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.
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.
Ruiz
Armando Guerra
AG
Gastroenterology Unit, University Hospital Marques de Valdecilla, School of Medicine, Santander, Spain.
Casafont
Fernando
F
Crespo
Javier
J
Cayón
Amalia
A
Mayorga
Marta
M
Estebanez
Angel
A
Fernadez-Escalante
José Carlos
JC
Pons-Romero
Fernando
F
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
D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D004731:Endotoxins; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D000099231:Lipopolysaccharide-Binding Protein