Summary. Non-alcoholic fatty liver disease (NAFLD)
encompasses the whole spectrum of steatosis, nonalcoholic
steatohepatitis (NASH), and NASH-related
cirrhosis (NASH/Cir). Although molecular advances
have been made in this field, the pathogenesis of
NAFLD is not completely understood. The gene
expression profiling associated to NASH/Cir was
assessed, in an attempt to better characterize the
pathways involved in its etiopathogenesis. Methods: In
the first step, we used cDNA microarray to evaluate the
gene expression profiles in normal liver (n=3) and
NASH/Cir samples (n=3) by GeneSifter™ analysis to
identify differentially expressed genes and biological
pathways. Second, tissue microarray was used to
determine immunohistochemical expression of
phosphorylated mTOR and 4E-BP1 in 11 normal liver
samples, 10 NASH/Cir samples and in 37 samples of
cirrhosis of other etiologies to further explore the
involvement of the mTOR pathway evidenced by the
gene expression analysis. Results: 138 and 106 genes
were, respectively, up and down regulated in NASH/Cir
in comparison to normal liver. Among the 9 pathways
identified as significantly modulated in NASH/Cir, the
participation of the mTOR pathway was confirmed,
since expression of cytoplasmic and membrane phosphomTOR
were higher in NASH/Cir in comparison to
cirrhosis of other etiologies and to normal liver.
Conclusions: Recent findings have suggested a role for
the cellular “nutrient sensor” mTOR in NAFLD and the
present study corroborates the participation of this
pathway in NASH/Cir. Phospho-mTOR evaluation
might be of clinical utility as a potential marker for
identification of NASH/Cir in cases mistakenly
considered as cryptogenic cirrhosis owing to paucity of
clinical data