BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) and its progressive form,non-alcoholic steatohepatitis (NASH), are among the least understood metabolicconsequences of obesity. Increasingly, omental adipose tissue is recognized as a biologically active organ in the pathogenesis of NAFLD. Differences intranscriptional regulation in omental adipose tissue and liver tissue may provideimportant insights into the pathogenesis of NAFLD and its progression. METHODS:Transcriptional profiles were obtained for liver and visceral adipose specimensof morbidly obese patients undergoing bariatric surgery. Functional analyses withthe Ingenuity Pathways Knowledge Base (IPKB) and IPA 4.0 software identifiedgenes that potentially play hepatoprotective roles as well as those potentiallyinvolved in the pathogenesis of NASH. TNFalpha and IL6 were measured in the serumsamples. RESULTS: Tissue from patients with NASH showed prominentadipose-specific deregulation of genes related to inflammation and the immunesystem. A number of liver and adipose-specific functional networks, includingthose centered at TNFalpha, JUN/JUNB, and IFNgamma were highlighted as related tothe NASH pathogenesis. The results also showed compensatory increases in hepatic detoxification enzymes and decreases in the gene network controlled bytranscription factor COUP-TFII. CONCLUSION: Our findings support the hypothesisthat adipocyte secretion plays an important role in the development of NAFLD.

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