Cheng Jun Jin1, Anna Janina Engstler1, Doreen Ziegenhardt1, Stephan C Bischoff2, Christian Trautwein3, Ina Bergheim1. 1. Institute of Nutritional Sciences, SD Model Systems of Molecular Nutrition, Friedrich-Schiller-University Jena, Jena, Germany. 2. Department of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany. 3. Department of Gastroenterology, Metabolic Diseases and Internal Intensive Medicine (Med. Clinic III), University Hospital RWTH Aachen, Aachen, Germany.
Abstract
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.
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.
Authors: Luis Fontana; Julio Plaza-Díaz; Paula Robles-Bolívar; Héctor Valente-Godínez; María José Sáez-Lara; Francisco Abadía-Molina; Carolina Gómez-Llorented; Ángel Gil; Ana I Álvarez-Mercado Journal: Nutrients Date: 2021-01-11 Impact factor: 5.717
Authors: Annette Brandt; Anika Nier; Cheng Jun Jin; Anja Baumann; Finn Jung; Vicent Ribas; Carmen García-Ruiz; Jose C Fernández-Checa; Ina Bergheim Journal: Redox Biol Date: 2018-12-23 Impact factor: 11.799