title: Lipopolysaccharide-binding protein plasma levels and liver TNF-alpha gene expression in obese patients: evidence for the potential role of endotoxin in the pathogenesis of non-alcoholic steatohepatitis.
abstract: BACKGROUND
  Some lines of evidence suggest that endotoxin may induce non-alcoholic steatohepatitis (NASH) in a background of fatty liver. However, a clear association between increased endotoxemia and development of steatohepatitis in obese patients has not been confirmed. We aim to assess the endotoxemic state of patients with non-alcoholic fatty liver disease (NAFLD) and its relationship with the liver expression of TNF-alpha and the presence of NASH.
  
  
  METHODS
  Prospective study comprising 40 patients with morbid obesity who were diagnosed with NAFLD. Blood samples and liver biopsies were collected. Endotoxemia was assessed by the evaluation of circulating level of LPS-binding protein (LBP). Plasma levels of LBP and TNF-alpha were assessed by ELISA. The expression of TNF-alpha in liver tissue was evaluated by real-time PCR. Histological examination was performed to evaluate the presence of steatosis or NASH.
  
  
  RESULTS
  Levels of LBP were increased in obese patients with NAFLD. In addition, plasma level of LBP was increased in patients with steatohepatitis (14.2 +/- 3.9 microg/mL) when compared with patients with simple steatosis (11.5 +/- 3.2 microg/mL), P=0.041. The TNF-alpha mRNA expression in liver tissue was significantly higher in patients with NASH. This increment correlated with the rise in plasma levels of LBP (r=0.412, P=0.036).
  
  
  CONCLUSIONS
  NAFLD patients have elevated plasma levels of LBP and they are further increased in patients with NASH. This increase is related to a rise in TNF-alpha gene expression in the hepatic tissue which supports a role for endotoxemia in the development of steatohepatitis in obese patients.
authors.affiliation: Gastroenterology Unit, University Hospital Marques de Valdecilla, School of Medicine, Santander, Spain.
authors.forename: Armando Guerra
authors.initials: AG
authors.lastname: Ruiz
authors.forename: Fernando
authors.initials: F
authors.lastname: Casafont
authors.forename: Javier
authors.initials: J
authors.lastname: Crespo
authors.forename: Amalia
authors.initials: A
authors.lastname: Cayón
authors.forename: Marta
authors.initials: M
authors.lastname: Mayorga
authors.forename: Angel
authors.initials: A
authors.lastname: Estebanez
authors.forename: José Carlos
authors.initials: JC
authors.lastname: Fernadez-Escalante
authors.forename: Fernando
authors.initials: F
authors.lastname: Pons-Romero
mesh_terms: D000209:Acute-Phase Proteins; D000328:Adult; D015904:Biliopancreatic Diversion; D002352:Carrier Proteins / Q000097:blood*; D004731:Endotoxins / Q000502:physiology*; D005234:Fatty Liver / Q000235:genetics*; D015870:Gene Expression / Q000502:physiology*; D005786:Gene Expression Regulation; D006505:Hepatitis / Q000235:genetics*; D006801:Humans; D008099:Liver / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000097:blood*; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D009767:Obesity, Morbid / Q000235:genetics* / Q000601:surgery; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D000099231:Lipopolysaccharide-Binding Protein
chemical_list: D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D004731:Endotoxins; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D000099231:Lipopolysaccharide-Binding Protein