Altered Constitutive Expression of Fatty Acid-metabolizing Enzymes in Mice Lacking the Peroxisome Proliferator-activated Receptor a (PPARa)*

Peroxisome proliferator-activated receptor a (PPARa) is a member of the steroid/nuclear receptor superfamily and mediates the biological and toxicological effects of peroxi-some proliferators. To determine the physiological role of PPARa in fatty acid metabolism, levels of peroxisomal and mitochondrial fatty acid metabolizing enzymes were deter-mined in the PPARa null mouse. Constitutive liver b-oxida-tion of the long chain fatty acid, palmitic acid, was lower in the PPARa null mice as compared with wild type mice, indicating defective mitochondrial fatty acid catabolism. In contrast, constitutive oxidation of the very long chain fatty acid, lignoceric acid, was not different between wild type and PPARa null mice, suggesting that constitutive expres-sion of enzymes involved in peroxisomal b-oxidation is in-dependent of PPARa. Indeed, the PPARa null mice ha