title: Loss of lipopolysaccharide-binding protein attenuates the development of diet-induced non-alcoholic fatty liver disease in mice.
abstract: OBJECTIVE
  It has been suggested in several studies that an increased translocation of bacterial lipopolysaccharide (LPS) and, subsequently, an activation of toll-like receptor (TLR)-dependent signaling pathways in the liver may contribute to the development of non-alcoholic fatty liver disease.
  
  
  METHODS
  Eight-week-old lipopolysaccharide-binding protein (LBP)-/- and wild-type (WT) mice were pair fed either a liquid diet rich in fat, fructose, and cholesterol (Western-style diet [WSD]) or a control liquid diet for 8 weeks. Parameters of liver injury, markers of TLR-4-dependent signaling pathway, and glucose/lipid metabolism were determined.
  
  
  RESULTS
  Despite similar total caloric intake, weight gain, fasting blood glucose levels, and liver-to-bodyweight ratio, indices of liver damage determined by liver histology and transaminases were markedly lower in WSD-fed LBP-/- mice than in WSD-fed WT animals. In line with these findings, number of neutrophils, F4/80 positive cells, and plasminogen activator inhibitor 1 were only found to be significantly increased in livers of WSD-fed WT mice. While mRNA expressions of TLR-4 and myeloid differentiation primary response 88 were similar between WSD-fed groups, concentrations of inducible nitric oxide synthase protein and 4-hydroxynonenal protein adducts were significantly higher in livers of WSD-fed WT mice than in WSD-fed LBP-/- animals. Markers of lipid metabolism, for example, sterol regulatory element-binding protein 1c and fatty acid synthase per se, were significantly lower in livers of LBP-/- mice; however, mRNA expressions did not differ between controls and WSD-fed mice within the respective mouse strain.
  
  
  CONCLUSIONS
  Taken together, our results suggest that LBP is a critical factor in the development of non-alcoholic fatty liver disease in mice.
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: Anna Janina
authors.initials: AJ
authors.lastname: Engstler
authors.affiliation: Institute of Nutritional Sciences, SD Model Systems of Molecular Nutrition, Friedrich-Schiller-University Jena, Jena, Germany.
authors.forename: Doreen
authors.initials: D
authors.lastname: Ziegenhardt
authors.affiliation: Department of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany.
authors.forename: Stephan C
authors.initials: SC
authors.lastname: Bischoff
authors.affiliation: Department of Gastroenterology, Metabolic Diseases and Internal Intensive Medicine (Med. Clinic III), University Hospital RWTH Aachen, Aachen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Trautwein
authors.affiliation: Institute of Nutritional Sciences, SD Model Systems of Molecular Nutrition, Friedrich-Schiller-University Jena, Jena, Germany.
authors.forename: Ina
authors.initials: I
authors.lastname: Bergheim
mesh_terms: D000209:Acute-Phase Proteins / Q000172:deficiency* / Q000502:physiology*; D000818:Animals; D002352:Carrier Proteins / Q000502:physiology*; D004195:Disease Models, Animal; D005947:Glucose / Q000378:metabolism; D050356:Lipid Metabolism; D008070:Lipopolysaccharides / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000172:deficiency* / Q000502:physiology*; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D065626:Non-alcoholic Fatty Liver Disease / Q000209:etiology* / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology; D051193:Toll-Like Receptors / Q000378:metabolism; D000099231:Lipopolysaccharide-Binding Protein
chemical_list: D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D005947:Glucose; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D051193:Toll-Like Receptors; D000099231:Lipopolysaccharide-Binding Protein
keywords: LBP; NAFLD; endotoxin; iNOS