amino acids metabolism and immune abnormality in non alcoholic steatohepatitis

• Project/Area Number: 25460972
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Tohoku University
• Principal Investigator: KAKAZU Eiji 東北大学, 高度教養教育・学生支援機構, 助教 (20509377)
• Co-Investigator(Kenkyū-buntansha): KOGURE Takayuki 東北大学, 病院, 助教 (70400330) ; KONDO Yasuteru 東北大学, 医学系研究科, 非常勤講師 (70455822)
• 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: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 非アルコール性脂肪性肝炎 / メタボローム解析 / 門脈血

Outline of Final Research Achievements

We elucidated the differences of metabolite profiles in portal blood between normal mice and fatty liver genetic model mice (ob/ob and kk-Ay) by CE-TOFMS. The top 5% metabolites of portal blood that were higher in ob/ob compared to wild-type were Trimethylamine N-oxide (TMAO), phenaceturic acid, isethionic acid, 3-Indoxylsulfuric acid and pipecolic acid. Furthermore, It is possible that TMAO or Trimethylamine (TMA) which is metabolized from TMAO, progress steatosis.

Research Products

• [Journal Article] Hepatocytes release ceramide-enriched pro-inflammatory extracellular vesicles in an IRE1alpha-dependent manner (2016)
  • Author(s): Eiji Kakazu, Amy S. Mauer, Meng Yin and Harmeet Malhi
  • Journal Title: Journal of Lipid Research Volume: 57 Issue: 2 Pages: 233-245
  • DOI: 10.1194/jlr.m063412
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] An imbalance of plasma amino acids in patients with cirrhosis disturbs the tricarboxylic acid cycle of dendritic cell. (2013)
  • Author(s): Kakazu E, Kondo Y, Kogure T, Ninomoiya M, Kimura O, Shimosegawa T
  • Journal Title: Sci Rep. Volume: 2013 Dec 10;3:3459. Issue: 1 Pages: 3459-3459
  • DOI: 10.1038/srep03459
  • Peer Reviewed
• [Journal Article] Supplementation of branched-chain amino acids maintains the serum albumin level in the course of hepatocellular carcinoma recurrence. (2013)
  • Author(s): Kakazu E, Kondo Y, Kogure T, Ninomiya M, Kimura O, Iwata T, Morosawa T, Iwasaki T, Shimosegawa T.
  • Journal Title: The Tohoku Journal of Experimental Medicine Volume: 230 Pages: 191-196
  • NAID: 10031194081
  • Peer Reviewed
• [Presentation] Hepatocytes Release Ceramide-rich Proinflammatory Extracellular Vesicles in an IRE1alpha-dependent manner (2015)
  • Author(s): Eiji Kakazu, Amy S. Mauer, Harmeet Malhi
  • Organizer: アメリカ肝臓学会
  • Place of Presentation: 米国（サンフランシスコ）
  • Year and Date: 2015-11-13
  • Int'l Joint Research
• [Presentation] Metabolomics of hepatic portal blood in Non-alcoholic fatty liver disease mice by capillary electrophoresis time-of-flight mass spectrometry (2015)
  • Author(s): 嘉数英二
  • Organizer: 米国消化器病週間 2015
  • Place of Presentation: ワシントン 米国
  • Year and Date: 2015-05-17 – 2015-05-19
• [Presentation] An imbalance in plasma amino acids of advanced cirrhotic patients suppresses dendritic cells maturation by disturbing the mitochondrial TCA cycle. (2013)
  • Author(s): Eiji Kakazu, Yasuteru Kondo, Takayuki Kogure, Masashi Ninomiya, Osamu Kimura, Tatsuki Morosawa, Tomoaki Iwata, Yoshiyuki Ueno, Tooru Shimosegawa
  • Organizer: Asian Pacific Association for The Study of the Liver
  • Place of Presentation: Suntec City, Singapore
• [Presentation] 肝硬変に出現する血漿アミノ酸不均衡が樹状細胞機能を抑制するメカニズム (2013)
  • Author(s): 嘉数英二、 諸沢 樹、 近藤泰輝、 小暮高之、 二宮匡史、 木村 修、 岩田朋晃、 下瀬川徹
  • Organizer: 第49回日本肝臓学会総会
  • Place of Presentation: 東京
• [Presentation] The tricarboxylic acid (TCA) cycle of dendritic cells was disturbed by imbalance of plasma amino acid observed in cirrhosis. (2013)
  • Author(s): Eiji Kakazu, Yasuteru Kondo, Takayuki Kogure, Masashi Ninomiya, Osamu Kimura, Tatsuki Morosawa, Tomoaki Iwata, Yoshiyuki Ueno, Tooru Shimosegawa
  • Organizer: The American Association for the Study of Liver Diseases
  • Place of Presentation: Washington dc, USA