title: Treatment with alpha-galactosylceramide protects mice from early onset of nonalcoholic steatohepatitis: Role of intestinal barrier function.
abstract: The role of invariant natural killer T cells in the development of nonalcoholic steatohepatitis (NASH) has not yet been fully understood. Here, the effect of the invariant natural killer T-cell activator alpha-galactosylceramide (αGalCer) on the development of nonalcoholic fatty liver disease and intestinal barrier function was assessed in a mouse model of early Western-style diet (WSD) induced NASH.
  
  
  
  Female C57BL/6J mice were either fed a liquid control diet or a liquid fructose-enriched WSD for 6 wk while being treated three times weekly with αGalCer (2 μg intraperitoneal) or vehicle. Indices of liver damage, glucose metabolism, and intestinal permeability were measured. Treatment with αGalCer markedly suppressed hepatic fat accumulation and inflammation while not affecting fasting glucose. The protective effects of αGalCer were associated with a protection against the increased translocation of bacterial endotoxins and the decreased protein levels of tight junction proteins occludin and zonula occludens 1 found in vehicle-treated mice while being fed a WSD.
  
  
  
  Taken together, our data suggest that the protective effects of αGalCer against the development of a diet-induced NASH in mice are associated with a protection against the increased translocation of intestinal bacterial endotoxins associated with the development of NASH.
authors.affiliation: Institute of Nutrition, SD Model Systems of Molecular Nutrition, Friedrich-Schiller University of Jena, Jena, Germany.
authors.forename: Anna Janina
authors.initials: AJ
authors.lastname: Engstler
authors.affiliation: Institute of Nutrition, SD Model Systems of Molecular Nutrition, Friedrich-Schiller University of Jena, Jena, Germany.
authors.forename: Cathrin
authors.initials: C
authors.lastname: Sellmann
authors.affiliation: Institute of Nutrition, SD Model Systems of Molecular Nutrition, Friedrich-Schiller University of Jena, Jena, Germany.
authors.forename: Cheng Jun
authors.initials: CJ
authors.lastname: Jin
authors.affiliation: Department of Nutritional Sciences, Molecular Nutritional Science, University of Vienna, Vienna, Austria.
authors.forename: Annette
authors.initials: A
authors.lastname: Brandt
authors.affiliation: Institute of Nutrition, SD Model Systems of Molecular Nutrition, Friedrich-Schiller University of Jena, Jena, Germany.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Herz
authors.affiliation: Institute of Nutrition, SD Model Systems of Molecular Nutrition, Friedrich-Schiller University of Jena, Jena, Germany.
authors.forename: Josephine
authors.initials: J
authors.lastname: Priebs
authors.affiliation: Institute of Nutrition, SD Model Systems of Molecular Nutrition, Friedrich-Schiller University of Jena, Jena, Germany.|Department of Nutritional Sciences, Molecular Nutritional Science, University of Vienna, Vienna, Austria.
authors.forename: Ina
authors.initials: I
authors.lastname: Bergheim
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D066273:Diet, Western / Q000009:adverse effects; D004195:Disease Models, Animal; D004731:Endotoxins / Q000633:toxicity; D005260:Female; D005699:Galactosylceramides / Q000494:pharmacology*; D007371:Interferon-gamma / Q000378:metabolism; D007422:Intestines / Q000382:microbiology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D055611:Natural Killer T-Cells; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy* / Q000209:etiology; D062793:Occludin / Q000235:genetics / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology*; D062725:Tight Junction Proteins / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014280:Triglycerides / Q000097:blood; D062826:Zonula Occludens-1 Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; D004731:Endotoxins; D005699:Galactosylceramides; D062793:Occludin; D020011:Protective Agents; D062725:Tight Junction Proteins; D016212:Transforming Growth Factor beta; D014280:Triglycerides; D062826:Zonula Occludens-1 Protein; C493154:alpha-galactosylceramide; C544013:alpha-smooth muscle actin, mouse; D007371:Interferon-gamma; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase
keywords: Endotoxin; Natural killer T cells; Small intestine; Tight junction proteins; Western-style diet