title: Role of the inducible nitric oxide synthase in the onset of fructose-induced steatosis in mice.
abstract: To test the hypothesis that the inducible nitric oxide synthase (iNOS) is involved in mediating the toll-like receptor 4-dependent effects on the liver in the onset of fructose-induced steatosis, wild-type and iNOS knockout (iNOS(-/-)) mice were either fed tap water or 30% fructose solution for 8 weeks. Chronic consumption of 30% fructose solution led to a significant increase in hepatic steatosis and inflammation as well as plasma alanine-aminotransferase levels in wild-type mice. This effect of fructose feeding was markedly attenuated in iNOS(-/-) mice. Hepatic lipidperoxidation, concentration of phospho-IκB, nuclear factor κB activity, and tumor necrosis factor-α mRNA level were significantly increased in fructose-fed wild-type mice, whereas in livers of fructose-fed iNOS(-/-) mice, lipidperoxidation, phospho-IκB, nuclear factor κB activity, and tumor necrosis factor-α expression were almost at the level of controls. However, portal endotoxin levels and hepatic myeloid differentiation factor 88 expression were significantly higher in both fructose-fed groups compared to controls. Taken together, these data suggest that (i) the formation of reactive oxygen species in liver is a key factor in the onset of fatty liver and (ii) iNOS is involved in mediating the endotoxin/toll-like receptor 4-dependent effects in the development of fructose-induced fatty liver.
authors.affiliation: Department of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany.
authors.forename: Astrid
authors.initials: A
authors.lastname: Spruss
authors.forename: Giridhar
authors.initials: G
authors.lastname: Kanuri
authors.forename: Kirsten
authors.initials: K
authors.lastname: Uebel
authors.forename: Stephan C
authors.initials: SC
authors.lastname: Bischoff
authors.forename: Ina
authors.initials: I
authors.lastname: Bergheim
mesh_terms: D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D018920:Coculture Techniques; D004731:Endotoxins / Q000097:blood; D005234:Fatty Liver / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D005631:Fructokinases / Q000235:genetics / Q000378:metabolism; D005632:Fructose; D005978:Glutathione / Q000378:metabolism; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism; D007333:Insulin Resistance; D007728:Kupffer Cells / Q000378:metabolism / Q000473:pathology; D015227:Lipid Peroxidation; D008099:Liver / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D009929:Organ Size; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D014158:Transcription, Genetic; D014280:Triglycerides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D015430:Weight Gain
chemical_list: D000447:Aldehydes; D004731:Endotoxins; D020672:I-kappa B Proteins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D005632:Fructose; C002744:3-nitrotyrosine; D014443:Tyrosine; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D005631:Fructokinases; C046173:fructokinase; D005978:Glutathione; C027576:4-hydroxy-2-nonenal