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

Autor(en)
Cheng Jun Jin, Anna Janina Engstler, Doreen Ziegenhardt, Stephan C Bischoff, Christian Trautwein, Ina Bergheim
Abstrakt

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.

Organisation(en)
Externe Organisation(en)
Friedrich-Schiller-Universität Jena, Universität Hohenheim, Universitätsklinikum Aachen
Journal
Jacobs Journal of Gastroenterology and Hepatology
Band
32
Seiten
708-715
Anzahl der Seiten
8
DOI
https://doi.org/10.1111/jgh.13488
Publikationsdatum
03-2017
Peer-reviewed
Ja
ÖFOS 2012
303009 Ernährungswissenschaften
Schlagwörter
Link zum Portal
https://ucris.univie.ac.at/portal/de/publications/loss-of-lipopolysaccharidebinding-protein-attenuates-the-development-of-dietinduced-nonalcoholic-fatty-liver-disease-in-mice(7a8a8644-5547-4b9f-8574-fda58e1e865a).html