['Mitochondrial dysfunction and hepatocyte cell death have been reported in fatty liver and non-alcoholic steatohepatitis. Our aim in this study was to evaluate whether direct exposure of hepatocytes to extracellular fat could facilitate such deleterious effects.', 'FaO hepatic cells treated with fat was used as an in vitro model for steatosis. FaO hepatocytes were exposed to 0.1% triacylglycerols using commercially available lipid emulsion (LE) for various periods and studied for production of reactive oxygen species (ROS), mitochondrial function, and cell death parameters. To study the type of cell death, high-mobility group box chromosomal protein 1cellular levels, DNA fragmentation, and caspase activity were evaluated.', 'Cells incubated with LE for 6 h exhibited a marked increase in the production of intracellular ROS. Using treatments with peroxisome proliferator-activated receptor activators, mitochondrial electron-transfer chain inhibitor, and different sources of LE that did or did not contain medium-chain triacylglycerols, the mitochondria were found to be the source of ROS. LE treatment resulted in phosphorylation of adenosine monophosphate-activated protein kinase, accompanied by a decrease in adenosine triphosphate levels. Changes in intracellular ROS and energy levels were followed by cell death. FaO hepatocytes showed a significant reduction in high-mobility group box chromosomal protein-1 and little DNA fragmentation. Incubation with LE for 24 h did not change caspase-3 activity, indicating that hepatocyte death was necrotic. The antioxidant N-acetylcysteine was able to attenuate the changes in intracellular energy levels and ROS levels and to prevent cell death after exposure to LE.'] Does nutritional lipid-induced oxidative stress lead to mitochondrial dysfunction followed by necrotic death in FaO hepatocytes?