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Logo of bmcgastBioMed Centralsearchsubmit a manuscriptregisterthis articleBMC Gastroenterology
 
BMC Gastroenterol. 2012; 12: 20.
Published online Mar 1, 2012. doi:  10.1186/1471-230X-12-20
PMCID: PMC3313845
Effect of intracellular lipid accumulation in a new model of non-alcoholic fatty liver disease
Norberto C Chavez-Tapia,corresponding author1,2,3 Natalia Rosso,1 and Claudio Tiribelli1
1Fondazione Italiana Fegato- Centro Studi Fegato, AREA SCIENCE Park Basovizza, Bldg Q, Trieste, Italy
2Centro Studi Fegato, AREA Science Park, Bldg.Q. SS 14 km 163.5. 34012, Trieste, Italy
3Medica Sur Clinic and Foundation, Mexico City, Mexico
corresponding authorCorresponding author.
Norberto C Chavez-Tapia: khavez/at/gmail.com; Natalia Rosso: natalia.rosso/at/csf.units.it; Claudio Tiribelli: ctliver/at/csf.units.it
Received September 14, 2011; Accepted March 1, 2012.
Abstract
Background
In vitro exposure of liver cells to high concentrations of free fatty acids (FFA) results in fat overload which promotes inflammatory and fibrogenic response similar to those observed in patients with Non-Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH). Since the mechanisms of this event have not been fully characterized, we aimed to analyze the fibrogenic stimuli in a new in vitro model of NASH.
Methods
HuH7 cells were cultured for 24 h in an enriched medium containing bovine serum albumin and increasing concentrations of palmitic and oleic acid at a molar ratio of 1:2 (palmitic and oleic acid, respectively). Cytotoxic effect, apoptosis, oxidative stress, and production of inflammatory and fibrogenic cytokines were measured.
Results
FFA induces a significant increment in the intracellular content of lipid droplets. The gene expression of interleukin-6, interleukin-8 and tumor necrosis factor alpha was significantly increased. The protein level of interleukin-8 was also increased. Intracellular lipid accumulation was associated to a significant up-regulation in the gene expression of transforming growth factor beta 1, alpha 2 macroglobulin, vascular endothelial growth factor A, connective tissue growth factor, insulin-like growth factor 2, thrombospondin 1. Flow cytometry analysis demonstrated a significant increment of early apoptosis and production of reactive oxygen species.
Conclusions
The exposure of hepatocytes to fatty acids elicits inflammation, increase of oxidative stress, apoptosis and production of fibrogenic cytokines. These data support a primary role of FFA in the pathogenesis of NAFLD and NASH.
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