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Elucidation of mechanisms related to toxicity and susceptibility of various fatty acids in NASH pathology

Research Project

Project/Area Number 15K19340
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Gastroenterology
Research InstitutionYokohama City University

Principal Investigator

OGAWA Yuji  横浜市立大学, 医学部, 助教 (20644959)

Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywordslipotoxicity / NAFLD / NASH / palmitate / saturated fatty acid / 飽和脂肪酸 / NAFLD/NASH
Outline of Final Research Achievements

In this study, after palmitate-injection, basal diet (BD)-fed mice did not altered the serum ALT, but high fat diet (HFD)-fed mice exhibited increased the serum ALT. Very low dose lipopolysaccharide (LPS)-injection increased the plasma endotoxin on BD-fed mice as same as HFD-fed mice. Both palmitate and very low dose LPS increased ALT on BD-fed mice. On BD-fed mice, palmitate induced inflammatory cells infiltration due to chemokines without ALT elevation and induced mild liver fibrosis via toll like receptor 4 (TLR4) pathway.
Collectively, palmitate alone induced inflammatory cells infiltration and mild liver fibrosis without ALT elevation. Furthermore, palmitate exacerbated NAFLD pathogenesis by cooperative interaction with gut-derived endotoxin. Our results indicate that serum palmitate and plasma gut-derived endotoxin reduction are important for NAFLD treatment.

Report

(3 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • Research Products

    (17 results)

All 2017 2016 2015

All Journal Article (4 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 3 results,  Open Access: 3 results,  Acknowledgement Compliant: 2 results) Presentation (11 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results) Book (2 results)

  • [Journal Article] Pemafibrate, a novel selective peroxisome proliferator-activated receptor alpha modulator, improves the pathogenesis in a rodent model of nonalcoholic steatohepatitis.2017

    • Author(s)
      Honda Y, Kessoku T, Ogawa Y, Tomeno W, Imajo K, Fujita K, Yoneda M, Takizawa T, Saito S, Nagashima Y, Nakajima A.
    • Journal Title

      Sci Rep.

      Volume: 7 Issue: 1 Pages: 42477-42477

    • DOI

      10.1038/srep42477

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] The characteristics of non-obese NAFLD: Effect of genetic and environmental factors.2016

    • Author(s)
      Honda Y, Yoneda M, Kessoku T, Ogawa Y, Tomeno W, Imajo K, Mawatari H, Fujita K, Hyogo H, Ueno T, Chayama K, Saito S, Nakajima A, Hotta K
    • Journal Title

      Hepatol Res

      Volume: - Issue: 10 Pages: 636-636

    • DOI

      10.1111/hepr.12648

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Resveratrol ameliorates fibrosis and inflammation in a mouse model of nonalcoholic steatohepatitis.2016

    • Author(s)
      Kessoku T, Imajo K, Honda Y, et al.
    • Journal Title

      Sci Rep

      Volume: 25 Issue: 1 Pages: 22251-22251

    • DOI

      10.1038/srep22251

    • NAID

      120005749754

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] 非アルコール性脂肪肝炎における腸内細菌由来エンドトキシンへの過剰応答性.2015

    • Author(s)
      小川祐二,本多靖,結束貴臣,今城健人,中島淳
    • Journal Title

      消化と吸収 日本消化吸収学会雑誌

      Volume: 37 Pages: 83-87

    • Related Report
      2015 Research-status Report
  • [Presentation] M2BPGiによるNAFLDの肝線維化ステージ診断における有用性2017

    • Author(s)
      小川祐二,本多靖,結束貴臣,留野渉,今城健人,米田正人,斉藤聡,中島淳
    • Organizer
      第四回 神奈川県肝線維化マーカーM2BPGi研究会
    • Place of Presentation
      ホテル横浜キャメロットジャパン(神奈川県横浜市)
    • Year and Date
      2017-03-04
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] M2BPGiによるNAFLDの肝線維ステージ診断に関する検討2017

    • Author(s)
      小川祐二,本多靖,結束貴臣,留野渉,今城健人,米田正人,斉藤聡,中島淳
    • Organizer
      第36回アルコール医学生物学研究会学術集会
    • Place of Presentation
      新横浜プリンスホテル(神奈川県横浜市)
    • Year and Date
      2017-01-28
    • Related Report
      2016 Annual Research Report
  • [Presentation] RNAシークエンスを用いたNAFLDの肝線維化に関する解析2017

    • Author(s)
      小川祐二,本多靖,結束貴臣,留野渉,今城健人,米田正人,斉藤聡,中島淳
    • Organizer
      第36回アルコール医学生物学研究会学術集会
    • Place of Presentation
      新横浜プリンスホテル(神奈川県横浜市)
    • Year and Date
      2017-01-27
    • Related Report
      2016 Annual Research Report
  • [Presentation] 非ウイルス性肝癌症例における肝硬度および肝内鉄沈着に関する検討2016

    • Author(s)
      小川祐二,今城健人,中島淳
    • Organizer
      第41回日本肝臓学会東部会
    • Place of Presentation
      京王プラザホテル(東京都新宿区)
    • Year and Date
      2016-12-08
    • Related Report
      2016 Annual Research Report
  • [Presentation] 肥満に伴うendotoxiaが引き起こす肝臓におけるlipotocity増悪の機序解明についての検討2016

    • Author(s)
      小川祐二,本多靖,結束貴臣,留野渉,加藤真吾,今城健人,米田正人,兵庫秀幸,角田圭雄,中島淳
    • Organizer
      第3回肝臓と糖尿病・代謝研究会
    • Place of Presentation
      石川県立音楽堂邦楽ホール・交流ホール(石川県金沢市)
    • Year and Date
      2016-07-16
    • Related Report
      2016 Annual Research Report
  • [Presentation] パルミチン酸が引き起こす肝臓における自然免疫応答と肥満に伴うendotoxiaの相互作用についての検討2016

    • Author(s)
      小川祐二,本多靖,結束貴臣,加藤真吾,今城健人,米田正人,中島淳
    • Organizer
      第23回 肝細胞研究会
    • Place of Presentation
      大阪大学中之島センター (大阪府大阪市)
    • Year and Date
      2016-07-08
    • Related Report
      2016 Annual Research Report
  • [Presentation] Saturated fatty acid, palmitate, induced liver inflammation and fibrosis in vivo.2016

    • Author(s)
      Yuji Ogawa, Yasushi Honda, Takaomi Kessoku, Wataru Tomeno, Shingo Kato, Kento Imajo, Hironori Mawatari, Koji Hujita, Masato Yoneda, Satoru Saito, Atsushi Nakajima
    • Organizer
      The international liver congress 2016
    • Place of Presentation
      Fira Barcelona Gran Via(Barcerona, Spain)
    • Year and Date
      2016-04-16
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] パルミチン酸単独が引き起こすNAFLD/NASH病態における肝臓での炎症細胞浸潤と繊維化についての検討.2015

    • Author(s)
      小川祐二
    • Organizer
      第29回肝類洞壁細胞研究会学術集会 セッション4「NASH/NAFLD」
    • Place of Presentation
      秋田市にぎわい交流館(秋田県秋田市)
    • Year and Date
      2015-11-01
    • Related Report
      2015 Research-status Report
  • [Presentation] Obesity exacerbates lipotoxicity induced by saturated fatty acid.2015

    • Author(s)
      Ogawa Yuji
    • Organizer
      2015年度日本消化器関連学会週間(JDDW 2015)(第19回 日本肝臓学会)International Session(Workshop)2(JSH・JSGE)New trends in diabetes mellitus and liver diseases
    • Place of Presentation
      グランドプリンスホテル高輪(東京都品川区)
    • Year and Date
      2015-10-09
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] パルミチン酸単独投与による自然免疫応答を介した肝線維化についての検討.2015

    • Author(s)
      小川祐二
    • Organizer
      第51回日本肝臓学会総会 セッション42  NAFLD・基礎1
    • Place of Presentation
      同仁堂(熊本県熊本市)
    • Year and Date
      2015-05-21
    • Related Report
      2015 Research-status Report
  • [Presentation] パルミチン酸単独投与による自然免疫を介した肝臓における炎症細胞浸潤と線維化についての検討2015

    • Author(s)
      小川祐二
    • Organizer
      第101回日本消化器病学会総会 ワークショップ12 消化器疾患における自然免疫と制御
    • Place of Presentation
      仙台国際センター(宮城県仙台市)
    • Year and Date
      2015-04-25
    • Related Report
      2015 Research-status Report
  • [Book] 肝臓における脂肪毒性2016

    • Author(s)
      小川祐二,本多靖,結束貴臣,今城健人,留野渉,米田正人,斉藤聡,中島淳
    • Publisher
      メディカルレビュー
    • Related Report
      2016 Annual Research Report
  • [Book] Mebio2016

    • Author(s)
      小川祐二
    • Total Pages
      10
    • Publisher
      メジカルビュー社
    • Related Report
      2015 Research-status Report

URL: 

Published: 2015-04-16   Modified: 2018-03-22  

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