Expression of cytokine signaling genes in morbidly obese patients with non-alcoholic steatohepatitis and hepatic fibrosis.
BACKGROUND
White adipose tissue (WAT) from visceral adiposity plays an important role in the pathogenesis of non-alcoholic steatohepatitis (NASH). Development of NASH and its progression to fibrosis is partially due to cytokines and adipokines produced by WAT. The aim of this study was to assess the association of hepatic fibrosis and NASH by evaluating the intrinsic differences in the inflammatory cytokine signaling in the visceral adipose tissue obtained from morbidly obese patients.


METHODS
We used targeted microarrays representing human genes involved in the inflammatory and fibrogenic reactions to profile visceral adipose samples of 15 well-matched NASH patients with and without fibrosis. Additionally, visceral adipose samples were subjected to real-time polymerase chain reaction profiling of 84 inflammations related genes.


RESULTS
Eight genes (CCL2, CCL4, CCL18, CCR1, IL10RB, IL15RA, and LTB) were differentially expressed in NASH with fibrosis. Additionally, an overlapping but distinct list of the differentially expressed genes were found in NASH with type II diabetes (DM; IL8, BLR1, IL2RA, CD40LG, IL1RN, IL15RA, and CCL4) as compared to NASH without DM.


CONCLUSIONS
Inflammatory cytokines are differentially expressed in the adipose tissue of NASH with fibrosis, as well in NASH with DM. These findings point at the interaction of adipose inflammatory cytokines, DM, hepatic fibrosis in NASH, and its progression to cirrhosis and end-stage liver disease.
Estep
J Michael
JM
Center for Liver Diseases, Inova Fairfax Hospital, 3300 Gallows Road, Falls Church, VA, 22042, USA.
Baranova
Ancha
A
Hossain
Noreen
N
Elariny
Hazem
H
Ankrah
Kathy
K
Afendy
Arian
A
Chandhoke
Vikas
V
Younossi
Zobair M
ZM
D000328:Adult; D016022:Case-Control Studies; D016207:Cytokines / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics / Q000473:pathology; D005234:Fatty Liver / Q000150:complications / Q000235:genetics* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D050152:Intra-Abdominal Fat; D008103:Liver Cirrhosis / Q000150:complications / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009767:Obesity, Morbid / Q000150:complications* / Q000235:genetics* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D018121:Receptors, Cytokine / Q000235:genetics*
D016207:Cytokines; D018121:Receptors, Cytokine