en
Scientific article
English

Fat diet and alcohol-induced steatohepatitis after LPS challenge in mice: role of bioactive TNF and Th1 type cytokines

Published inCytokine, vol. 44, no. 1, p. 118-125
Publication date2008
Abstract

Obesity with insulin resistance and alcohol are the most frequent causes of steatohepatitis. This work investigates the contribution of bioactive TNF and Th1 type cytokines in a mouse model of steatohepatitis induced by FAT alone or FAT+EtOH and endotoxin. The extent of liver injury and cytokine activation induced by endotoxin in chronic FAT-fed mice, FAT+EtOH-fed mice, or mice fed standard chow were analyzed. Endotoxin administration to either FAT-fed or FAT+EtOH-fed mice increased serum ALT and AST compared to standard chow mice. Immunoreactive TNF was strongly activated by LPS in FAT-fed and FAT+EtOH-fed mice which presented the highest levels, but low levels were found in standard chow mice. In contrast, bioactive TNF was only present in serum of FAT-fed and in particular the highest levels were found in FAT+EtOH-fed mice. Moreover, soluble TNFR2 but not TNFR1 was found in lower amounts in serum of FAT+EtOH-fed mice compared to FAT-fed mice. Steatohepatitis was associated with increased IL-6, IFN-gamma, and iNOS mRNA and proteins. Data show that a moderately FAT diet and low-dose EtOH concur to generate steatohepatitis and TNF liver expression after LPS. In this model, changes in the regulation of TNF are associated with increased expression of IL-6, IFN-gamma, and iNOS.

Keywords
  • Animals
  • Cytokines/physiology
  • Dietary Fats/pharmacology
  • Disease Models, Animal
  • Enzyme Activation
  • Ethanol/adverse effects
  • Fatty Liver/etiology/pathology
  • Fatty Liver, Alcoholic/pathology/physiopathology
  • Female
  • Interferon-gamma/physiology
  • Interleukin-12 Subunit p40/physiology
  • Interleukin-6/physiology
  • Lipopolysaccharides
  • Liver/cytology
  • Mice
  • Mice, Inbred C57BL
  • Neutrophil Infiltration
  • Nitric Oxide Synthase Type II/metabolism
  • Peroxidase/metabolism
  • RNA, Messenger/metabolism
  • Th1 Cells/immunology
  • Tumor Necrosis Factor-alpha/physiology
Citation (ISO format)
OLLEROS, Maria-Luisa et al. Fat diet and alcohol-induced steatohepatitis after LPS challenge in mice: role of bioactive TNF and Th1 type cytokines. In: Cytokine, 2008, vol. 44, n° 1, p. 118–125. doi: 10.1016/j.cyto.2008.07.001
Main files (1)
Article (Accepted version)
accessLevelRestricted
Identifiers
ISSN of the journal1096-0023
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