Z Gastroenterol 2006; 44 - A10
DOI: 10.1055/s-2006-955551

Visfatin in the immunopathogenesis of liver disease

AR Moschen 1, B Enrich 1, HC Santner 1, H Niederegger 2, PL Moser 3, H Tilg 1
  • 1Department of Medicine, Clinical Division of Gastroenterology and Hepatology
  • 2Innsbruck Biocentre, Division of Experimental Pathophysiology and Immunology
  • 3Institute of Pathology, Innsbruck Medical University, Innsbruck, Austria

Aims: Adipose tissue is no longer considered to be an inert tissue functioning solely as energy storage but is emerging as a key factor in the regulation of many pathologic processes especially immune functions. Adipocytokines – adipocyte-derived mediators – such as leptin and adiponectin are involved in liver inflammation. In the present study we focused on the role of the recently described adipocytokine visfatin in the immunopathogenesis of liver disease.

Methods: In vitro, visfatin regulation under inflammatory conditions was determined in the human HepG2 hepatoma cell line. Human serum samples of patients with chronic liver disease (CLD) (n=78; 42: alcoholic, 36: viral) and healthy controls (n=48 healthy) were assayed for visfatin by enzyme immuno assay. Cryo sections from liver biopsy specimens were analyzed by immunofluorescence. In vivo, we investigated visfatin expression in normal, healthy murine liver tissue and under inflammatory conditions in experimentally ConA-induced hepatitis.

Results: Pro-inflammatory cytokines such as IL-1β, IL-6 and TNFα dose-dependently up-regulated visfatin mRNA expression in human HepG2s. In patients with CLD serum visfatin levels were significantly elevated compared to control subjects. Among CLD patients visfatin levels were higher in patients with a viral compared to those with alcoholic disease etiology. As determined by immunofluorescence double-staining visfatin was detected by hepatocytes, sinusoidal endothelial cell, and Kupffer cells but not in hepatic stellate cells. In vivo, visfatin was readily detectable in healthy murine liver. Induction of ConA-induced acute liver failure resulted in a 10.8-fold increase of hepatic visfatin mRNA expression. This increase was caused by an up-regulation of visfatin in hepatocytes and Kupffer cells as determined by immunohistochemistry.

Conclusions: Taken together, our data demonstrate that visfatin is upregulated in human as well as in experimental liver disease. The observed results would suggest a potential role of this novel adipocytokine in the pathogenesis of chronic liver disease which warrants further examination.