title: Metabolomics-based search for therapeutic agents for non-alcoholic steatohepatitis.
abstract: BACKGROUND
  Non-alcoholic fatty liver disease (NAFLD) is the commonest form of chronic liver disease in developed countries. Non-alcoholic steatohepatitis (NASH), which represents advanced stage NAFLD, is increasingly being recognized as a major cause of liver-related morbidity and mortality. However, no effective drugs against NASH have yet been developed. Therefore, we searched for candidate therapeutic agents based on the changes in levels of hepatic metabolites via gas chromatography mass spectrometry (GC/MS)-based metabolome analysis of livers from methionine-choline deficient (MCD) diet-fed mice, a mouse model of NASH.
  
  
  METHODS
  The metabolites were extracted from the livers of the MCD diet-fed mice and then analyzed using GC/MS. Subsequently, the MCD diet-fed mice were supplemented with hypotaurine, and the therapeutic effects of hypotaurine against steatohepatitis were evaluated.
  
  
  RESULTS
  Ninety-nine metabolites were detected in the livers of the MCD diet-induced steatohepatitis model mice. Among these metabolites, hypotaurine exhibited the greatest decrease in its concentration in the mice. Supplementation with 2 mmol/kgBW hypotaurine attenuated liver injuries and fat accumulation caused by the MCD diet-induced steatohepatitis. Furthermore, 10 mmol/kgBW hypotaurine supplementation ameliorated fibrosis and oxidative stress induced by the MCD diet.
  
  
  CONCLUSIONS
  The present metabolome analysis-based study demonstrated that hypotaurine is a novel candidate therapeutic agent for NASH.
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chu-o-ku, Kobe, Hyogo 650-0017, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Terashima
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chu-o-ku, Kobe, Hyogo 650-0017, Japan. Electronic address: nishiums@med.kobe-u.ac.jp.
authors.forename: Shin
authors.initials: S
authors.lastname: Nishiumi
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chu-o-ku, Kobe, Hyogo 650-0017, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Minami
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chu-o-ku, Kobe, Hyogo 650-0017, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kawano
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chu-o-ku, Kobe, Hyogo 650-0017, Japan.
authors.forename: Namiko
authors.initials: N
authors.lastname: Hoshi
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chu-o-ku, Kobe, Hyogo 650-0017, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Azuma
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chu-o-ku, Kobe, Hyogo 650-0017, Japan; The Integrated Center for Mass Spectrometry, Kobe University Graduate School of Medicine, 7-5-1 Chu-o-ku, Kusunoki-cho, Kobe, Hyogo 650-0017, Japan; Division of Metabolomics Research, Kobe University Graduate School of Medicine, 7-5-1 Chu-o-ku, Kusunoki-cho, Kobe, Hyogo 650-0017, Japan. Electronic address: myoshida@med.kobe-u.ac.jp.
authors.forename: Masaru
authors.initials: M
authors.lastname: Yoshida
mesh_terms: D000818:Animals; D002794:Choline / Q000008:administration & dosage; D004032:Diet; D005234:Fatty Liver / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000473:pathology; D008297:Male; D055442:Metabolome; D008715:Methionine / Q000172:deficiency; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease; D009765:Obesity / Q000188:drug therapy / Q000378:metabolism; D018384:Oxidative Stress; D013654:Taurine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism / Q000627:therapeutic use
chemical_list: D013654:Taurine; C003949:hypotaurine; D008715:Methionine; D002794:Choline
keywords: GC/MS; Hypotaurine; Metabolome analysis; NASH