Regulation of metabolism and inflammation through hepatic vagus nerve system in steatohepatitis

• Project/Area Number: 15K15495
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Kyoto University
• Principal Investigator: Taura Kojiro 京都大学, 医学研究科, 講師 (80378629)
• Co-Investigator(Kenkyū-buntansha): 上本 伸二 京都大学, 医学研究科, 教授 (40252449) ; 波多野 悦朗 京都大学, 医学研究科, 客員研究員 (80359801)
• Research Collaborator: NISHIO Takahiro 京都大学, 大学院医学研究科, 大学院生 ; Yamamoto Gen 京都大学, 大学院医学研究科, 大学院生 ; TANABE Kazutaka 京都大学, 大学院医学研究科, 大学院生 ; OKUDA Yukihiro 京都大学, 大学院医学研究科, 大学院生 ; IKENO Yoshinobu 京都大学, 大学院医学研究科, 大学院生
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: NASH / 迷走神経 / クッパー細胞 / ニコチン性アセチルコリン受容体α7

Outline of Final Research Achievements

Nonalcoholic steatohepatitis (NASH) is a chronic liver disease characterized by steatosis with progressive inflammation. Kupffer cells, which are liver-resident macrophages, play a central role in promoting hepatic inflammation by innate immune responses in NASH. The efferent vagus nerve signaling is known to have an anti-inflammatory effect on immune cells via the α7 nicotinic acetylcholine receptor (α7nAChR) pathway. This study demonstrated that the hepatic vagus nerve plays a key role in regulating the inflammatory response in Kupffer cells via the α7nAChR pathway and eventually contributed to the suppression of NASH progression, by using mouse experimental model of NASH.

Research Products

• [Journal Article] Chronological Profiling of Plasma Native Peptides after Hepatectomy in Pigs: Toward the Discovery of Human Biomarkers for Liver Regeneration. (2017)
  • Author(s): Iguchi K, Hatano E, Nirasawa T, Iwasaki N, Sato M, Yamamoto G, Yamanaka K, Okamoto T, Kasai Y, Nakamura N, Fuji H, Sakai T, Kakuda N, Seo S, Taura K, Tashiro K, Uemoto S, Ikegawa M.
  • Journal Title: PLoS One. Volume: 12 Issue: 1 Pages: e0167647-e0167647
  • DOI: 10.1371/journal.pone.0167647
  • NAID: 120005980866
  • Peer Reviewed / Open Access
• [Journal Article] Hepatic vagus nerve regulates Kupffer cell activation via α7 nicotinic acetylcholine receptor in nonalcoholic steatohepatitis. (2017)
  • Author(s): Nishio T, Taura K, Iwaisako K, Koyama Y, Tanabe K, Yamamoto G, Okuda Y, Ikeno Y, Yoshino K, Kasai Y, Okuno M, Seo S, Sakurai T, Asagiri M, Hatano E, Uemoto S
  • Journal Title: Journal of Gastroenterology Volume: 印刷中 Issue: 8 Pages: 965-976
  • DOI: 10.1007/s00535-016-1304-z
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Phase I clinical trial of olprinone in liver surgery. (2016)
  • Author(s): Fuji H, Hatano E, Iguchi K, Yamanaka K, Yoh T, Ikeno Y, Seo S, Taura K, Yasuchika K, Tanaka S, Ishii H, Kobayashi M, Ueno K, Uemoto S.
  • Journal Title: Surg Today. Volume: Epub ahead of print Issue: 8 Pages: 918-927
  • DOI: 10.1007/s00595-016-1461-y
  • Peer Reviewed
• [Journal Article] Living donor liver transplantation with a left trisegmental graft from a donor with anomalous branching of the portal vein. (2016)
  • Author(s): Taura K, Kaido T, Anazawa T, Yagi S, Okajima H, Uemoto S.
  • Journal Title: Liver Transpl. Volume: Epub ahead of print Issue: 6 Pages: 853-856
  • DOI: 10.1002/lt.24687
  • Peer Reviewed
• [Journal Article] Usefulness of Mac-2 Binding Protein Glycosylation Isomer for Prediction of Posthepatectomy Liver Failure in Patients With Hepatocellular Carcinoma. (2016)
  • Author(s): Okuda Y, Taura K, Yoshino K, Ikeno Y, Nishio T, Yamamoto G, Tanabe K, Koyama Y, Hatano E, Tanaka S, Uemoto S.
  • Journal Title: Ann Surg. Volume: Epub ahead of print
  • Peer Reviewed
• [Journal Article] Impact of the preoperative quantity and quality of skeletal muscle on outcomes after resection of extrahepatic biliary malignancies. (2016)
  • Author(s): Okumura S, Kaido T, Hamaguchi Y, Fujimoto Y, Kobayashi A, Iida T, Yagi S, Taura K, Hatano E, Uemoto S.
  • Journal Title: Surgery Volume: 159 Issue: 3 Pages: 821-833
  • DOI: 10.1016/j.surg.2015.08.047
  • Peer Reviewed / Open Access
• [Journal Article] Prediction of posthepatectomy liver failure based on liver stiffness measurement in patients with hepatocellular carcinoma. (2016)
  • Author(s): Nishio T, Taura K, Koyama Y, Tanabe K, Yamamoto G, Okuda Y, Ikeno Y, Seo S, Yasuchika K, Hatano E, Okajima H, Kaido T, Tanaka S, Uemoto S.
  • Journal Title: Surgery Volume: 159 Issue: 2 Pages: 399-408
  • DOI: 10.1016/j.surg.2015.06.024
  • Peer Reviewed
• [Journal Article] Controversies over the Epithelial-to-Mesenchymal Transition in Liver Fibrosis. (2016)
  • Author(s): Taura K, Iwaisako K, Hatano E, Uemoto S.
  • Journal Title: J Clin Med. Volume: 5 Issue: 1 Pages: 1-11
  • DOI: 10.3390/jcm5010009
  • NAID: 120005825917
  • Peer Reviewed / Open Access
• [Journal Article] Migration of splenic lymphocytes promotes liver fibrosis through modification of T helper cytokine balance in mice (2015)
  • Author(s): Tanabe K, Taura K, Koyama Y, Yamamoto G, Nishio T, Okuda Y, Nakamura K, Toriguchi K, Takemoto K, Yamanaka K, Iwaisako K, Seo S, Asagiri M, Hatano E, Uemoto S.
  • Journal Title: Journal of Gastroenterology Volume: in press Issue: 10 Pages: 1054-1068
  • DOI: 10.1007/s00535-015-1054-3
  • Peer Reviewed
• [Journal Article] Usefulness of operative planning based on 3-dimensional CT cholangiography for biliary malignancies. (2015)
  • Author(s): Okuda Y, Taura K, Seo S, Yasuchika K, Nitta T, Ogawa K, Hatano E, Uemoto S.
  • Journal Title: Surgery Volume: 158 Issue: 5 Pages: 1261-1271
  • DOI: 10.1016/j.surg.2015.04.021
  • NAID: 120005689198
  • Peer Reviewed
• [Presentation] 肝・胆道癌手術や生体肝移植ドナー手術プラニングにおける""all-in-one"" 3Dイメージの有用性 (2016)
  • Author(s): 田浦 康二朗 奥田 雄紀浩 瀬尾 智 安近 健太郎 岡島 英明 海道 利実 波多野 悦朗 上本 伸二
  • Organizer: 日本消化器外科学会総会
  • Place of Presentation: 徳島
  • Year and Date: 2016-07-14
• [Presentation] 非侵襲的肝線維化指標に基づく肝切除適応アルゴリズム作成へ向けて (2016)
  • Author(s): 田浦康二朗、西尾太宏、奥田雄紀浩、田邉和孝、山本玄、池野嘉信、吉野健二、瀬尾智、安近健太郎、岡島英明、海道利実、波多野悦朗、上本伸二
  • Organizer: 日本肝癌研究会
  • Place of Presentation: 東京
  • Year and Date: 2016-07-01
• [Presentation] Evaluation of liver functional reserve based on noninvasive assessment of liver fibrosis (2016)
  • Author(s): Taura Kojiro, Nishio Takahiro, Okuda Yukihiro, Tanabe Kazutaka, Yamamoto Gen, Ikeno Yoshinobu, Yoshino Kenji, Seo Satoru, Yasuchika Kentaro, Okajima Hideaki, Kaido Toshimi, Hatano Etsuro, Uemoto Shinji
  • Organizer: 日本肝胆膵外科学会・学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2016-06-02
• [Presentation] 肝細胞癌切除前肝予備能評価としてのAcoustic Radiation Force Impulse (ARFI)による肝硬度測定の有用性の検討 (2016)
  • Author(s): 田浦康二朗、波多野悦朗、上本伸二
  • Organizer: 日本肝臓学会総会
  • Place of Presentation: 幕張
  • Year and Date: 2016-05-19
• [Presentation] 肝門部領域癌手術プラニングにおける”all-in-one” 3Dイメージの有用性 (2016)
  • Author(s): 田浦康二朗、奥田雄紀浩、上本伸二
  • Organizer: 日本外科学会定期学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2016-04-14
• [Presentation] Prediction of posthepatectomy liver failure based on preoperative liver fibrosis assessment: comparison of Wisteria floribunda agglutinin-positive Mac-2 binding protein and liver stiffness measurement (2015)
  • Author(s): Takahiro Nishio, Kojiro Taura, Kazutaka Tanabe, Gen Yamamoto, Yukihiro Okuda, Yoshinobu Ikeno, Satoru Seo, Kentaro Yasuchika, Etsuro Hatano, Hideaki Okajima, Toshimi Kaido, Shinji Uemoto
  • Organizer: Annual meeting of the American Association for the Study of Liver Disease
  • Place of Presentation: San Francisco
  • Year and Date: 2015-11-13
• [Presentation] Preoperative assessment of liver fibrosis and posthepatectomy liver failure by acoustic radiation force impulse (ARFI) in hepatocellular carcinoma patients (2015)
  • Author(s): Kojiro Taura, Takahiro Nishio, Yukinori Koyama, Kazutaka Tanabe, Gen Yamamoto, Yukihiro Okuda, Yoshinobu Ikeno, Kenji Yoshino, Etsuro Hatano, Hideaki Okajima, Toshimi Kaido, Shinji Uemoto
  • Organizer: 日本消化器関連学会週間
  • Place of Presentation: 東京
  • Year and Date: 2015-10-08
• [Presentation] 肝臓迷走神経遮断は代謝調節および免疫応答制御の異常を介して非アルコール性脂肪性肝炎(NASH)を悪化させる (2015)
  • Author(s): 西尾 太宏 田浦 康二朗 田邉 和孝 山本 玄 奥田 雄紀浩 祝迫 惠子 波多野 悦朗 上本 伸二
  • Organizer: 日本外科学会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-04-16