title: Effect of miglitol on the suppression of nonalcoholic steatohepatitis development and improvement of the gut environment in a rodent model.
abstract: BACKGROUND
  The gut environment has been considered to play a role in the development of nonalcoholic steatohepatitis (NASH). α-glucosidase inhibitors (α-GIs) delay carbohydrate absorption and may change the gut environment. We considered that the protective effect of α-GIs against NASH development is related to changes in the gut environment and thus investigated the effects of miglitol, an α-GI, on NASH development and the gut environment.
  
  
  METHODS
  Mice were divided into three groups and fed a normal chow diet (NCD), a high-fat high-sucrose diet (HFHSD), or HFHSD plus 0.04% miglitol (HFHSD plus M) for 12 weeks.
  
  
  RESULTS
  Insulin resistance developed more in the HFHSD group than in the NCD group, whereas it was suppressed in the HFHSD plus M group. NASH was evaluated histologically, biochemically, and on the basis of messenger RNA expression levels. Miglitol treatment suppressed HFHSD-induced NASH development with the suppression of hepatic Toll-like receptor 4 expression, increased glucagon-like peptide 1 (GLP-1) concentration, and reduced lipopolysaccharide concentration in portal plasma. Regarding the gut environment, the intestinal transit time was shortened and colon inflammation was suppressed in the HFHSD plus M group compared with the HFHSD group. Regarding the gut microbiota, the abundances of Erysipelotrichaceae and Coriobacteriaceae were increased in the HFHSD group compared with the NCD group, whereas the increase was suppressed in the HFHSD plus M group.
  
  
  CONCLUSIONS
  We demonstrated that miglitol has a protective effect against HFHSD-induced NASH development. The increased GLP-1 secretion and the suppression of endotoxemia, associated with the changes in the gut environment, including the gut microbiota, could contribute to the underlying mechanisms.
authors.affiliation: Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Kishida
authors.affiliation: Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Okubo
authors.affiliation: Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
authors.forename: Haruya
authors.initials: H
authors.lastname: Ohno
authors.affiliation: Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Oki
authors.affiliation: Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan. masayone17@hiroshima-u.ac.jp.
authors.forename: Masayasu
authors.initials: M
authors.lastname: Yoneda
mesh_terms: D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D000069196:Gastrointestinal Microbiome; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D065089:Glycoside Hydrolase Inhibitors / Q000494:pharmacology*; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease / Q000382:microbiology / Q000517:prevention & control*
chemical_list: D065089:Glycoside Hydrolase Inhibitors; C045621:miglitol; D017485:1-Deoxynojirimycin; D052216:Glucagon-Like Peptide 1
keywords: Glucagon-like peptide 1; Gut microbiota; Inflammation; Miglitol; Nonalcoholic steatohepatitis