Effect of intracellular lipid accumulation in a new model of non-alcoholic fatty liver disease Full Text
BMC Gastroenterology, 03/02/2012
Chavez–Tapia NC et al. – 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 free fatty acids (FFA) in the pathogenesis of Non–Alcoholic Fatty Liver Disease (NAFLD) and Non–Alcoholic Steatohepatitis (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.
- 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.