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

Guerra Ruiz, Armando MSc
Casafont, Fernando MD
Crespo, Javier MD
Cayón, Amalia PhD
Mayorga, Marta MD
Estebanez, Angel Laboratory Technician
Fernadez-Escalante, José Carlos MD
Pons-Romero, Fernando MD

¹Gastroenterology Unit, University Hospital “Marques de Valdecilla” School of Medicine, Santander, Spain
²Department of Pathology, University Hospital “Marques de Valdecilla” School of Medicine, Santander, Spain
³Department of Surgery, University Hospital “Marques de Valdecilla” School of Medicine, Santander, Spain
⁴Gastroenterology Unit, Hospital “Marques de Valdecilla”, Avda Valdecilla s/n, 39008 Santander, Spain

Received: 15 February 2007/Accepted: 12 April 2007/Published online: 14 November 2007

Obesity Surgery 17(10):p 1374-1380, October 2007. | DOI: 10.1007/s11695-007-9243-7

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-α 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-α were assessed by ELISA. The expression of TNF-α 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 μg/mL) when compared with patients with simple steatosis (11.5 ±3.2 μg/mL),P=0.041.The TNF-α 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).

Conclusion

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-α gene expression in the hepatic tissue which supports a role for endotoxemia in the development of steatohepatitis in obese patients.