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Analysis of mechanisms for NASH pathogenesis associated with endotoxin-induced dysorder of lipid metabolism

Research Project

Project/Area Number 25860550
Research Category

Grant-in-Aid for Young Scientists (B)

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

Principal Investigator

IMAJO kento  横浜市立大学, 附属病院, 助教 (30600192)

Research Collaborator NAKAJIMA Atsushi  横浜市立大学, 医学研究科, 教授 (30326037)
SAITO Satoru  横浜市立大学, 医学部, 准教授 (00275041)
OGAWA Yuji  横浜市立大学, 附属病院, 指導診療医 (20644959)
Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords非アルコール性脂肪肝炎 / NASH / 病態進展機序の解明 / エンドトキシン / 脂質代謝 / NASH病態進展機序 / 遊離脂肪酸 / 炎症性サイトカイン / MTP
Outline of Final Research Achievements

Gut derived endotoxin (ET) is the one of the major pathogenesis of the development of nonalcoholic steatohepatitis (NASH). We have recently demonstrated the hyper responsibility to ET in the fatty liver by increasing the expression of CD14 which is the co-receptor for ET by increase in leptin, promoting the chronic steatohepatitis even under the low-dose ET exposure in high-fat diet (HFD)-fed obese mice. However, to investigate the role of ET in human NASH pathogenesis, we must use lower dose of ET, which does not lead to liver disorder, even in HFD-fed obese mice. In this research, we found that the very low dose ET decreased hepatic microsomal triglyceride transfer protein (MTTP), key factor of lipid metabolism, led to excess accumulation of free fatty acid (FFA), result in development of NASH pathogenesis, even advanced liver fibrosis.

Report

(3 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (9 results)

All 2014 2013 Other

All Journal Article (4 results) (of which Peer Reviewed: 3 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (5 results) (of which Invited: 2 results)

  • [Journal Article] LDL-migration index (LDL-MI), an indicator of small dense low-density lipoprotein (sdLDL), is higher in non-alcoholic steatohepatitis than in non-alcoholic fatty liver: a multicenter cross-sectional study.2014

    • Author(s)
      Imajo K, Hyogo H, Yoneda M, Honda Y, Kessoku T, Tomeno W, Ogawa Y, Taguri M, Mawatari H, Nozaki Y, Fujita K, Kirikoshi H, Saito S, Sumida Y, Ono M, Wada K, Nakajima A, Eguchi Y.
    • Journal Title

      PLoS One

      Volume: 26;9(12) Issue: 1

    • DOI

      10.1186/s12876-015-0269-3

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Microbiota and nonalcoholic steatohepatitis.2014

    • Author(s)
      Imajo K, Yoneda M, Ogawa Y, Wada K, Nakajima A.
    • Journal Title

      Semin Immunopathol.

      Volume: 36(1) Pages: 115-132

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Rodent models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis.2013

    • Author(s)
      Imajo K, Yoneda M, Kessoku T, Ogawa Y, Maeda S, Sumida Y, Hyogo H, Eguchi Y, Wada K, Nakajima A.
    • Journal Title

      Int J Mol Sci.

      Volume: 4; 14(11) Pages: 21833-21857

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] NASHの成因と病態.(3) NASH病態とレプチン2013

    • Author(s)
      今城健人、米田正人、結束貴臣、小川祐二、中島淳
    • Journal Title

      臨床消化器内科

      Volume: 28(4) Pages: 441-446

    • Related Report
      2013 Research-status Report
  • [Presentation] A very low-dose endotoxin induced development of steatohepatitis in high-fat diet fed mice through disorder of lipid metabolism2014

    • Author(s)
      Kento Imajo、Satoru Saito、Atsushi Nakajima
    • Organizer
      2014年JDDW
    • Place of Presentation
      神戸国際展示場(兵庫県神戸市)
    • Year and Date
      2014-10-24
    • Related Report
      2014 Annual Research Report
  • [Presentation] 微量エンドトキシンは肝MTTP抑制による脂質排泄障害を介して脂肪肝炎病態進展に関与する2014

    • Author(s)
      今城 健人、小川 祐二、中島 淳
    • Organizer
      第100回日本消化器病学会総会
    • Place of Presentation
      東京国際フォーラム(東京都千代田区)
    • Year and Date
      2014-04-24
    • Related Report
      2014 Annual Research Report
  • [Presentation] 微量エンドトキシンは肝MTTP抑制による脂質排泄障害を介して脂肪肝炎病態進展に関与する

    • Author(s)
      今城健人、小川祐二、中島淳
    • Organizer
      第100回日本消化器病学会総会S8-14
    • Place of Presentation
      東京国際フォーラム Dブロック 5階 ホールD5(東京都千代田区)
    • Related Report
      2013 Research-status Report
  • [Presentation] 肥満はレプチンを介して肝臓におけるエンドトキシン感受性を亢進させることにより脂肪肝炎病態進展に関与する

    • Author(s)
      今城 健人、米田 正人、中島 淳
    • Organizer
      第50回日本消化器免疫学会総会
    • Place of Presentation
      ホテルグランドヒル市ヶ谷(東京都新宿区)
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 脂肪性肝炎における肥満誘導性エンドトキシン感受性亢進機序の解明

    • Author(s)
      今城 健人、中島 淳
    • Organizer
      第10回宮崎サイエンスキャンプ
    • Place of Presentation
      宮崎シーガイアコンベンションセンター(宮崎県宮崎市)
    • Related Report
      2013 Research-status Report
    • Invited

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Published: 2014-07-25   Modified: 2019-07-29  

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