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Obesity-related differential gene expression in the visceral adipose tissue.
Ancha Baranova, Rochelle Collantes, Shobha Gowder, Hazem Elariny, Karen Schlauch, Abraham Younoszai, Steve King, Manpreet Randhawa, Sitapati Pusulury, Tariq Alsheddi, Janus Ong, Lisa Martin, Vikas Chandhoke, Zobair M. Younossi

This is a collaborative project between

Molecular and Microbiology Department, College of Science,George Mason University, Fairfax, VA

Translational Reseach Institute, Inova Hospital, VA

This study was published in: Obes Surg. 2005 Jun-Jul;15(6):758-65.

BACKGROUND: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSION: Our findings support the hypothesis that adipocyte secretion plays an important role in the development of NAFLD.

Supplementary Table 1. Known Human Genes found to be differentiallly expressed in MO vs.CONTROLS comparison

Supplementary Table 2. cDNAs representing ESTs/predicted genes that found to be differentially expressed in MO vs.CONTROLS comparison

Supplementary Table 3. Known human genes found to be differentially expressed in all three comparisons (MO vs CONTROLS, NGO vs CONTROLS, DMO vs.CONTROLS).

Figure 1. Venn diagram depicting pairwise intersections of significantly differentially expressed genes obtained in the three comparisons: morbidly obese (MO) vs controls (dark circle), obese diabetics (DMO) vs controls (grey circle) and normoglycemic obese (NGO) vs controls (pale circle).