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Duodenal jejunal bypass improves non-alcoholic steatohepatitis (NASH) in diet induced NASH model rats

Research Project

Project/Area Number 25462011
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Digestive surgery
Research InstitutionTohoku University

Principal Investigator

Naitoh Takeshi  東北大学, 医学(系)研究科(研究院), 准教授 (50291258)

Co-Investigator(Kenkyū-buntansha) Shibata Chikashi  東北医科薬科大学, 医学部, 教授 (30270804)
Tanaka Naoki  東北大学, 大学病院, 助教 (60547404)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
KeywordsNASH / 減量手術 / 胆汁酸 / SREBP / FXR / 十二指腸空腸バイパス術 / Metabolic Surgery / 非アルコール性脂肪肝炎 / 肥満 / Bariatric surgery / SREBP-1c / Duodeno-Jejunal bypass / HCC
Outline of Final Research Achievements

We previously developed diet-induced NASH rat model. In this model, we performed the duodena-jejunal bypass (DJB) as a metabolic surgery and confirmed that NASH of the rat was improved dramatically. In the DJB group, the serum bile acids were elevated and expression of FXR, which is the nuclear receptor of the bile acids, was up-regulated in the liver. FXR is known to regulate the expression of the several enzymes related to metabolism, such as gluconeogenesis or lipogenesis. SREBP1c regulates the expression of the lipogenic enzymes and it is regulated by FXR as well. In this model, the level of SREBP was down-regulated in the DJB model, but not reached to the significant level comparing to the control group. However, we can conclude that NASH can be improved by the DJB and bile acids elevation and following cascade is strongly related to this mechanism.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (14 results)

All 2016 2015 2014

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

  • [Journal Article] Biliopancreatic limb plays an important role in metabolic improvement after duodenal-jejunal bypass in a rat model of diabetes.2016

    • Author(s)
      Miyachi T, Nagao M, Tanaka N, Naitoh T et al
    • Journal Title

      Surgery

      Volume: 159 Issue: 5 Pages: 1360-1371

    • DOI

      10.1016/j.surg.2015.11.027

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] 肥満症外科治療の現状と展望 肥満症外科治療の基礎 効果メカニズム.2015

    • Author(s)
      土屋堯裕, 内藤 剛, 海野倫明
    • Journal Title

      肥満研究

      Volume: 21 Pages: 27-35

    • Related Report
      2015 Annual Research Report
  • [Presentation] s Sleeve Bypass as a Metabolic Surgery Really Necessary for Japanese Obese DM patient?2016

    • Author(s)
      Naitoh T, Tanaka N, Imoto H, Tsuchiya T, Nagao M, Musha H, Ohnuma S, Morikawa T, Motoi F, Unno M
    • Organizer
      Society of Laparoscopic Surgery Asia-American Multispecialty Summit 2016
    • Place of Presentation
      Honolulu, USA
    • Year and Date
      2016-02-17
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] スリーブバイパス術の糖尿病改善効果と今後の方向性.2015

    • Author(s)
      内藤 剛, 田中直樹, 長尾宗紀, 渡辺和宏, 井本博文, 宮地智洋, 土屋堯裕, 大沼 忍, 阿部友哉, 武者宏昭, 森川孝則, 林 洋毅, 中川 圭, 元井冬彦, 海野倫明.
    • Organizer
      第28回日本内視鏡外科学会総会
    • Place of Presentation
      大阪、大阪国際会議場他
    • Year and Date
      2015-12-10
    • Related Report
      2015 Annual Research Report
  • [Presentation] 十二指腸空腸バイパス手術後ラットにおける血中胆汁酸上昇とNASH改善効果の検討.2015

    • Author(s)
      土屋堯裕, 長尾宗紀, 田中直樹, 渡辺和宏, 宮地智洋, 河野えみ子, 小野智之, 林 洋毅, 坂田直昭, 大沼 忍, 森川孝則, 中川 圭, 武者宏昭, 元井冬彦, 内藤 剛, 海野倫明.
    • Organizer
      第57回日本消化器病学会大会
    • Place of Presentation
      東京、グランドプリンスホテル新高輪他
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
  • [Presentation] Mechanism of anti-diabetic effect of the metabolic surgery.2015

    • Author(s)
      Naitoh T, Tanaka N, Nagao M, Imoto H, Miyachi T, Tsuchiya T, Kono E, Unno M.
    • Organizer
      The 8th Asia-Oceania Conference on Obesity
    • Place of Presentation
      Nagoya, 名古屋国際会議場
    • Year and Date
      2015-10-02
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 十二指腸空腸バイパス手術後ラットにおける血中胆汁酸上昇とNASH改善効果の検討.2015

    • Author(s)
      土屋堯裕, 元井冬彦, 内藤 剛, 海野倫明.
    • Organizer
      第51回日本胆道学会学術集会
    • Place of Presentation
      宇都宮、ホテル東日本宇都宮
    • Year and Date
      2015-09-17
    • Related Report
      2015 Annual Research Report
  • [Presentation] Duodenal-jejunal bypass improves non-alcoholic steatohepatitis (NASH) in a diet-induced rat model.2015

    • Author(s)
      Tsuchiya T, Nagao M, Tanaka N, Imoto H, Miyachi T, Kono E, Musha H, Motoi F, Naitoh T, Unno M.
    • Organizer
      20th World Congress of International Federation for the Surgery of Obesity & Metabolic disorders
    • Place of Presentation
      Vienna, Austria
    • Year and Date
      2015-08-26
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 十二指腸空腸バイパスにおけるbiliopancreatic limbの機能:Metabolic surgeryの機序解明にむけた新知見.2015

    • Author(s)
      宮地智洋, 内藤 剛, 長尾宗紀, 田中直樹, 渡辺和宏, 土屋堯裕, 河野えみ子, 元井冬彦, 片寄 友, 海野倫明.
    • Organizer
      第70回日本消化器外科学会総会
    • Place of Presentation
      浜松、アクトシティ浜松他
    • Year and Date
      2015-07-15
    • Related Report
      2015 Annual Research Report
  • [Presentation] 糖尿病合併重症肥満患者に対するスリーブバイパス術の効果.2015

    • Author(s)
      内藤 剛, 田中直樹, 宮地智洋, 井本博文, 土屋堯裕, 河野えみ子, 長尾宗紀, 武者宏昭, 中川 圭, 森川孝則, 元井冬彦, 片寄 友, 海野 倫明.
    • Organizer
      第52回日本外科代謝栄養学会学術集会
    • Place of Presentation
      東京、品川区民会館きゅりあん
    • Year and Date
      2015-07-02
    • Related Report
      2015 Annual Research Report
  • [Presentation] Metabolic Surgeryの作用機序ー基礎的実験の結果からー.2015

    • Author(s)
      内藤 剛, 生澤史江, 井本博文, 宮地智洋, 土屋堯裕, 河野えみ子, 田中直樹, 長尾宗紀, 海野倫明.
    • Organizer
      第33回日本肥満症治療学会学術集会
    • Place of Presentation
      幕張、幕張国際研修センター
    • Year and Date
      2015-06-26
    • Related Report
      2015 Annual Research Report
  • [Presentation] 食事誘発性NASHモデルラットにおける十二指腸空腸バイパス手術のNASH改善効果の検討2015

    • Author(s)
      土屋堯裕、長尾宗紀、田中直樹、渡辺和宏、宮地智洋、河野えみ子、小野智之、岡田恭穂、林 洋毅、坂田直昭、大沼 忍、森川孝則、中川 圭、武者宏昭、吉田 寛、元井冬彦、片寄 友、内藤 剛、海野倫明
    • Organizer
      第101回日本消化器病学会総会
    • Place of Presentation
      仙台、仙台国際センター
    • Year and Date
      2015-04-23 – 2015-04-25
    • Related Report
      2014 Research-status Report
  • [Presentation] The effectiveness of duodeno-jejunal bypass for nonalcoholic steatohepatitis (NASH) in diet-induced rat model of NASH2014

    • Author(s)
      Takahiro Tsuchiya, Munenori Nagao, Naoki Tanaka, Hiroyuki Sasaki, Tomohiro Miyachi,, Emiko Kono, Akihiro Musha, Takanori Morikawa, Tomoya Abe, Shinobu Ohnuma, Katsuyoshi Kudo, Hideaki Karasawa, Takeshi Aoki, Kei Nakagawa, Hiroshi Yoshida, Fuyuhiko Motoi, Yu Katayose, Takeshi Naitoh, Michiaki Unno
    • Organizer
      International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO) World Congress 2014
    • Place of Presentation
      Monreal, Canada
    • Year and Date
      2014-08-27 – 2014-08-30
    • Related Report
      2014 Research-status Report
  • [Book] 門脇 孝編, 糖尿病学 2015 第1版2015

    • Author(s)
      宮地智洋, 内藤 剛, 田中直樹, 海野倫明.
    • Total Pages
      168
    • Publisher
      診断と治療社
    • Related Report
      2015 Annual Research Report

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

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