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Elucidation of the organ linkage between non-alcoholic steatohepatitis and cardiovascular disease mediated by the liver X receptor

Research Project

Project/Area Number 18K10993
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 59040:Nutrition science and health science-related
Research InstitutionOkayama University

Principal Investigator

WATANABE SHOGO  岡山大学, 保健学域, 准教授 (20548341)

Co-Investigator(Kenkyū-buntansha) 林 由美  名古屋大学, 医学系研究科(保健), 講師 (30632707)
Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
KeywordsNASH / 動脈硬化 / SHRSP5 / 心筋梗塞 / 胆汁酸 / 肝臓X受容体 / 非アルコール性脂肪性肝炎
Outline of Final Research Achievements

Liver X receptor (LXR) activity is expected to have an innovative effect of extracting cholesterol from once formed atherosclerotic lesions and regressing arteriosclerosis, but it also induces a lipid synthesis system gene (SREBP1c). It has the drawback of further exacerbating hepatic lipid deposition. In this study, in order to overcome this drawback, the applicants have a special purpose (1): the inhibitory effect of bile acid on SREBP1c activity and the purpose (2): the efficacy of vabagenin, which is a novel ligand candidate for LXR activity that does not activate SREBP1c. As a result of examination using the NASH- myocardial infarction onset model (SHRSP5 / Dmcr rat), the lipid deposition in the arteries was improved without aggravating fatty liver.

Academic Significance and Societal Importance of the Research Achievements

非アルコール性脂肪性肝炎(NASH)は、大きな自覚症状がないことから長年軽視されてきた。しかしながら、NASHが肝硬変、肝がんに移行することが明らかとなったことで、積極的な治療ターゲットという認識に変わってきた。また、NASHは肝臓だけにとどまらず、メタボリックシンドロームを背景とした糖尿病、脂質異常症、高血圧を悪化させ、虚血性心疾患の発症率と死亡率を2倍以上高くすることも、予後を悪くする原因となっている。増大する医療費を削減するため、自覚症状が少ない早期のNASHのうちから、積極的な治療介入を行うことができれば、致死的な虚血性心疾患への進行を事前に食い止めることができる。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (19 results)

All 2022 2021 2020 2019 2018

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Open Access: 2 results) Presentation (12 results) (of which Int'l Joint Research: 7 results,  Invited: 1 results)

  • [Journal Article] A high-fat/high-cholesterol diet, but not high-cholesterol alone, increases free cholesterol and apoE-rich HDL serum levels in rats and upregulates hepatic ABCA1 expression2022

    • Author(s)
      Ryoko Shinohata, Misako Shibakura, Yujiro Arao, Shogo Watanabe, Satoshi Hirohata, Shinichi Usui
    • Journal Title

      Biochimie

      Volume: 197 Pages: 49-58

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Osteopontin silencing attenuates bleomycin-induced murine pulmonary fibrosis by regulating epithelial mesenchymal transition2021

    • Author(s)
      Omer Faruk Hatipoglu, Eyyup Uctepe, Gabriel Opoku, Hidenori Wake, Kentaro Ikemura, Takashi Ohtsuki, Junko Inagaki, Mehmet Gunduz, Esra Gunduz, Shogo Watanabe, Takashi Nishinaka, Hideo Takahashi, Satoshi Hirohata
    • Journal Title

      Biomedicine & Pharmacotherapy

      Volume: 139 Pages: 111633-111633

    • NAID

      120007099347

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Low plasma apolipoprotein E-rich high-density lipoprotein levels in patients with metabolic syndrome2020

    • Author(s)
      Ryoko Shinohata, Yuhei Shiga, Shin-Ichiro Miura, Satoshi Hirohata, Misako Shibakura, Tomoe Ueno-Iio, Shogo Watanabe, Yujiro Arao, Shinichi Usui
    • Journal Title

      Clinica Chimica Acta

      Volume: 510 Pages: 531-536

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Bile acids aggravate nonalcoholic steatohepatitis and cardiovascular disease in SHRSP5/Dmcr rat model2020

    • Author(s)
      Shusei Yamamoto, Ikumi Sato, Natsuki Fukuhama, Natsumi Akiyama, Miku Sakai, Shota Kumazaki, Shang Ran, Satoshi Hirohata, Kazuya Kitamori, Yukio Yamori, Shogo Watanabe
    • Journal Title

      Experimental and Molecular Pathology

      Volume: in press

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Non-alcoholic steatohepatitis aggravates nitric oxide synthase inhibition-induced arteriosclerosis in SHRSP5/Dmcr rat model2019

    • Author(s)
      S. Watanabe, S. Kumazaki, S. Yamamoto, I Sato, K. Kitamori, M. Mori, Y. Yamori, S. Hirohata
    • Journal Title

      International Journal of Experimental Pathology

      Volume: 99(6) Pages: 282-294

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Bile acid metabolism is an intermediary factor between non-alcoholic steatohepatitis and ischemic heart disease in SHRSP5/Dmcr rats2019

    • Author(s)
      Shota Kumazaki, Mayu Nakamura, Shun Sasaki, Rina Tagashira, Nozomi Maruyama, Ikumi Sato, Shusei Yamamoto, Shang Ran, Shinichi Usui, Ryoko Shinohata, Takashi Ohtsuki, Satoshi Hirohata, Kazuya Kitamori, Mari Mori, Yukio Yamori, Shogo Watanabe
    • Journal Title

      Journal of Nutrition and Food Sciences

      Volume: 9(4) Pages: 1-9

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Non-alcoholic steatohepatitis aggravates nitric oxide synthase inhibition-induced arteriosclerosis in SHRSP5/Dmcr rat model2018

    • Author(s)
      Watanabe Shogo、Kumazaki Shota、Yamamoto Shusei、Sato Ikumi、Kitamori Kazuya、Mori Mari、Yamori Yukio、Hirohata Satoshi
    • Journal Title

      International Journal of Experimental Pathology

      Volume: 99 Issue: 6 Pages: 282-294

    • DOI

      10.1111/iep.12301

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Effect of Elevated Uric Acid by Fructose Overload on NASH and Atherosclerosis2021

    • Author(s)
      Fujii Moe, Watanabe Shogo
    • Organizer
      ICoLa 2021
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Antioxidant Action of Xanthine Oxidase Inhibitor Febuxostat Protects Liver and Blood Vascular System2021

    • Author(s)
      Kakimoto Mai, Watanabe Shogo
    • Organizer
      ICoLa 2021
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] OBETICHOLIC ACID AMELIORATES NON-ALCOHOLIC STEATOHEPATITIS AND ATHEROSCLEROSIS IN SHRSP5/DMCR RATS2020

    • Author(s)
      Ikumi Sato, Shogo Watanabe etc
    • Organizer
      88th EAS
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] THE NOVEL LIVER X RECEPTOR BETA AGONIST, OUABAGENIN, PREVENT ARTERIAL LIPID DEPOSITION IN SHRSP5/DMCR RAT2020

    • Author(s)
      Shusei Yamamoto, Shogo Watanabe etc
    • Organizer
      88th EAS
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] 新規LXRβアゴニストであるウアバゲニンを用いた動脈脂質沈着に対する改善効果の検討2020

    • Author(s)
      山元修成、渡辺彰吾 他
    • Organizer
      第52回日本動脈硬化学会
    • Related Report
      2020 Research-status Report
  • [Presentation] 非アルコール性脂肪肝炎と心血管疾患を 増悪させる仲介因子としての胆汁酸の役割2019

    • Author(s)
      佐藤 生弥、山元 修成、熊崎 章太、福濱 那月、秋山 菜摘、酒井 美玖、 Shang Ran、廣畑 聡、渡辺 彰吾
    • Organizer
      日本動脈硬化学会
    • Related Report
      2019 Research-status Report
  • [Presentation] Bile acid metabolism mediates between nonalcoholic steatohepatitis and cardiovascular disease2019

    • Author(s)
      Shusei Yamamoto, Ikumi Satoh, Natsumi Akiyama, Miku Sakai, Natsuki Fukuhama, Shang Ran, Satoshi Hirohata, Shogo Watanabe
    • Organizer
      ICoLA2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Bile acids aggravate non-alcoholic steatohepatitis and cardiovascular disease in SHRSP5/Dmcr2019

    • Author(s)
      Ikumi Satoh, Shusei Yamamoto, Natsuki Fukuhama, Natsumi Akiyama, Miku Sakai, Shota Kumazaki, Satoshi Hirohata, Shogo Watanabe
    • Organizer
      ICoLA2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 非アルコール性脂肪肝炎において心血管疾患を増悪する仲介因子となり得る胆汁酸代謝2019

    • Author(s)
      山元 修成, 佐藤 生弥,熊崎 章太,秋山 菜摘,酒井 美玖,福濱 那月, Shang Ran,廣畑 聡,渡邊 彰吾
    • Organizer
      SHR等疾患モデル研究会
    • Related Report
      2019 Research-status Report
  • [Presentation] Non-alcoholic steatohepatitis aggravates myocardial infarction induced by NO synthase inhibitor2018

    • Author(s)
      Shogo watanabe et al
    • Organizer
      SHR symposium 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] SHRSP5/Dmcrラットを用いた非アルコール性脂肪性肝炎と心血管傷害の仲介因子としての胆汁酸代謝2018

    • Author(s)
      渡辺彰吾 他
    • Organizer
      第50回日本動脈硬化学会総会・学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 脳梗塞易発性高血圧自然発症(SHRSP)ラットの新規亜系統として注目されるSHRSP5/Dmcrモデルの基礎病態2018

    • Author(s)
      渡辺彰吾
    • Organizer
      第50回日本動脈硬化学会総会・学術集会
    • Related Report
      2018 Research-status Report
    • Invited

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Published: 2018-04-23   Modified: 2023-01-30  

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