Saturated free fatty acid, palmitic acid, induces apoptosis in fetal hepatocytes in culture.

To investigate the effects of saturated free fatty acid, palmitic acid (PA), on hepatocytes, we administered PA to rat hepatocytes. We demonstrated that PA inhibited the cell growth as a dose- and time-dependent manner in rat hepatocytes. PA-induced morphological changes including swelling, membrane dissolution and formation of debris, and apoptosis with appearance of sub-G1 fraction determined by cell cycle analysis after treatment for 4 days. The level of Bcl-2 was slightly decreased, in contrast, the level of Bax elevated markedly, which resulted in a significant decrease of Bcl-2/Bax ratio after PA treatment on HepG2 cells. These findings demonstrated that PA induces cell death on hepatocytes, perhaps via mitochondria-mediated apoptosis. Furthermore, the present study indicates that PA's cell toxicity may play important roles in the transition from steatosis to steatohepatitis in human especially with obesity.