Hepatic expression patterns of inflammatory and immune response genes associated with obesity and NASH in morbidly obese patients.
BACKGROUND
Obesity modulates inflammation and activation of immune pathways which can lead to liver complications. We aimed at identifying expression patterns of inflammatory and immune response genes specifically associated with obesity and NASH in the liver of morbidly obese patients.


RESULTS
Expression of 222 genes was evaluated by quantitative RT-PCR in the liver of morbidly obese patients with histologically normal liver (n = 6), or with severe steatosis without (n = 6) or with NASH (n = 6), and in lean controls (n = 5). Hepatic expression of 58 out of 222 inflammatory and immune response genes was upregulated in NASH patients. The most notable changes occurred in genes encoding chemokines and chemokine receptors involved in leukocyte recruitment, CD and cytokines involved in the T cell activation towards a Th1 phenotype, and immune semaphorins. This regulation seems to be specific for the liver since visceral adipose tissue expression and serum levels of MCP1, IP10, TNFα and IL6 were not modified. Importantly, 47 other genes were already upregulated in histologically normal liver (e.g. CRP, Toll-like receptor (TLR) pathway). Interestingly, serum palmitate, known to activate the TLR pathway, was increased with steatosis.


CONCLUSIONS
The liver of obese patients without histological abnormalities already displayed a low-grade inflammation and could be more responsive to activators of the TLR pathway. NASH was then characterized by a specific gene signature. These findings help to identify new potential actors of the pathogenesis of NAFLD.
INSERM U895, Team 8 Hepatic Complications of Obesity, Nice, France.
Adeline
A
Bertola
Stéphanie
S
Bonnafous
Rodolphe
R
Anty
Stéphanie
S
Patouraux
Marie-Christine
MC
Saint-Paul
Antonio
A
Iannelli
Jean
J
Gugenheim
Jonathan
J
Barr
José M
JM
Mato
Yannick
Y
Le Marchand-Brustel
Albert
A
Tran
Philippe
P
Gual
D000328:Adult; D016022:Case-Control Studies; D005234:Fatty Liver / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D008099:Liver / Q000378:metabolism*; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease; D009767:Obesity, Morbid / Q000235:genetics* / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction