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

Project team:

Ancha Baranova, Karen Schlauch, Hazem Elariny , Mohammed Jarrar, Chase Bennett , Clare Nugent , Shobha J. Gowder, Rochelle Collantes, Vikas Chandhoke, Zobair M. Younossi

This is a collaborative project with Center for Liver Diseases, INOVA Hospital.

Background/Aims: NAFLD and its progressive form, non-alcoholic steatohepatitis (NASH), are among the least understood metabolic consequences of obesity. The role of omental adipose tissue, as a biologically active organ, in the pathogenesis of NAFLD has been increasingly recognized. Differences in transcriptional regulation of these two organs may give important clues into the pathogenesis of NAFLD and its progression.

Methods: Liver and visceral adipose specimens of morbidly obese patients undergoing bariatric surgery were transcriptionally profiled. Functional analyses with the Ingenuity Pathways Knowledge Base (IPKB) and IPA 4.0 software identified genes playing potentially hepatoprotective roles as well as those potentially involved in the pathogenesis of NASH. TNFalpha and IL6 were measured in the serum samples.

Results : A prominent adipose-specific deregulation of the inflammation and immune system related genes were revealed in NASH. A number of liver and adipose-specific functional networks, including these centered at TNFalpha, JUN/JUNB and IFNgamma were highlighted as related to the NASH pathogenesis. There are compensatory increases in the hepatic detoxification enzymes and decreases in the gene network controlled by transcription factor COUP-TFII.

Conclusion: Our findings support the hypothesis of the importance of adipocyte secretion in the development of non-alcoholic fatty liver disease.

List of Supplementary Tables

Supplementary Table 1. A comparison of adipose of obese NASH patients (N=10) vs. adipose of non-Obese Controls (N=9)

Supplementary Table 2. A comparison of adipose of Obese Controls (N=17) vs. adipose of non-Obese Controls (N=9)

Supplementary Table 3. A comparison of liver biopsies of obese patients with NASH (N=27) vs. liver biopsies of non-Obese Controls (N=6)

Supplementary Table 4. A comparison of liver biopsies of Obese Controls N=7) vs. liver biopsies of non-Obese Controls (N=6)

Supplementary Table 5. A total of 97 genes expressed in human adipose tissue were independently identified as statistically significant in the comparisons of obese NASH patients (N=10) vs. non-Obese Controls (N=9), and comparisons of Obese Controls (N=17) vs. non-Obese Controls (N=9)

Supplementary Table 6. A total of 14 genes expressed in hepatic tissue were independently identified as statistically significant in the comparisons of obese NASH patients (N=27) vs. non-Obese Controls (N=6), and obese (N=7) vs. non-Obese Controls (N=6)

Supplementary Table 7. Potential NASH-related genes expressed in adipose tissue

Supplementary Table 8. Potentially hepatoprotective genes expressed in adipose.

Supplementary Table 9. Potentially NASH related genes expressed in the liver.

Supplementary Table 10. Potentially hepatoprotective genes expressed in the liver.