレステロール・胆汁酸の体内動態変化と肝線維化進展への影響 (2010)
  • Author(s): 内藤久雄, 玉田葉月, 植草良輔, 北森一哉, 柳場由絵, 王棟, 那須民江
  • Organizer: 第80回 日本衛生学会学術総会
  • Place of Presentation: 仙台国際センター
  • Year and Date: 2010-05-11
• [Presentation] EPAはHFC食によるSHRSP5/Dmcrラットの肝障害を早期において予防するかもしれない (2010)
  • Author(s): 賈小芳, 玉田葉月, 北森一哉, 内藤久雄, 山岸希, 林由美, 植草良輔, 王棟, 那須民江
  • Organizer: 第80回 日本衛生学会学術総会
  • Place of Presentation: 仙台国際センター
  • Year and Date: 2010-05-11
• [Presentation] 非アルコール性脂肪性肝炎の食事療法の効果に関する研究 (2010)
  • Author(s): 玉田葉月, 北森一哉, 内藤久雄, 林由美, 山岸希, 小林身哉, 柳場由絵, 那須民江
  • Organizer: 第80回 日本衛生学会学術総会
  • Place of Presentation: 仙台国際センター
  • Year and Date: 2010-05-11
• [Presentation] 胎生期DEHP曝露による低栄養と生活習慣病リスクとの関連 (2010)
  • Author(s): 林由美, 伊藤由起, 柳場由絵, 王棟, 山岸希, 賈小芳, 内藤久雄, 那須民江
  • Organizer: 第80回日本衛生学会学術総会
  • Place of Presentation: 仙台国際センター
  • Year and Date: 2010-05-10
• [Presentation] DEHP曝露によるPPARαの活性化で妊娠マウスの血漿中必須脂肪酸濃度が低下する (2010)
  • Author(s): 中島亮輔, 林由美, 王棟, 伊藤由起, RamdhanDoni Hikat, 内藤久雄, 上島通浩, 那須民江
  • Organizer: 第80回 日本衛生学会学術総会
  • Place of Presentation: 仙台国際センター
  • Year and Date: 2010-05-10
• [Presentation] Differential Response to High-fat and High-cholesterol Diet-induced Hepatic Fibro genesis in SHRSP5/Dmcr and SHRSP Rats (2010)
  • Author(s): Naito H
  • Organizer: The Nine JSH Single Topic Conference NASH 2010
  • Place of Presentation: Grand Prince Hotel Takanawa
• [Presentation] 高脂肪食による肝炎・繊維化進展におけるコレステロール・胆汁酸の合成・代謝・排泄に関わる核内受容体及び薬物トランスポーターの発現低下 (2010)
  • Author(s): 柳場由絵
  • Organizer: 第83回日本産業衛生学会
  • Place of Presentation: フェニックス・プラザ(福井)
• [Presentation] パーフルオロオクタン酸による肝障害とPPARalphaの関与に関する研究 (2010)
  • Author(s): 那須民江, 中川智彦, Ramdhan DH, 内藤久雄, 玉田葉月, 伊藤由起, 林由美, 山岸希, 柳場由絵
  • Organizer: 第80回 日本衛生学会学術総会
  • Place of Presentation: 仙台国際センター
• [Presentation] 高脂肪食による肝炎・繊維化進展におけるコレステロール・胆汁酸の合成・代謝・排泄に関わる核内受容体及び薬物トランスポーターの発現低下 (2010)
  • Author(s): 柳場由絵, 内藤久雄, 王棟, 那須民江
  • Organizer: 第83回 日本産業衛生学会
  • Place of Presentation: フェニックス・プラザ(福井)
• [Presentation] DI (2-ETHYLHEXYL) PHTALATE MAY CAUSE REPRODUCTIVE AND DEVELOPMENTAL TOXICITY THROUGH PPARALPHA (2010)
  • Author(s): Hayashi Y, Ito Y, Yanagiba Y, Wang D, Yamagishi N, Tamada H, Naito H, Nakajima T
  • Organizer: XII International Congress of Toxicology
  • Place of Presentation: Palau de Congressos de Barcelona (Barcelona, Spain)
• [Presentation] DIFFERENTIAL RESPONSE TO TRICHLOROETHYLENE-INDUCED HEPATOSTEATOSIS IN WILD-TYPE AND PPARA-HUMANIZED MICE (2010)
  • Author(s): Ramdhan DH, Kamijima M, Wang D, Ito Y, Yanagiba Y, Hayashi Y, Naito H, Gonzalez FJ, Nakajima T
  • Organizer: XII International Congress of Toxicology
  • Place of Presentation: Palau de Congressos de Barcelona (Barcelona, Spain)
• [Presentation] Differential Response to High-fat and High-cholesterol Diet-induced Hepatic Fibrogenesis in SHRSP5/Dmcr and SHRSP Rats. (2010)
  • Author(s): Naito H, Jia X, Tamada H, Kitamori K, Uekusa R, Yanagiba Y, Wang D, Husna Y, Yamori Y, Nakajima T
  • Organizer: The Nine JSH Single Topic Conference "NASH 2010"
  • Place of Presentation: Grand Prince Hotel Takanawa
• [Presentation] A Novel Mechanism of Eicosapentaenoic Acid Supplementation for Preventing High-fat and High-cholesterol Diet-induced Fibrosis in SHRSP5/Dmcr Rats (2010)
  • Author(s): Jia X, Naito H, Tamada H, Kitamori K, Hayashi Y, Yamagishi N, Wang D, Yetti H, Yamori Y, Nakajima T
  • Organizer: The Nine JSH Single Topic Conference "NASH 2010"
  • Place of Presentation: Grand Prince Hotel Takanawa
• [Book] Chapter title : The Toxicity of Fenitrochion and Permethrin. Book title : Insecticides/Book 1 (2012)
  • Author(s): Wang D, Naito H, Nakajima T
  • Publisher: In Tech