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

• Project/Area Number: 25462011
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Tohoku 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: ¥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)
• Keywords: NASH / 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.

Research Products

• [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
  • 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
• [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
  • 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
• [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
• [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
  • 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
• [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
  • 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
• [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
• [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
• [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
• [Presentation] The effectiveness of duodeno-jejunal bypass for nonalcoholic steatohepatitis (NASH) in diet-induced rat model of NASH (2014)
  • 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
• [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