Abstract:
The role of obesity in the development of non-alcoholic fatty liver disease (NAFLD), and
its more severe manifestation non-alcoholic steatohepatitis (NASH), is due, in part, to
changes in the milieu of the cytokines and adipokines produced by the adipose tissue. A
significant portion of patients with NAFLD subsequently develop other liver pathology,
including hepatic fibrosis. The development of the hepatic fibrosis in some, but not all,
NASH patients may reside in intrinsic differences in the spectrum or volume of the
cytokine production by the visceral adipose. To test this hypothesis, targeted microarrays
representing human genes involved in the inflammatory and fibrotic reactions were
employed to profile visceral adipose samples of well-matched cohorts of NASH patients
with and without concomitant fibrosis. Additionally, visceral adipose samples were
subjected to Real-Time PCR profiling of 84 inflammation related genes. Several genes,
including CCL2 and IL15R, were found to be differentially expressed in NASH patients
with fibrosis, while other genes, such as that for CD40 ligand, showed a relationship to
both fibrosis and diabetes. These differences may help to understand molecular
underpinnings of NASH progression.
