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The effect of hepatokine LECT2 on the pathphysiology of NASH

Research Project

Project/Area Number 16K19533
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Metabolomics
Research InstitutionKanazawa University

Principal Investigator

Kosuke Shima  金沢大学, 医学系, 協力研究員 (20770613)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords非アルコール性脂肪肝 / LECT2 / ヘパトカイン / 非アルコール性脂肪肝炎 / 糖尿病 / 栄養学
Outline of Final Research Achievements

As in the planed study design, a steatohepatitis model was created by administering CDAHFD (choline deficiency, methionine loss, containing 30% fat) to LECT2 deficient (KO) mice and LECT2 overexpressing (Tg) mice and compared with wild-type mice. Induction of steatohepatitis in LECT2 Tg mice significantly increased IL-6 expression in the liver compared to wild type, but did not significantly differ in TNF-a, MCP-1, F4 / 80, TGFb1. Hydroxyproline levels, which reflect liver fibrosis, were also elevated in Lect2 Tg mice, however there was no statistically significant difference. In Lect2 mice, there was no significant change in fibrotic inflammation-related genes, and contrary to the hypothesis, hepatic triglyceride was significantly elevated.

Academic Significance and Societal Importance of the Research Achievements

本検討では、当初の仮説と異なり、肥満で誘導されるヘパトカインであるLect2は肝臓自身には強く作用せず、脂肪肝の病態に影響を及ぼすものではなかった。非アルコール性脂肪肝炎が形成される病態は複雑であり、多数の因子が関与していると考えられる。Lect2以外のヘパトカインがオートクラインパラクライン的に肝臓に作用する可能性もあり、今後の検討が待たれる。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (14 results)

All 2018 2017 2016

All Journal Article (6 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 5 results,  Open Access: 4 results,  Acknowledgement Compliant: 1 results) Presentation (8 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Heterogeneous nature of diabetes in a family with a gain-of-function mutation in the ATP-binding cassette subfamily C member 8 (ABCC8) gene2018

    • Author(s)
      Kosuke Robert Shima, Rika Usuda, Takeshi Futatani, Hiroshi Akahori, Shuichi Kaneko, Tohru Yorifuji, and Toshinari Takamura
    • Journal Title

      Endocrine Journal

      Volume: 65 Issue: 10 Pages: 1055-1059

    • DOI

      10.1507/endocrj.EJ18-0054

    • NAID

      130007501408

    • ISSN
      0918-8959, 1348-4540
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ursodeoxycholic acid potentiates dipeptidyl peptidase-4 inhibitor sitagliptin by enhancing glucagon-like peptide-1 secretion in patients with type 2 diabetes and chronic liver disease: a pilot randomized controlled and add-on study2018

    • Author(s)
      K. R. Shima, T. Ota, K. I. Kato, Y. Takeshita, H. Misu, S. Kaneko and T. Takamura
    • Journal Title

      BMJ Open Diabetes Res Care

      Volume: 6 Issue: 1 Pages: e000469-e000469

    • DOI

      10.1136/bmjdrc-2017-000469

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Rationale and design of a multicenter placebo-controlled double-blind randomized trial to evaluate the effect of empagliflozin on endothelial function: the EMBLEM trial.2017

    • Author(s)
      Tanaka A, Shimabukuro M, Okada Y, Taguchi I, Yamaoka-Tojo M, Tomiyama H, Teragawa H, Sugiyama S, Yoshida H, Sato Y, Kawaguchi A, Ikehara Y, Machii N, Maruhashi T, Shima KR, Takamura T, Matsuzawa Y, Kimura K, Sakuma M, Oyama JI, Inoue T, Higashi Y, Ueda S, Node K; EMBLEM Trial Investigators.
    • Journal Title

      Cardiovasc Diabetol.

      Volume: 印刷中 Issue: 1 Pages: 48-48

    • DOI

      10.1186/s12933-017-0532-8

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Role of GPR40 for fish oil PUFA-mediated BDNF synthesis in the monkey hippocampus2016

    • Author(s)
      Arumugam Mathivanan, Yoshio Minabe, Tsuguhito Ota, Naoto Nagata, Kosuke R. Shima, Tetsumori Yamashima
    • Journal Title

      J Alzheimers Dis Parkinsonism

      Volume: 6 Issue: 01 Pages: 1-12

    • DOI

      10.4172/2161-0460.1000213

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Why is hippocampal CA1 especially vulnerable to Ischemia?2016

    • Author(s)
      Hanbai Liang, Shota Kurimoto, Kosuke R Shima, Daiki Shimizu, Tsuguhito Ota, Yoshio Minabe, Tetsumori Yamashima
    • Journal Title

      SOJ Biochemistry

      Volume: 2 Issue: 1 Pages: 1-7

    • DOI

      10.15226/2376-4589/2/1/00108

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 元気の出る糖尿病チームのつくり方2016

    • Author(s)
      島 孝佑、篁 俊成
    • Journal Title

      糖尿病診療マスター

      Volume: 2 Pages: 121-121

    • Related Report
      2016 Research-status Report
  • [Presentation] ウルソデオキシコール酸の単独・DPP4阻害薬との併用療法が慢性肝疾患合併2型糖尿病の体重、血糖、インクレチン分泌に及ぼす効果2018

    • Author(s)
      島 孝佑、太田嗣人、竹下有美枝、御簾博文、金子周一、篁 俊成
    • Organizer
      第5回肝臓と糖尿病・代謝研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] The effect of ursodeoxycholic acid added to dipeptidyl peptidase-4 inhibitor on GLP-1 secretion and glucose tolerance in subjects with type 2 diabetes.2017

    • Author(s)
      Kosuke R Shima, Yumie Takeshita, Hirofumi Misu, Tsuguhito Ota, Toshinari Takamura
    • Organizer
      Keystone symposia Bile Acid Receptors as Signal Integrators in Liver and Metabolism
    • Place of Presentation
      Montrey, CA, US
    • Year and Date
      2017-03-08
    • Related Report
      2016 Research-status Report
  • [Presentation] The effect of ursodeoxycholic acid added to dipeptidyl peptidase-4 inhibitor on GLP-1 secretion and glucose tolerance in subjects with type 2 diabetes.2017

    • Author(s)
      Kosuke R Shima, Yumie Takeshita, Hirofumi Misu, Tsuguhito Ota, Toshinari Takamura
    • Organizer
      77th Scientific Sessions of the American Diabetes Association
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 骨髄癌腫症に至った治療抵抗性 悪性パラガングリオーマの一剖検例2017

    • Author(s)
      島 孝佑、迫 佐央理、御簾博文、篁 俊成
    • Organizer
      第27回臨床内分泌代謝Update
    • Related Report
      2017 Research-status Report
  • [Presentation] Comparison of acarbose versus voglibose monotherapy on GLP-1 secretion and postprandial dyslipidemia in patients with type 2 diabetes2017

    • Author(s)
      Kosuke R SHIMA, Rika USUDA, Yinhua NI, Shuichi KANEKO, Toshinari TAKAMURA, Tsuguhito OTA
    • Organizer
      International Diabetes Federation 2017 Congress
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Comparison of acarbose monotherapy and voglibose monotherapy on incretin secretion and postprandial dyslipidemia in patients with type 2 diabetes: a randomized controlled study2016

    • Author(s)
      KOSUKE R SHIMA, RIKA USUDA, YINHUA NI, SHUICHI KANEKO, TOSHINARI TAKAMURA, TSUGUHITO OTA
    • Organizer
      11th IDF-WPR congress 2016 and AASD scientific meeting
    • Place of Presentation
      Taipei
    • Year and Date
      2016-10-26
    • Related Report
      2016 Research-status Report
  • [Presentation] 胆汁酸の単独・DPP4阻害薬との併用療法が2型糖尿病の体重、血糖、インクレチン分泌に及ぼす効果2016

    • Author(s)
      島 孝佑、竹下有美枝、御簾博文、篁 俊成
    • Organizer
      第37回 日本肥満学会
    • Place of Presentation
      東京
    • Year and Date
      2016-10-08
    • Related Report
      2016 Research-status Report
  • [Presentation] 2型糖尿病患者に対するウルソデオキシコール酸及びDPP-4阻害薬の単独・併用が血糖コントロールと活性型GLP-1値に及ぼす効果2016

    • Author(s)
      島 孝佑、竹下有美枝、圓山泰史、御簾博文、篁 俊成
    • Organizer
      第59回 糖尿病学会年次学術総会
    • Place of Presentation
      京都
    • Year and Date
      2016-05-18
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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