Gene expression patterns in hepatic tissue and visceral adipose tissue of patients with non-alcoholic fatty liver disease.
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.


CONCLUSIONS
Our findings support the hypothesis that adipocyte secretion plays an important role in the development of NAFLD.
Baranova
Ancha
A
Center for Liver Diseases, Inova Fairfax Hospital, Fairfax, VA 22042, USA.
Schlauch
Karen
K
Elariny
Hazem
H
Jarrar
Mohammed
M
Bennett
Chase
C
Nugent
Clare
C
Gowder
Shobha J
SJ
Younoszai
Zahra
Z
Collantes
Rochelle
R
Chandhoke
Vikas
V
Younossi
Zobair M
ZM
D017667:Adipocytes / Q000502:physiology*; D000328:Adult; D004797:Enzyme-Linked Immunosorbent Assay; D005234:Fatty Liver / Q000235:genetics* / Q000503:physiopathology / Q000517:prevention & control; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology*; D016758:Genes, jun / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000502:physiology; D015850:Interleukin-6 / Q000097:blood; D050152:Intra-Abdominal Fat / Q000166:cytology* / Q000378:metabolism; D020738:Leptin / Q000378:metabolism; D008099:Liver / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics / Q000378:metabolism; D040081:Protein Array Analysis; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D015850:Interleukin-6; D020738:Leptin; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma