Hepatic gene expression in patients with obesity-related non-alcoholic steatohepatitis.
BACKGROUND
Non-alcoholic fatty liver disease (NAFLD) is among the most common causes of chronic liver disease. NAFLD includes a spectrum of clinicopathologic syndromes that includes non-alcoholic steatohepatitis (NASH) that has potential for progression. The pathogenesis of NASH is poorly characterized.


OBJECTIVE
This study was designed to identify differences in hepatic gene expression in patients with NASH and to relate such differences to their clinical characteristics.


METHODS
Consecutive patients undergoing bariatric surgery were prospectively recruited. Extensive clinical data and two liver biopsy specimens were obtained at the time of enrollment. A single hepatopathologist reviewed and classified the liver biopsies. Patients with excessive alcohol use and other causes of liver disease were excluded. A group of 29 NASH patients, 12 with steatosis alone, seven obese controls and six non-obese controls were selected for further investigation. Customized cDNA microarrays containing 5220 relevant genes were designed specifically for this study. Microarray experiments were run in triplicate for each sample and a selected group of genes were confirmed using real-time PCR.


METHODS
Differential hepatic gene expressions in patients with NASH as compared with controls.


RESULTS
Thirty-four genes with significant differential expression were identified in patients with NASH when compared with non-obese controls. Moreover, 19 of these genes showed no significant expression differences in obese vs. non-obese controls, suggesting a stronger association of these genes to NASH.


CONCLUSIONS
Several differentially expressed genes in patients with NASH are related to lipid metabolism and extracellular matrix remodeling. Additionally, genes related to liver regeneration, apoptosis, and the detoxification process were differentially expressed. These findings may help clarify the molecular pathogenesis of NASH and identify potential targets for therapeutic intervention.
Younossi
Zobair M
ZM
Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, VA, USA.
Gorreta
Francesco
F
Ong
Janus P
JP
Schlauch
Karen
K
Del Giacco
Luca
L
Elariny
Hazem
H
Van Meter
Amy
A
Younoszai
Abraham
A
Goodman
Zachary
Z
Baranova
Anna
A
Christensen
Alan
A
Grant
Geraldine
G
Chandhoke
Vikas
V
D000328:Adult; D005234:Fatty Liver / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology*; D006505:Hepatitis / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D011446:Prospective Studies; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014768:Virginia / Q000453:epidemiology
D011506:Proteins; D012333:RNA, Messenger