A Role of Excessive Visceral Adipose in the Liver Fibrosis in and NASH progression

Project leader: Mike Estep

This is a collaborative project with Dr. Z.M. Younossi (Center for Liver Diseases, INOVA Hospital)

Nonalcoholic fatty liver disease (NAFLD) especially nonalcoholic steatohepatitis (NASH) is in increased frequency and more common in people with diabetes mellitus and obesity. The outcome of NAFLD is difficult to predict; some patients progress to NASH, some not. Even though, the mysterious pathological reasons behind NASH are not clear, the oxidative stress, the insulin resistance and an imbalance of adipokine production has been considered as major players in NASH pathogenesis.

The important questions related to the pathophysiology of NASH is its influence on the onset and progression of liver fibrosis, which is the end result of several chronic liver diseases. Fibrosis causes various architectural changes in the hepatic parenchyma that lead to progressive reduction of liver function, playing a highly important role in the natural history of NAFLD and NASH. Noninvasive tools are thus needed for measuring hepatic fibrosis in clinical settings and for identifying those NAFLD patients with higher rates of progression. Profiling of cytokines in serum and levels of their gene expression in adipose may provide basis for the development of such non-invasive tool.

This study is aimed at the profiling of the gene expression in the adipose samples of NASH patients with and without firbrosis by mean of microarrays. We chose Superarray Biosciences platform (www. superarray .com/) allowing profiling of approximately 400 genes encoding pro- and anti-inflammatory cytokines as well as their receptors and signaling molecules. Profiling of 25 NASH samples with and without fibrosis will be completed in Summer 2007. The results of this study will be confirmed by Real-Time PCR.