Loss of lipopolysaccharide-binding protein attenuates the development of diet-induced non-alcoholic fatty liver disease in mice

Autoren:Jin, Cheng Jun (Friedrich-Schiller-Universität Jena); Engstler, Anna Janina (Friedrich-Schiller-Universität Jena); Ziegenhardt, Doreen (Friedrich-Schiller-Universität Jena); Bischoff, Stephan C (Universität Hohenheim); Trautwein, Christian (Universitätsklinikum Aachen); Bergheim, Ina (Friedrich-Schiller-Universität Jena)

BACKGROUND AND AIM: 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.

CONCLUSION: Taken together, our results suggest that LBP is a critical factor in the development of non-alcoholic fatty liver disease in mice.

Anzahl der Seiten:8
Journaltitel:Jacobs Journal of Gastroenterology and Hepatology
Peer reviewed:true
Digital Object Identifier (DOI):http://dx.doi.org/10.1111/jgh.13488
Bibliographische Notiz:© 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.