title: The pro-inflammatory action of tumour necrosis factor-α in non-alcoholic steatohepatitis is independent of the NSMAF gene product.
abstract: BACKGROUND
  The role of tumour necrosis factor-α (TNF-α) in the development of non-alcoholic steatohepatitis remains unclear.
  
  
  OBJECTIVE
  We evaluated the role of TNF-α and NSMAF gene product factor associated with neutral sphingomyelinase activation, a protein adaptor of the TNF-α receptor-1, in a mouse model of non-alcoholic steatohepatitis.
  
  
  METHODS
  Mice deficient either for TNF-α or factor associated with neutral sphingomyelinase activation, as well as control animals, were fed a methionine and choline-deficient diet for 5 weeks. Liver histology, serum glucose, triglycerides, cholesterol and alanine aminotransferase levels were compared between groups.
  
  
  RESULTS
  Weight loss, decrease of serum triglyceride and glucose levels and increase of alanine aminotransferase levels were attenuated in TNF(-/-) mice. Similarly, we found a significantly lower lobular inflammation in TNF(-/-) mice. Liver expression of transforming growth factor-β, peroxisome proliferator-activated receptor-γ(1, 2) and monocyte chemoattractant protein-1 was attenuated in TNF(-/-) mice. In addition, the phosphatidylcholine/phosphatidylethanolamine liver ratio decrease was less important in TNF(-/-) mice. The increase in hepatic sphingomyelin and ceramide levels was less pronounced in TNF(-/-) animals.
  
  
  CONCLUSIONS
  Whereas TNF-α modulates the inflammatory process that underlies methionine and choline-deficient diet-induced non-alcoholic steatohepatitis, its effects are not mediated by factor associated with neutral sphingomyelinase activation. Whether changes in liver lipids, like phosphatidylcholine and ceramide, are causally involved in tumour necrosis factor-mediated liver inflammation remains an open issue.
authors.affiliation: INSERM U1043, Toulouse F-31300, France. mas.e@chu-toulouse.fr
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Mas
authors.forename: Marie
authors.initials: M
authors.lastname: Danjoux
authors.forename: Virginie
authors.initials: V
authors.lastname: Garcia
authors.forename: Stéphane
authors.initials: S
authors.lastname: Carpentier
authors.forename: Bruno
authors.initials: B
authors.lastname: Ségui
authors.forename: Thierry
authors.initials: T
authors.lastname: Levade
mesh_terms: D000818:Animals; D002794:Choline / Q000378:metabolism; D002796:Choline Deficiency / Q000150:complications; D004032:Diet / Q000009:adverse effects; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000378:metabolism* / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008715:Methionine / Q000172:deficiency; D051379:Mice; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease; D060888:Real-Time Polymerase Chain Reaction; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C491112:Nsmaf protein, mouse; D014409:Tumor Necrosis Factor-alpha; D008715:Methionine; D013108:Sphingomyelin Phosphodiesterase; D002794:Choline