Effects of metabolic surgery on improving NASH: Impact of bypassed jejunum related to the oxidative stress

• Project/Area Number: 17K10619
• 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: Naoki Tanaka 東北大学, 大学病院, 講師 (60547404)
• Co-Investigator(Kenkyū-buntansha): 井本 博文 東北大学, 大学病院, 助教 (20754922) ; 内藤 剛 東北大学, 医学系研究科, 准教授 (50291258)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000); Fiscal Year 2018: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 代謝改善手術 / NASH / duodeno-jejunal baypass / bilio-pancreatic limb / Duodenal-jejunal bypass / Bilio-pancreatic limb / 肥満 / 糖尿病 / 胆汁酸 / 酸化ストレス

Outline of Final Research Achievements

After duodenal-jejunal bypass (DJB) is performed, remarkable effects of suppressing weight gain and improving diabetic control are observed. Although the effect is canceled by resection of the bilio-pancreatic limb (BPL). In other words, the existence of BPL is important for the effect of metabolic surgery. In this study, we examined the effects of surgery on diet-induced NASH model rats. In the DJB group, a histological improvement in NASH was observed, but the effect was canceled in the BPL resection group. Similar to the diabetic improvement effect, it was confirmed that DJB's NASH improvement effect was canceled by BPL resection.

Academic Significance and Societal Importance of the Research Achievements

肥満の増加と供にNASHは増加傾向であり、肝硬変や肝細胞癌の原因となり得る疾患である。NASHに対して減量以外の有効な治療法が無いが、近年、減量手術（代謝改善手術）によるNASHの改善が報告されており、手術が有効な治療法として注目されている。本研究は、NASHに対する代謝改善手術の理論的背景やバイパス長に一定の根拠を付すものである。また、今回得られた知見は、病因や改善機序の解明の一助となり、予防や創薬を含めた治療法の確立に貢献できるものと考える。

Research Products

• [Journal Article] Changes in Enterohepatic Circulation after Duodenal-Jejunal Bypass and Reabsorption of Bile Acids in the Bilio-Pancreatic Limb (2019)
  • Author(s): Ise Ichiro、Tanaka Naoki、Imoto Hirofumi、Maekawa Masamitsu、Kohyama Atsushi、Watanabe Kazuhiro、Motoi Fuyuhiko、Unno Michiaki、Naitoh Takeshi
  • Journal Title: Obesity Surgery Volume: e-pub Issue: 6 Pages: 1901-1910
  • DOI: 10.1007/s11695-019-03790-y
  • Peer Reviewed
• [Journal Article] 【肥満症例に対する腹腔鏡下手術】総論 肥満症例に対する腹腔鏡下手術のpros and cons(解説/特集) (2019)
  • Author(s): 内藤剛
  • Journal Title: 外科 Volume: 81 Pages: 207-210
• [Journal Article] 【NAFLDとNASHの現況と展望-国民病となったNAFLD/NASHの疾患概念の変遷と問題点】Key words 減量手術(bariatric surgery)とNASH改善効果(解説/特集) (2019)
  • Author(s): 内藤剛
  • Journal Title: カレントテラピー Volume: 37 Pages: 96-96
• [Journal Article] Increased Bile Acid Signals After Duodenal-Jejunal Bypass Improve Non-alcoholic Steatohepatitis (NASH) in a Rodent Model of Diet-Induced NASH. (2018)
  • Author(s): Tsuchiya T, Naitoh T, Nagao M, Tanaka N, Watanabe K, Imoto H, Miyachi T, Motoi F, Unno M.
  • Journal Title: Obes Surg. Volume: 28 Issue: 6 Pages: 1643-1652
  • DOI: 10.1007/s11695-017-3065-z
  • Peer Reviewed
• [Journal Article] Efficacy of Sleeve Gastrectomy with Duodenal-Jejunal Bypass for the Treatment of Obese Severe Diabetes Patients in Japan: a Retrospective Multicenter Study. (2018)
  • Author(s): Naitoh T, Kasama K, Seki Y, Ohta M, Oshiro T, Sasaki A, Miyazaki Y, Yamaguchi T, Hayashi H, Imoto H, Tanaka N, Unno M.
  • Journal Title: Obes Surg. Volume: 28 Issue: 2 Pages: 497-505
  • DOI: 10.1007/s11695-017-2874-4
  • Peer Reviewed / Open Access
• [Journal Article] 【肥満症 概念・診断・治療の現状と展望】 セミナー 肥満症に対処するための具体的知識 肥満外科治療に伴う減量・代謝改善のメカニズム (2018)
  • Author(s): 井本 博文, 内藤 剛
  • Journal Title: Medical Practice Volume: 35 Pages: 255-258
• [Journal Article] 減量手術・代謝改善手術 (2018)
  • Author(s): 田中直樹、井本博文、海野倫明、内藤剛
  • Journal Title: 消化器・肝臓内科 Volume: 3 Pages: 203-208
• [Presentation] 十二指腸空腸バイパス術後の胆膵路における胆汁酸吸収機序の解明 (2019)
  • Author(s): 上野 知尭, 田中 直樹, 井本 博文, 前川 正充, 市川 英孝, 小野 翼, 神山 篤史, 渡辺 和宏, 元井 冬彦, 海野 倫明, 内藤 剛
  • Organizer: 第40回日本肥満学会・第37回日本肥満症治療学会学術集会
• [Presentation] 消化管の情報発信-臓器間ネットワークと肥満- 胆汁酸の動態から見たMetabolic surgeryの作用機序 (2019)
  • Author(s): 田中 直樹, 井本 博文, 伊勢 一郎, 上野 知尭, 市川 英孝, 渡辺 和宏, 神山 篤史, 大沼 忍, 武者 宏昭, 元井 冬彦, 亀井 尚, 海野 倫明, 内藤 剛
  • Organizer: 第40回日本肥満学会・第37回日本肥満症治療学会学術集会
• [Presentation] 十二指腸空腸バイパス手術における胆膵路の長さの違いが代謝に及ぼす影響とその機序の検討 (2019)
  • Author(s): 伊勢 一郎, 田中 直樹, 井本 博文, 前川 正充, 神山 篤史, 渡辺 和宏, 元井 冬彦, 亀井 尚, 内藤 剛, 海野 倫明
  • Organizer: 第40回日本肥満学会・第37回日本肥満症治療学会学術集会
• [Presentation] Mechanism of Reabsorption of Bile Acids in Bilio-Pancreatic Limb after Duodenal-Jejunal Bypass (2019)
  • Author(s): Tomotaka Ueno, Naoki Tanaka, Hirofumi Imoto, Masamitsu Maekawa, Atsushi Kohyama, Kazuhiro Watanabe, Fuyuhiko Motoi, Takashi Kamei, Michiaki Unno, Takeshi Naitoh
  • Organizer: 24th World Congress of International Federation for the Surgery of Obesity & Metabolic disorders.
  • Int'l Joint Research
• [Presentation] 十二指腸空腸バイパス手術における胆膵路の長さの違いが代謝に及ぼす影響とその機序の検討 (2019)
  • Author(s): 伊勢 一郎, 田中 直樹, 井本 博文, 前川 正充, 神山 篤史, 渡辺 和宏, 元井 冬彦, 亀井 尚, 内藤 剛, 海野 倫明
  • Organizer: 第119回日本外科学会定期学術集会
• [Presentation] The changes of enterohepatic circulation after duodenal-jejunal bypass; reabsorption of bile acids in the bilio-pancreatic limb. (2019)
  • Author(s): Ise I, Imoto I, Tanaka N, Maekawa M, Ichikawa H, Ueno T, Kohyama A, Watanabe K, Motoi F, Kamei T, Unno M, Naitoh T
  • Organizer: International Federation of Surgery for Obesity, Asia Pacific Chapter 2019.
  • Int'l Joint Research
• [Presentation] 十二指腸空腸バイパス手術における胆膵路の長さの違いが代謝に及ぼす影響とその機序の検 (2018)
  • Author(s): 伊勢 一郎, 田中 直樹, 上野 知尭, 小野 智之, 井本 博文, 神山 篤史, 渡辺 和宏, 前川 正充, 亀井 尚, 内藤 剛, 海野 倫明
  • Organizer: 第36回 日本肥満症治療学会
• [Presentation] 肥満治療の最前線 新規薬剤開発から外科治療 日本における肥満と糖尿病の外科的治療の現状と将来展望(Forefront research into obesity management: from development of novel agents to surgical therapy Current status and future perspective of surgical treatment for obesity and diabetes in Japan) (2018)
  • Author(s): 内藤 剛, 井本 博文, 田中 直樹, 元井 冬彦, 亀井 尚, 海野 倫明
  • Organizer: 第61回 日本糖尿病学会
• [Presentation] Efficacy of sleeve gastrectomy with duodenal-jejunal bypass for the treatment of obese severe diabetes patients in Japan Speaker: Takeshi Naito (2018)
  • Author(s): Naitoh T, Tanaka N, Imoto H et al.
  • Organizer: Congress of the Asia Pacific Metabolic and Bariatric Surgery Society
  • Int'l Joint Research
• [Presentation] The need of laparoscopic sleeve bypass surgery -Mechanism and Effect- (2018)
  • Author(s): Naitoh T, Tanaka N, Imoto H et al.
  • Organizer: Congress of the Asia Pacific Metabolic and Bariatric Surgery Society
  • Int'l Joint Research
• [Presentation] Mechanism of the anti-diabetic effect of metabolic surgeries (2018)
  • Author(s): Naitoh T, Tanaka N, Imoto H et al.
  • Organizer: Congress of the Asia Pacific Metabolic and Bariatric Surgery Society
  • Int'l Joint Research
• [Presentation] Preoperative intensive weight loss program by multidisciplinary team approach for super obese patients scheduled for bariatric surgery (2018)
  • Author(s): Tanaka N, Naitoh T, Imoto H et al.
  • Organizer: Congress of the Asia Pacific Metabolic and Bariatric Surgery Society
  • Int'l Joint Research
• [Presentation] Outcomes of bariatric surgery for Japanese morbid obese patients (2018)
  • Author(s): Imoto H, Tanaka N, Naitoh T, et al.
  • Organizer: Congress of the Asia Pacific Metabolic and Bariatric Surgery Society
  • Int'l Joint Research
• [Presentation] Duodenal-jejunal bypass improves non-alcoholic steatohepatitis in rats (2018)
  • Author(s): Tsuchiya T, Naitoh T, Tanaka N, Imoto H et al.
  • Organizer: Congress of the Asia Pacific Metabolic and Bariatric Surgery Society
• [Presentation] The effect of the biliopancreatic limb on energy expenditure after duodenal-jejunal bypass in diet induced obesity rats (2018)
  • Author(s): Kono E, T, Naitoh T, Tanaka N, Imoto H et al.
  • Organizer: Congress of the Asia Pacific Metabolic and Bariatric Surgery Society
• [Presentation] The function of the biliopancreatic limb after duodenal-jejunal bypass in type2 diabetes rat model (2018)
  • Author(s): Ise I, T, Naitoh T, Tanaka N, Imoto H et al.
  • Organizer: Congress of the Asia Pacific Metabolic and Bariatric Surgery Society
• [Presentation] The effect of the biliopancreatic limb on energy expenditure after duodenal-jejunal bypass in diet induced obesity rats. (2017)
  • Author(s): E. Kono, N.tanaka, H. Imoto, T. Naitoh
  • Organizer: 22nd world congress, international federation for the surgery of obesity and metabolic disorders
  • Int'l Joint Research
• [Presentation] Impact of sleeve gastrectomy with duodenal-jejunal bypass for the treatment of T2DM with low mABCD score patients in japan. (2017)
  • Author(s): H. Imoto, N.tanaka, T. Naitoh
  • Organizer: 22nd world congress, international federation for the surgery of obesity and metabolic disorders
  • Int'l Joint Research
• [Presentation] 十二指腸空腸バイパス術後のエネルギー代謝におけるbiliopancreatic limbの役割 (2017)
  • Author(s): 河野 えみ子, 長尾 宗紀, 上野 知尭, 伊勢 一郎, 土屋 堯裕, 井本 博文, 田中 直樹, 武者 宏昭, 内藤 剛, 海野 倫明
  • Organizer: 第３5回 日本肥満症治療学会学術集会
• [Presentation] 十二指腸空腸バイパスにおけるbiliopancreatic limbがエネルギー代謝に及ぼす影響の検討 (2017)
  • Author(s): 河野 えみ子, 長尾 宗紀, 土屋 尭裕, 井本 博文, 渡辺 和宏, 田中 直樹, 大沼 忍, 大塚 英郎, 水間 正道, 坂田 直昭, 中川 圭, 林 洋毅, 森川 孝則, 武者 宏昭, 元井 冬彦, 内藤 剛, 海野 倫明
  • Organizer: 第117回 日本外科学会定期学術集会