title: Oral Glutamine Supplementation Protects Female Mice from Nonalcoholic Steatohepatitis.
abstract: BACKGROUND
  Genetic factors, a diet rich in fat and sugar, and an impaired intestinal barrier function are critical in the development of nonalcoholic steatohepatitis (NASH). The nonessential amino acid glutamine (Gln) has been suggested to have protective effects on intestinal barrier function but also against the development of liver diseases of various etiologies.
  
  
  OBJECTIVE
  The effect of oral Gln supplementation on the development of Western-style diet (WSD)-induced NASH in mice was assessed.
  
  
  METHODS
  Female 6- to 8-wk-old C57BL/6J mice were pair-fed a control (C) diet or a WSD alone or supplemented with 2.1 g l-Gln/kg body weight for 6 wk (C+Gln or WSD+Gln). Indexes of liver damage, lipid peroxidation, and glucose metabolism and endotoxin concentrations were measured.
  
  
  RESULTS
  Although Gln supplementation had no effect on the loss of the tight junction protein occludin, the increased portal endotoxin and fasting glucose concentrations found in WSD-fed mice, markers of liver damage (e.g., nonalcoholic fatty liver disease activity score and number of neutrophils in the liver) were significantly lower in the WSD+Gln group than in the WSD group (~47% and ~60% less, respectively; P < 0.05). Concentrations of inducible nitric oxide synthase (iNOS) protein and 3-nitrotyrosin protein adducts were significantly higher in livers of WSD-fed mice than in all other groups (~8.6- and ~1.9-fold higher, respectively, compared with the C group; P < 0.05) but did not differ between WSD+Gln-, C-, and C+Gln-fed mice. Hepatic tumor necrosis factor α and plasminogen activator inhibitor 1 concentrations were significantly higher in WSD-fed mice (~1.6- and ~1.8-fold higher, respectively; P < 0.05) but not in WSD+Gln-fed mice compared with C mice.
  
  
  CONCLUSIONS
  Our data suggest that the protective effects of oral Gln supplementation on the development of WSD-induced NASH in mice are associated with protection against the induction of iNOS and lipid peroxidation in the liver.
authors.affiliation: Institute of Nutritional Sciences, SD Model Systems of Molecular Nutrition, Friedrich-Schiller University Jena, Jena, Germany;
authors.forename: Cathrin
authors.initials: C
authors.lastname: Sellmann
authors.affiliation: Institute of Nutritional Sciences, SD Model Systems of Molecular Nutrition, Friedrich-Schiller University Jena, Jena, Germany;
authors.forename: Cheng Jun
authors.initials: CJ
authors.lastname: Jin
authors.affiliation: Institute of Nutritional Sciences, SD Model Systems of Molecular Nutrition, Friedrich-Schiller University Jena, Jena, Germany;
authors.forename: Christian
authors.initials: C
authors.lastname: Degen
authors.affiliation: Nutrition Biology Laboratory EA4466, Faculty of Pharmacy, Paris Descartes University, Sorbonne Paris Cité, Paris, France; and Clinical Chemistry Department, Paris Center University Hospitals, Public Assistance Hospitals of Paris, Paris, France.
authors.forename: Jean-Pascal
authors.initials: JP
authors.lastname: De Bandt
authors.affiliation: Institute of Nutritional Sciences, SD Model Systems of Molecular Nutrition, Friedrich-Schiller University Jena, Jena, Germany; ina.bergheim@uni-jena.de.
authors.forename: Ina
authors.initials: I
authors.lastname: Bergheim
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D066273:Diet, Western / Q000009:adverse effects; D019587:Dietary Supplements; D004386:Duodenum / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004731:Endotoxins / Q000097:blood; D005260:Female; D005973:Glutamine / Q000627:therapeutic use*; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015227:Lipid Peroxidation; D008099:Liver / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D008810:Mice, Inbred C57BL; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D065626:Non-alcoholic Fatty Liver Disease / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism; D011972:Receptor, Insulin / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D013047:Specific Pathogen-Free Organisms; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D004731:Endotoxins; D017395:Plasminogen Activator Inhibitor 1; D014409:Tumor Necrosis Factor-alpha; D005973:Glutamine; C002744:3-nitrotyrosine; D014443:Tyrosine; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D011972:Receptor, Insulin
keywords: glutamine; hepatic inflammation; iNOS; nonalcoholic steatohepatitis; reactive oxygen species