Elucidation of the mechanism of onset of steatohepatitis and prevention of pathogenesis with the food ingredients by targeting Nrf2

• Project/Area Number: 23580188
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Food science
• Research Institution: Kinki University
• Principal Investigator: TANAKA Yuji 近畿大学, 医学部附属病院, 講師 (00465650)
• Co-Investigator(Kenkyū-buntansha): KAMISAKO Toshinori 近畿大学, 医学部附属病院, 教授 (20233934)
• Research Collaborator: OGAWA Hiroshi 帝塚山学院大学, 人間科学部, 教授 (00133546)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2013: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2012: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: Nrf2 / 酸化ストレス / 脂肪肝炎 / 食品機能 / 非アルコール性脂肪肝炎 / 鉄過剰蓄積

Research Abstract

Oxidative stress has been implicated in the transition from simple hepatic steatosis to nonalcoholic steatohepatitis (NASH). The Nuclear factor E2-related factor 2 (Nrf2) transcription factor serves as a cellular sensor for oxidative and electrophilic stress. Nrf2 deletion dysregulates hepatic mRNA expression of lipid and iron metabolism related genes and tends to increase hepatic triglycerides and iron, suggesting that Nrf2 may play a role in the pathogenesis of NASH. Wasabi derivative 6-methylsulfinylhexyl isothiocyanate, a potent Nrf2 activator, prevented the fatty liver produced by a high-fat diet in mice. These data indicated that Nrf2 could prevent the onset and progression of steatohepatitis.

Research Products

• [Journal Article] Dysregulated expression of fatty acid oxidation enzymes and iron-regulatory genes in livers of Nrf2-null mice (2012)
  • Author(s): Tanaka Y, Ikeda T, Yamamoto K, Ogawa H, Kamisako T.
  • Journal Title: Journal of Gastroenterology and Hepatology Volume: 27 Issue: 11 Pages: 1711-1717
  • DOI: 10.1111/j.1440-1746.2012.07180.x
  • Peer Reviewed
• [Presentation] ワサビ由来6-メチルスルフィニルヘキシルイソチオシアネートはマウスの高脂肪食誘発性脂肪肝をNrf2依存性に改善する (2014)
  • Author(s): 田中裕滋、池田高紀、山本和夫、小川博、上硲俊法
  • Organizer: 第50回日本肝臓学会総会
  • Place of Presentation: 東京
• [Presentation] Wasabi derivative 6-methylsulfinylhexyl isothiocyanate, a potent Nrf2 activator, prevents the fatty liver produced by a high-fat diet but does not attenuate hepatic iron overload in mice (2013)
  • Author(s): Yuji Tanaka
  • Organizer: 64th Annual Meeting of the American Association for the Study of Liver Diseases
  • Place of Presentation: Walter E. Washington Convention Center (アメリカワシントンDC)
  • Year and Date: 2013-11-02
• [Presentation] Wasabi derivative 6-methylsulfinylhexyl isothiocyanate, a potent Nrf2 activator, prevents the fatty liver produced by a high-fat diet but did not attenuate hepatic iron overload in mice (2013)
  • Author(s): Yuji Tanaka, Toshinori Kamisako
  • Organizer: 64th Annual Meeting of the American Association for the Study of Liver Diseases
  • Place of Presentation: Washington, D.C., USA