Molecular mechanism and biomarkers for non-alcoholic steatohepatitis

• Project/Area Number: 25461369
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Kobe Gakuin University
• Principal Investigator: Kume Noriaki 神戸学院大学, 薬学部, 教授 (20252455)
• Co-Investigator(Kenkyū-buntansha): HIRAOKA Yoshinori 神戸学院大学, 薬学部, 助教 (60397552)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); 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: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 脂肪肝 / 炎症 / 線維化 / 肝炎

Outline of Final Research Achievements

As a mouse model for non-alcoholic steatohepatitis (NASH),　a cholie-deficient amin acid-defined high fat diet (CDAHFD) model has been developed. In this study, we explored the effects of CDAHFD on serum lipid profiles, as well as body weight. We have revealed that CDAHFD diet signidicaly reduced serum total cholesterol (TCho) and triglyceride (TG) levels, as well as body weight. Furthermore, reductions in serum TCho and TG, as well as body weight, showed significant inverse correlation with elevations in markers for NASH, such as hapatic triglyceride contents, hepatic TNF-alpha mRNA expression, and serum alanine aminotransferese (ALT) levels. Thus, this CDAHFD model in mice appears to have inconsistent points with NASH in humans. More suitable mouse models for human NASH shoud be developed in the future.

Research Products

• [Journal Article] Plasma soluble lectin-like oxidized low-density lipoprotein receptor-1 as a novel prognostic biomarker in patients with ST-segment elevation acute myocardial infarction. (2015)
  • Author(s): Higuma T, Abe N, Tateyama S, Endo T, Shibutani S, Yokoyama H, Harada K, Yamada M, Tomita H, Hanada H, Osanai T, Kume N, Okumura K
  • Journal Title: Cieculation Journal Volume: in press
  • NAID: 130004927094
  • Peer Reviewed / Open Access
• [Journal Article] Serum lipid goal attainment in chronic kidney disease (CKD) under the Japan Atherosclerosis Society 2012 guideline: a single center study (2015)
  • Author(s): Shimizu R, Torii H, Yasuda D, Hiraoka Y, Kitada N, Hashida T, Yoshimoto A, Kita T, Kume N
  • Journal Title: Journal of Atherosclerosis and Thrombosis Volume: in press
  • Peer Reviewed / Open Access
• [Journal Article] MicroRNA-33b knock-in mice for an intron of sterol regulatory element-binding factor 1 (Srebf1) exhibit reduced HDL-C in vivo. (2014)
  • Author(s): Horie T, Nishino T, Baba O, Kuwabara Y, Nakao T, Nishiga M, Usami S, Izuhara M, Nakazeki F, Ide Y, Koyama S, Sowa N, Yahagi N, Shimano H, Nakamura T, Hasegawa K, Kume N, Yokode M, Kita T, Kimura T, Ono K.
  • Journal Title: Scientific Reports Volume: 4 Issue: 1 Pages: 5312-5312
  • DOI: 10.1038/srep05312
  • Peer Reviewed / Open Access
• [Journal Article] MicroRNA-33 regulates sterol regulatory element-binding protein 1 expression in mice. (2013)
  • Author(s): Horie T, Nishino T, Baba O, Kuwabara Y, Nakao T, Nishiga M, Usami S, Izuhara M, Sowa N, Yahagi N, Shimano H, Matsumura S, Inoue K, Marusawa H, Nakamura T, Hasegawa K, Kume N, Yokode M, Kita T, Kimura T, Ono K
  • Journal Title: Nat Commun. Volume: 4:2883 Issue: 1 Pages: 2883-2883
  • DOI: 10.1038/ncomms3883
  • NAID: 120005349007
  • Peer Reviewed / Open Access
• [Journal Article] Soluble lectin-like oxidized LDL receptor-1 (sLOX-1) as a valuable diagnostic marker for rupture of thin-cap fibroatheroma: verification by optical coherence tomography (2013)
  • Author(s): Kobayashi N, Takano M, Hata N, Kume N, Yamamoto M, Yokoyama S, Shinada T, Tomita K, Shirakabe A, Otsuka T, Seino Y, Mizuno K:
  • Journal Title: International Journal of Cardiology Volume: 168 Pages: 3217-3223
  • Peer Reviewed