Visceral Adipose as a Source of Inflammatory Cytokines in NASH, Fibrosis, and Type II Diabetes

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.