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New prevention strategies for non-alcoholic steatohepatitis - a study on the importance of blood pressure and nutritional management

Research Project

Project/Area Number 15H04788
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Hygiene and public health
Research InstitutionChubu University

Principal Investigator

NASU Tamie  中部大学, 生命健康科学部, 特任教授 (10020794)

Co-Investigator(Kenkyū-buntansha) 石井 晃  名古屋大学, 医学系研究科, 教授 (30252175)
内藤 久雄  藤田保健衛生大学, 医学部, 講師 (90547556)
山ノ下 理  中部大学, 生命健康科学部, 講師 (50424924)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥16,250,000 (Direct Cost: ¥12,500,000、Indirect Cost: ¥3,750,000)
Fiscal Year 2017: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2015: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
KeywordsNASH / コレステロール / 高血圧 / 降圧剤 / 線維症 / CD68 / SHR / TNFα / 非アルコール性脂肪性肝炎 / 血圧 / 高脂肪食 / 胆汁酸 / 相互作用 / ヒドララジン / 高脂肪-高コレステロール食 / 線維化 / コラーゲン / 炎症 / 予防 / Wistar-Kyoto / SHRSP5/Dmcr
Outline of Final Research Achievements

We investigated the mechanism that underlies the progression of hypertension-associated NASH by comparing differences in HFC diet-induced NASH among hypertensive SHR and SHRSP5/Dmcr, and normotensive WKY. The diet induced severe NASH in the hypertensive rats, whereas it only caused mild NASH in the normotensive rats. Increased activation of TGFβ/MAPK pathway was observed in the hypertensive rats; it suppressed nrf2 pathway in the hypertensive rats and led to lower increases in the hepatic level of HO-1. These signaling pathways might play crucial roles in the development of hypertension-associated NASH.
We also investigated whether antihypertensive drug suppress HFC-induced NASH in hypertensive SHR rats. It suppressed HFC-induced NASH in the liver of SHR rats. It significantly suppressed HFC-induced increases of inflammation- and fibrosis-related molecular markers. Thus, intervention of antihypertensive drug might be important in the prevention of NASH.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (14 results)

All 2018 2017 2016 2015

All Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 6 results,  Acknowledgement Compliant: 1 results) Presentation (8 results)

  • [Journal Article] The role of cholesterol in the pathogenesis of hypertention-associated nonalcoholic steatohepatitis2018

    • Author(s)
      Yuan Yuan、Naito Hisao、Nakajima Tamie
    • Journal Title

      InTechOpen

      Volume: -

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Bile acid detoxifying enzymes limit susceptibility to liver fibrosis in female SHRSP5/Dmcr rats fed with a high-fat-cholesterol diet2018

    • Author(s)
      Yetti Husna、Naito Hisao、Yuan Yuan、Jia Xiaofang、Hayashi Yumi、Tamada Hazuki、Kitamori Kazuya、Ikeda Katsumi、Yamori Yukio、Nakajima Tamie
    • Journal Title

      PLOS ONE

      Volume: 13 Issue: 2 Pages: e0192863-e0192863

    • DOI

      10.1371/journal.pone.0192863

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Combination of Hypertension Along with a High Fat and Cholesterol Diet Induces Severe Hepatic Inflammation in Rats via a Signaling Network Comprising NF-κB, MAPK, and Nrf2 Pathways2017

    • Author(s)
      Yuan Yuan、Naito Hisao、Jia Xiaofang、Kitamori Kazuya、Nakajima Tamie
    • Journal Title

      Nutrients

      Volume: 9 Issue: 9 Pages: 1018-1018

    • DOI

      10.3390/nu9091018

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Importance of detoxifying enzymes in differentiating fibrotic development between SHRSP5/Dmcr and SHRSP rats2016

    • Author(s)
      Hisao Naito, Xiaofang Jia, Husna Yetti, Yukie Yanagiba, Hazuki Tamada, Kazuya Kitamori, Yumi Hayashi, Dong Wang, Masashi Kato, Akira Ishii, Tamie Nakajima
    • Journal Title

      Environmental Health and Preventive Medicine

      Volume: 21 Issue: 5 Pages: 368-381

    • DOI

      10.1007/s12199-016-0539-x

    • NAID

      50012009989

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Efficacy of dietary lipid control in healing high-fat and high-cholesterol diet-induced fibrotic steatohepatitis in rats.2016

    • Author(s)
      Tamada H, Naito H, Kitamori K, Hayashi Y, Yamagishi N, Kato M, Nakajima T.
    • Journal Title

      PLoS One

      Volume: 11(1) Issue: 1 Pages: 1-17

    • DOI

      10.1371/journal.pone.0145939

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Mechanism Analysis and Prevention of Pathogenesis of Nonalcoholic Steatohepatitis2015

    • Author(s)
      那須民江、内藤久雄
    • Journal Title

      Nippon Eiseigaku Zasshi (Japanese Journal of Hygiene)

      Volume: 70 Issue: 3 Pages: 197-204

    • DOI

      10.1265/jjh.70.197

    • NAID

      130005098970

    • ISSN
      0021-5082, 1882-6482
    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 高血圧及び高脂肪食摂取はラット肝臓Cyp7a1プロモーターのメチル化頻度を増加させる2018

    • Author(s)
      内藤久雄、三宅邦夫、袁媛、橋本沙幸、北森一哉、八屋寛、那須民江
    • Organizer
      第88回日本衛生学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 降圧剤による高脂肪・高コレステロール食由来肝線維化シグナル系の抑制2018

    • Author(s)
      袁媛、内藤久雄、北森一哉、橋本沙幸、那須民江
    • Organizer
      第88回日本衛生学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 降圧剤は高脂肪・高コレステロール食で誘導される脂肪性肝炎の進行を抑える2017

    • Author(s)
      袁媛、那須民江
    • Organizer
      第87回日本衛生学会学術総会
    • Place of Presentation
      宮崎県宮崎フェニックスシーガイアリゾートシーガイアコンベンションセンター(宮崎県宮崎市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] 解毒酵素の発現抑制が食餌性由来肝線維化進展に重要である2017

    • Author(s)
      内藤久雄、那須民江
    • Organizer
      第87回日本衛生学会学術総会
    • Place of Presentation
      宮崎県宮崎フェニックスシーガイアリゾートシーガイアコンベンションセンター(宮崎県宮崎市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] 高脂肪食摂取による肝線維化進展とオートファジー・小胞体ストレス2016

    • Author(s)
      内藤久雄、那須民江
    • Organizer
      第86回日本衛生学会学術総会
    • Place of Presentation
      北海道旭川市民文化会館(北海道旭川市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] Hypertension may influence high-fat and cholesterol-induced hepatitis in rats2016

    • Author(s)
      袁媛、那須民江
    • Organizer
      第86回日本衛生学会学術総会
    • Place of Presentation
      北海道旭川市民文化会館(北海道旭川市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] 高脂肪食摂取による肝炎・線維症進展におけるオートファジーの関与2015

    • Author(s)
      内藤久雄、吉川由貴、北森一哉、那須民江
    • Organizer
      第51回高血圧関連疾患モデル学会
    • Place of Presentation
      大阪府府中市千里ライフサイエンスセンター
    • Year and Date
      2015-10-30
    • Related Report
      2015 Annual Research Report
  • [Presentation] 非アルコール性脂肪性肝疾患におけるコレステロール摂取の影響と肝臓脂肪酸組成の変化2015

    • Author(s)
      北森一哉、宮澤大介、内藤久雄、土倉覚、安井菜穂美、池田克巳、家森幸男、那須民江
    • Organizer
      第51回高血圧関連疾患モデル学会
    • Place of Presentation
      大阪府府中市千里ライフサイエンスセンター
    • Year and Date
      2015-10-30
    • Related Report
      2015 Annual Research Report

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Published: 2015-04-16   Modified: 2019-03-29  

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