Analysis of dysregulated lipid and iron metabolisms in patients with nonalcoholic fatty liver disease

• Project/Area Number: 24590990
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: MITSUYOSHI Hironori 京都府立医科大学, 医学(系)研究科(研究院), 講師 (30363972)
• Co-Investigator(Kenkyū-buntansha): YASUI Kohichiroh 京都府立医科大学, 医学研究科, 准教授 (30323695)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2014: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: 非アルコール性脂肪性肝疾患 / inflammasome / NLRP3 / NASH

Outline of Final Research Achievements

Relationships between single nucleotide polymorphisms (SNPs) of GP120 or ferroportin and NAFLD development were examined. However, no significant relationship was identified. Now, prospective studies on SNP of adiponutrin in NAFLD patients are ongoing. Subsequently, the role of inflammasomes for the pathogenesis of NAFLD was examined. The expression of NLRP3 infalmassome-related molecules was increased in the liver of NAFLD. IL-1β and IL-18 produced by NLRP3 activation in hepatic macrophages and Kupffer cells were associated with histological inflammation or serum transaminases.

Research Products

• [Journal Article] Blockade of interleukin 6 signalling ameliorates systemic insulin resistance through upregulation of glucose uptake in skeletal muscle and improves hepatic steatosis in high-fat diet fed mice (2015)
  • Author(s): Yamaguchi K, Nishimura T, Ishiba H, Seko Y, Okajima A, Fujii H, Tochiki N, Umemura A, Moriguchi M, Sumida Y, Mitsuyoshi H, Yasui K, Minami M, Okanoue T, Itoh Y
  • Journal Title: Liver Int Volume: 35 Issue: 2 Pages: 550-61
  • DOI: 10.1111/liv.12645
  • Peer Reviewed
• [Journal Article] Serum alanine aminotransferase predicts the histological course of non-alcoholic steatohepatitis in Japanese patients (2014)
  • Author(s): Seko Y, Sumida Y, Tanaka S, Mori K, Taketani H, Ishiba H, Hara T, Okajima A, Yamaguchi K, Moriguchi M, Mitsuyoshi H, Kanemsa K, Yasui K, Minami M, Imai S, Itoh Y
  • Journal Title: Hepatol Res Volume: - Issue: 10
  • DOI: 10.1111/hepr.12456
  • Peer Reviewed
• [Journal Article] Predictors of malignancies and overall mortality in Japanese patients with biopsy-proven non-alcoholic fatty liver disease (2014)
  • Author(s): Seko Y, Sumida Y, Tanaka S, Taketani H, Kanemasa K, Ishiba H, Okajima A, Nishimura T, Yamaguchi K, Moriguchi M, Mitsuyoshi H, Yasui K, Minami M, Itoh Y
  • Journal Title: Hepatol Res Volume: - Issue: 7 Pages: 728-738
  • DOI: 10.1111/hepr.12407
  • Peer Reviewed / Open Access
• [Journal Article] Lower levels of insulin-like growth factor-1 standard deviation score are associated with histological severity of non-alcoholic fatty liver disease (2014)
  • Author(s): Sumida Y, Yonei Y, Tanaka S, Mori K, Kanemasa K, Imai S, Taketani H, Hara T, Seko Y, Ishiba H, Okajima A, Yamaguchi K, Moriguchi M, Mitsuyoshi H, Yasui K, Minami M, Itoh
  • Journal Title: Hepatol Res Volume: - Issue: 7 Pages: 1-11
  • DOI: 10.1111/hepr.12408
  • Peer Reviewed / Open Access
• [Journal Article] Effect of PNPLA3 rs738409 variant (I148M) on hepatic steatosis, necroinflammation, and fibrosis in Japanese patients with chronic hepatitis C (2014)
  • Author(s): Yasui K, Kawaguchi T, Shima T, Mitsuyoshi H, Seki K, Sendo R, Mizuno M, Itoh Y, Matsuda F, Okanoue T
  • Journal Title: J Gastroenterol Volume: -
  • Peer Reviewed
• [Journal Article] The 'donations for decreased ALT (D4D)' prosocial behavior incentive scheme for NAFLD patients (2014)
  • Author(s): Sumida Y, Yoshikawa T, Tanaka S, Taketani H, Kanemasa K, Nishimura T, Yamaguchi K, Mitsuyoshi H, Yasui K, Minami M, Naito Y, Itoh Y
  • Journal Title: Public Health Volume: 36 Issue: 4 Pages: 629-34
  • DOI: 10.1093/pubmed/fdt098
  • Peer Reviewed
• [Journal Article] The 'donations fordecreased ALT (D4D)' prosocial behavior incentive scheme for NAFLD patients. (2014)
  • Author(s): Sumida Y, Yoshikawa T, Tanaka S, Taketani H, Kanemasa K, Nishimura T, Yamaguchi K, Mitsuyoshi H, Yasui K, Minami M, Naito Y, Itoh Y.
  • Journal Title: J Public Health Volume: in press
  • Peer Reviewed
• [Journal Article] Epigenetic silencing of miR-335 and its host gene MEST in hepatocellular carcinoma. (2014)
  • Author(s): Dohi O, Yasui K, Gen Y, Takada H, Endo M, Tsuji K, Konishi C, Yamada N, Mitsuyoshi H, Naito Y, Tanaka S, Arii S, Yoshikawa T.
  • Journal Title: Int J Oncol, Volume: 42(2) Issue: 2 Pages: 411-418
  • DOI: 10.3892/ijo.2012.1724
  • Peer Reviewed
• [Journal Article] Aberrant expression of the PHF14 gene in biliary tract cancer cells. (2013)
  • Author(s): Akazawa T, Yasui K, Gen Y, Yamada N, Tomie A, Dohi O, Mitsuyoshi H, Yagi N, Itoh Y, Naito Y, Yoshikawa T.
  • Journal Title: Oncol Lett Volume: 5 Pages: 1849-1853
  • Peer Reviewed
• [Journal Article] Pathogenic Role of Iron Deposition in Reticuloendothelial Cells during the Development of Chronic Hepatitis C. (2013)
  • Author(s): Mitsuyoshi H, Yasui K, Yamaguchi K, Minami M, Okanoue T, Itoh Y.
  • Journal Title: Int J Hepatol Volume: Epub ahead of print Pages: 1-8
  • DOI: 10.1155/2013/686420
  • Peer Reviewed
• [Journal Article] Rosuvastatin ameliorates high-fat and high-cholesterol diet-induced nonalcoholic steatohepatitis in rats (2013)
  • Author(s): Okada Y, Yamaguchi K, Nakajima T, Nishikawa T, Jo M, Mitsumoto Y, Kimura H, Nishimura T, Tochiki N, Yasui K, Mitsuyoshi H, Minami M, Kagawa K, Okanoue T, Itoh Y
  • Journal Title: Liver Int Volume: 33 Issue: 2 Pages: 301-311
  • DOI: 10.1111/liv.12033
  • Peer Reviewed
• [Journal Article] Prediction of a favorable clinical course in hepatitis C virus carriers with persistently normal serum alanine aminotransferase levels: A long-term follow-up study (2013)
  • Author(s): Nishimura T, Yamaguchi K, Fujii H, Okada Y, Yokomizo C, Niimi T, Sumida Y, Yasui K, Mitsuyoshi H, Minami M, Umemura A, Shima T, Okanoue T, Itoh Y.
  • Journal Title: Hepatol Res Volume: 43 Issue: 5 Pages: 557-562
  • DOI: 10.1111/j.1872-034x.2012.01091.x
  • Peer Reviewed
• [Presentation] 非アルコール性脂肪性肝疾患（NAFLD）におけるInflammasomeの検討 (2015)
  • Author(s): 光吉博則、安居幸一郎、原 祐、石破 博、岡嶋 亮、瀬古裕也、山口寛二、森口理久、角田圭雄、南 祐仁、伊藤義人
  • Organizer: 第50回日本肝臓学会総会
  • Place of Presentation: 熊本
  • Year and Date: 2015-05-21
• [Presentation] C型肝炎におけるinflammasome活性化の検討 (2014)
  • Author(s): 光吉博則 安居幸一郎 西村健 山口寛二 森口理久 角田圭雄 南祐仁 伊藤義人
  • Organizer: 第50回日本肝臓学会総会
  • Place of Presentation: 東京
  • Year and Date: 2014-05-30
• [Presentation] Activation of the inflammasome is involved in the pathogenesis of chronic hepatitis C (2013)
  • Author(s): Hironori Mitsuyoshi, Kohichiroh Yasui, Takeshi Nishimura, Kanji Yamaguchi, Yoshio Sumida, Masahito Minami, Yoshito Itoh
  • Organizer: American Association for the Study of Liver Diseases
  • Place of Presentation: Washinton
• [Presentation] Distinctive pathogenic roles of iron deposition in hepatocytes and reticuloendothelial cells (2012)
  • Author(s): Hironori Mitsuyoshi Kouichirou Yasui Kanji Yamaguchi et al.
  • Organizer: American Association for the Study of Liver diseases
  • Place of Presentation: Boston
• [Presentation] C型慢性肝炎における 鉄蓄積パターンの解析 (2012)
  • Author(s): 光吉博則 安居幸一郎 山口寛二 ほか
  • Organizer: 第48回日本肝臓学会総会
  • Place of Presentation: 金沢