Lipoic Acid Prevents the Changes of Intracellular Lipid Partitioning by Free Fatty Acid

BACKGROUND/AIMS It is suggested that the hepatic lipid composition is more important than lipid quantity in the pathogenesis of non-alcoholic steatohepatitis. We examined whether lipoic acid (LA) could alter intrahepatic lipid composition and free cholesterol distribution. METHODS HepG2 cells were cultured with palmitic acid (PA) with and without LA. Apoptosis, changes of the mitochondrial structure, intracellular lipid partitioning, and reactive oxygen species (ROS) activity were measured. RESULTS Free fatty acid (FA) increased apoptosis, and LA co-treatment prevented this lipotoxicity (apoptosis in controls vs PA vs PA+LA, 0.5% vs 19.5% vs 1.6%, p<0.05). LA also restored the intracellular mitochondrial DNA copy number (553±33.8 copies vs 291±14.55 copies vs 421±21.05 copies, p<0.05) and reversed the morphological changes induced by PA. In addition, ROS was increased in response to PA and was decreased in response to LA co-treatment (41,382 relative fluorescence unit [RFU] vs 43,646 RFU vs 41,935 RFU, p<0.05). LA co-treatment increased the monounsaturated and polyunsaturated FA concentrations and decreased the total saturated FA fraction. It also prevented the movement of intracellular free cholesterol from the cell membrane to the cytoplasm. CONCLUSIONS LA opposes free FA-generated lipotoxicity by altering the intracellular lipid composition and free cholesterol distribution.