Gene Expression Patterns in Hepatic Tissue and Visceral Adipose Tissue of Patients with Non-Alcoholic Fatty Liver Disease

Abstract

Non-alcoholic fatty liver disease (NAFLD) and its progressive form, non-alcoholic steatohepatitis (NASH), are among the least understood metabolic consequences of obesity. Increasingly, omental adipose tissue is recognized as a biologically active organ in the pathogenesis of NAFLD. Differences in transcriptional regulation in omental adipose tissue and liver tissue may provide important insights into the pathogenesis of NAFLD and its progression. Transcriptional profiles were obtained for liver and visceral adipose specimens of morbidly obese patients undergoing bariatric surgery. Functional analyses with the Ingenuity Pathways Knowledge Base (IPKB) and IPA 4.0 software identified genes that potentially play hepatoprotective roles as well as those potentially involved in the pathogenesis of NASH. TNFalpha and IL6 were measured in the serum samples. Tissue from patients with NASH showed prominent adipose-specific deregulation of genes related to inflammation and the immune system. A number of liver and adipose-specific functional networks, including those centered at TNFalpha, JUN/JUNB, and IFNgamma were highlighted as related to the NASH pathogenesis. The results also showed compensatory increases in hepatic detoxification enzymes and decreases in the gene network controlled by transcription factor COUP-TFII. Our findings support the hypothesis that adipocyte secretion plays an important role in the development of NAFLD.