::  A N C H A   L A B  ::
:: WELCOME
:: FOCUS OF THE LAB
:: METHODS
:: PAPERS
:: COURSES
:: JOURNAL CLUB
:: PEOPLE
:: AWARDS
:: CONTACT ME
:: LAB ALUMNI
 
Gene expression patterns in hepatic tissue and visceral adipose tissue of patients with non-alcoholic fatty liver disease.
Ancha Baranova, Karen Schlauch, Hazem Elariny, Mohammed Jarrar, Chase Bennett, Claire Nugent, Shobha Gowder, Zahra Younoszai, Rochelle Collantes, 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. 2007 Aug;17(8):1111-8.

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.

Figure 1. A. TNFα and IL6 regulated genes expressed in adipose play a prominent role in the development of NASH (For the complete list of genes and their functions, see Supplementary Table 7). B. Genes that are regulated by TGF-β signal in adipose are important for the development of the primary phenotype of morbid obesity (For the complete list of genes and their functions, see Supplementary Table 5).

Figure 2. IFN-γ (A), JUN/JUNB (B), and Leptin/TNFα (C) regulated genes protect the livers of a subgroup of morbidly obese patients against the development of steatosis (For the complete list of genes and their functions, see Supplementary Table 10).

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.