title: Metformin prevents and reverses inflammation in a non-diabetic mouse model of nonalcoholic steatohepatitis.
abstract: BACKGROUND
  Optimal treatment for nonalcoholic steatohepatitis (NASH) has not yet been established, particularly for individuals without diabetes. We examined the effects of metformin, commonly used to treat patients with type 2 diabetes, on liver pathology in a non-diabetic NASH mouse model.
  
  
  RESULTS
  Eight-week-old C57BL/6 mice were fed a methionine- and choline-deficient plus high fat (MCD+HF) diet with or without 0.1% metformin for 8 weeks. Co-administration of metformin significantly decreased fasting plasma glucose levels, but did not affect glucose tolerance or peripheral insulin sensitivity. Metformin ameliorated MCD+HF diet-induced hepatic steatosis, inflammation, and fibrosis. Furthermore, metformin significantly reversed hepatic steatosis and inflammation when administered after the development of experimental NASH.
  
  
  CONCLUSIONS
  These histological changes were accompanied by reduced hepatic triglyceride content, suppressed hepatic stellate cell activation, and the downregulation of genes involved in fatty acid metabolism, inflammation, and fibrogenesis. Metformin prevented and reversed steatosis and inflammation of NASH in an experimental non-diabetic model without affecting peripheral insulin resistance.
authors.affiliation: Department of Disease Control and Homeostasis, Kanazawa University Graduate School of Medical Science, Ishikawa, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kita
authors.forename: Toshinari
authors.initials: T
authors.lastname: Takamura
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Misu
authors.forename: Tsuguhito
authors.initials: T
authors.lastname: Ota
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Kurita
authors.forename: Yumie
authors.initials: Y
authors.lastname: Takeshita
authors.forename: Masafumi
authors.initials: M
authors.lastname: Uno
authors.forename: Naoto
authors.initials: N
authors.lastname: Matsuzawa-Nagata
authors.forename: Ken-Ichiro
authors.initials: K
authors.lastname: Kato
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ando
authors.forename: Akio
authors.initials: A
authors.lastname: Fujimura
authors.forename: Koji
authors.initials: K
authors.lastname: Hayashi
authors.forename: Toru
authors.initials: T
authors.lastname: Kimura
authors.forename: Yinhua
authors.initials: Y
authors.lastname: Ni
authors.forename: Toshiki
authors.initials: T
authors.lastname: Otoda
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Miyamoto
authors.forename: Yoh
authors.initials: Y
authors.lastname: Zen
authors.forename: Yasuni
authors.initials: Y
authors.lastname: Nakanuma
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kaneko
mesh_terms: D000818:Animals; D016000:Cluster Analysis; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D053263:Gene Regulatory Networks; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000378:metabolism; D006505:Hepatitis / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control; D050356:Lipid Metabolism / Q000187:drug effects; D008103:Liver Cirrhosis / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control; D008687:Metformin / Q000008:administration & dosage / Q000627:therapeutic use*; D051379:Mice; D016688:Mice, Inbred NOD; D065626:Non-alcoholic Fatty Liver Disease; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D008687:Metformin