Enhancement of peroxisomal beta-oxidation in the liver of rats and mice treated with valproic acid.

The effects of valproic acid on peroxisomal beta-oxidation and on lipid levels of liver and serum in the rat and mouse were studied. When the animals were fed diet containing 1% valproic acid for 2 weeks, the activity of peroxisomal beta-oxidation increased 4-fold in the rat liver and 2-fold in the mouse liver. Other peroxisomal enzymes such as catalase and urate oxidase also increased by the treatment though to a lesser extent than beta-oxidation. The contents of triglyceride and cholesterol in the serum decreased significantly in the rat but not in the mouse. The time course curves of the activities of cyanide-insensitive palmitoyl-CoA oxidation and carnitine-dependent palmitoyltransferase indicated that peroxisomal beta-oxidation was enhanced more rapidly than that of mitochondrial. The distributions of these enzymes were not changed by the treatment with valproic acid, though increases in liver weight and protein content were observed. These results indicate that the action of valproic acid in enhancing hepatic beta-oxidation is similar to that of clofibrate and other hypolipidemic drugs.