title: The Selective SGLT2 Inhibitor Ipragliflozin Has a Therapeutic Effect on Nonalcoholic Steatohepatitis in Mice.
abstract: OBJECTIVE
  In recent years, nonalcoholic steatohepatitis (NASH) has become a considerable healthcare burden worldwide. Pathogenesis of NASH is associated with type 2 diabetes mellitus (T2DM) and insulin resistance. However, a specific drug to treat NASH is lacking. We investigated the effect of the selective sodium glucose cotransporter 2 inhibitor (SGLT2I) ipragliflozin on NASH in mice.
  
  
  METHODS
  We used the Amylin liver NASH model (AMLN), which is a diet-induced model of NASH that results in obesity and T2DM. AMLN mice were fed an AMLN diet for 20 weeks. SGLT2I mice were fed an AMLN diet for 12 weeks and an AMLN diet with 40 mg ipragliflozin/kg for 8 weeks.
  
  
  RESULTS
  AMLN mice showed steatosis, inflammation, and fibrosis in the liver as well as obesity and insulin resistance, features that are recognized in human NASH. Ipragliflozin improved insulin resistance and liver injury. Ipragliflozin decreased serum levels of free fatty acids, hepatic lipid content, the number of apoptotic cells, and areas of fibrosis; it also increased lipid outflow from the liver.
  
  
  CONCLUSIONS
  Ipragliflozin improved the pathogenesis of NASH by reducing insulin resistance and lipotoxicity in NASH-model mice. Our results suggest that ipragliflozin has a therapeutic effect on NASH with T2DM.
authors.affiliation: Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Honda
authors.affiliation: Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Kento
authors.initials: K
authors.lastname: Imajo
authors.affiliation: Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kato
authors.affiliation: Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Takaomi
authors.initials: T
authors.lastname: Kessoku
authors.affiliation: Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ogawa
authors.affiliation: Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Tomeno
authors.affiliation: Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Kato
authors.affiliation: Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Mawatari
authors.affiliation: Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Fujita
authors.affiliation: Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Yoneda
authors.affiliation: Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Saito
authors.affiliation: Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nakajima
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D004195:Disease Models, Animal; D005960:Glucosides / Q000627:therapeutic use*; D007004:Hypoglycemic Agents; D007333:Insulin Resistance; D051379:Mice; D065626:Non-alcoholic Fatty Liver Disease / Q000150:complications / Q000188:drug therapy*; D009765:Obesity / Q000150:complications*; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013876:Thiophenes / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D005960:Glucosides; D007004:Hypoglycemic Agents; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013876:Thiophenes; C572941:ipragliflozin