title: Ezetimibe reduces fatty acid quantity in liver and decreased inflammatory cell infiltration and improved NASH in medaka model.
abstract: OBJECTIVE
  We previously developed medaka non-alcoholic steatohepatitis (NASH) model. The model showed similar histology with human NASH so we analyzed the effect of drug using medaka NASH activity score (MNAS). In this study we analyzed the effect of ezetimibe, a small intestine cholesterol transporter inhibitor, on NASH.
  
  
  METHODS
  Medaka NASH model showed steatohepatits with infiltration of D-PAS positive inflammatory cell. In this study we induced medaka NASH and compared the effect of ezetimibe on medaka NASH by HFD.
  
  
  RESULTS
  As compared with the HFD group, ezetimibe reduced total cholesterol and triacyglycerol in the blood. But concerning with liver quantity of fatty acids in the liver were significantly decreased by ezetimibe. Genes related with fatty acid metabolism in liver was also decreased by ezetimibe administration. On histological observations of the liver, increases in the number of inflammatory cells and MNAS were inhibited. With this decrease of fatty acid in liver, medaka NASH was improved by ezetimibe.
  
  
  CONCLUSIONS
  Ezetimibe was clarified as a useful drug to improve NASH.
authors.affiliation: Department of Gastroenterology & Hepatology, Yamaguchi University, Graduated School of Medicine, Minami Kogushi 1-1-1, Ube, Yamaguchi 755-8505, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Oishi
authors.forename: Shuji
authors.initials: S
authors.lastname: Terai
authors.forename: Shinya
authors.initials: S
authors.lastname: Kuwashiro
authors.forename: Koichi
authors.initials: K
authors.lastname: Fujisawa
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nishina
authors.forename: Isao
authors.initials: I
authors.lastname: Sakaida
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D001384:Azetidines / Q000627:therapeutic use*; D004195:Disease Models, Animal; D000069438:Ezetimibe; D005227:Fatty Acids / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D005234:Fatty Liver / Q000188:drug therapy* / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease; D009990:Oryzias
chemical_list: D000924:Anticholesteremic Agents; D001384:Azetidines; D005227:Fatty Acids; D000069438:Ezetimibe