Involvement of stress and sympathetic nervous system on the progression in NASH

• Project/Area Number: 25461014
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Aichi Medical University
• Principal Investigator: Nakade Yukiomi 愛知医科大学, 医学部, 准教授 (70431400)
• Co-Investigator(Kenkyū-buntansha): Ito Kiyoaki 愛知医科大学, 肝胆膵内科, 教授 (50551420)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: ストレス / 交感神経系 / ＮＡＳＨ / ＮＡＦＬＤ / 脂肪性肝炎 / 脂肪肝 / ＣＰＴ１ / NASH / 交感神経 / 肥満 / 糖尿病 / 高脂肪食 / CRF / 非アルコール性脂肪性肝炎 / ノルアドレナリン / フェニレフリン / イソプロテレノル / ＣＲＦ

Outline of Final Research Achievements

To investigate the effect of sympathetic nervous system which is activated by stress on NASH, alpha-adrenergic　receptor　agonist,　phenylephrine　and beta-adrenergic　receptor　agonist,　isoproterenol were administered to mice concurrent with high fat diet feeding. Four weeks after the commencement of feeding, hepatic histological findings were evaluated. While hepatic steatosis was not changed by phenylephrine, isoproterenol augmented hepatic steatosis. Microarray and Real time PCR showed that hepatic CPT1 mRNA level, which is related to beta-oxidation in mitocondria tended to be decreased in isoproterenol-treated mice. These indicates that beta-adrenergic agonist stimulates hepatic steatosis through the suppression of beta-oxidation in NASH.

Research Products

• [Journal Article] Glucagon-like peptide-1 analogue prevents nonalcoholic steatohepatitis in non-obese mice. (2016)
  • Author(s): Yamamoto T, Nakade Y, Yamauchi T, Kobayashi Y, Ishii N, Ohashi T, Ito K, Sato K, Fukuzawa Y, Yoneda M.
  • Journal Title: World J Gastroenterol Volume: 22 Issue: 8 Pages: 2512-2523
  • DOI: 10.3748/wjg.v22.i8.2512
  • Peer Reviewed / Open Access
• [Journal Article] Case of cholangiocellular carcinoma in a patient with glycogen storage disease type Ia. (2015)
  • Author(s): Kanamori H1, Nakade Y, Yamamoto T, Kobayashi Y, Sato K, Ito K, Ohashi T, Nakao N, Ishii N, Takahashi E, Yokoi T, Nakao H, Kurokawa T, Yamaguchi C, Yoneda M.
  • Journal Title: Hepatol. Res. Volume: 45 Issue: 4 Pages: 494-499
  • DOI: 10.1111/hepr.12366
  • Peer Reviewed
• [Journal Article] Diagnostic accuracy of real-time tissue elastography for the staging of liver fibrosis: a meta-analysis. (2015)
  • Author(s): Kobayashi K, Nakao H, Nishiyama T, Lin Y, Kikuchi S, Kobayashi Y, Yamamoto T, Ishii N, Ohashi T, Satoh K, Nakade Y, Ito K, Yoneda M.
  • Journal Title: European Radiology Volume: 25 Issue: 1 Pages: 230-238
  • DOI: 10.1007/s00330-014-3364-x
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] What are the important lifestyle interventions for preventing the progression of impaired glucose tolerance (IGT) and type 2 diabetes in non-alcoholic fatty liver disease (NAFLD) patients? (2014)
  • Author(s): Nakade Y, Yoneda M
  • Journal Title: Internal Medicine Volume: 53 Pages: 1399-1400
  • Peer Reviewed
• [Journal Article] Pretreatment prediction of the outcome of response-guided peginterferon-α and ribavirin therapy for chronic hepatitis C (2014)
  • Author(s): Masaki N, Sugiyama M, Shimada N, Tanaka Y, Nakamuta M, Izumi N, Watanabe S, Tsubota A, Komatsu M, Masaki T, Enomoto N, Yoneda M, Murata K, Ito K, Koike K, Mizokami M.
  • Journal Title: J Gastroenterol Hepatol Volume: 29 Issue: 12 Pages: 1996-2005
  • DOI: 10.1111/jgh.12646
  • Peer Reviewed
• [Journal Article] Ex vivo induction of IFN-λ3 by a TLR7 agonist determines response to Peg-IFN/ribavirin therapy in chronic hepatitis C patients. (2014)
  • Author(s): Murata K, Sugiyama M, Kimura T, Yoshio S, Kanto T, Kirikae I, Saito H, Aoki Y, Hiramine S, Matsui T, Ito K, Korenaga M, Imamura M, Masaki N, Mizokami M.
  • Journal Title: J Gastroenterology Volume: 49 Pages: 126-137
  • Peer Reviewed
• [Journal Article] Angiotensin II type 1 receptor antagonist prevents hepatic carcinoma in rats with nonalcoholic steatohepatitis. (2013)
  • Author(s): Tamaki, Y., Y. Nakade, T. Yamauchi, Y. Makino, S. Yokohama, M. Okada, K. Aso, H. Kanamori, T. Ohashi, K. Sato, H. Nakao, M. Haneda and M. Yoneda
  • Journal Title: J Gastroenterology Volume: 48 Pages: 491-503
  • Peer Reviewed
• [Journal Article] High levels of hepatitis B virus after the onset of disease lead to chronic infection in patients with acute hepatitis B. (2013)
  • Author(s): Yotsuyanagi H, Ito K, Yamada N, Takahashi H, Okuse C, Yasuda K, Suzuki M, Moriya K, Mizokami M, Miyakawa Y, Koike K.
  • Journal Title: Clin Infect Dis. Volume: 57 Pages: 935-942
  • Peer Reviewed
• [Presentation] NAFLDにおける交感神経β受容体の関与 (2016)
  • Author(s): 中出幸臣 井上匡央 山本高也 小林佑次 石井紀光 大橋知彦 佐藤顕 伊藤清顕 福沢嘉孝 米田政志
  • Organizer: 第102回日本消化器病学会総会
  • Place of Presentation: 東京
  • Year and Date: 2016-04-22
• [Presentation] The relationship among fatty liver, endogenous Glucagon like peptide-1 (GLP-1) and bile acid in spontaneously diabetic torii fatty (SDTF) rat (2015)
  • Author(s): Tomohiko Ohashi, Yukiomi Nakade and Masashi Yoneda
  • Organizer: 第19回日本肝臓学会大会
  • Place of Presentation: 東京
  • Year and Date: 2015-10-09