Less extrahepatic induction of fatty acid β-oxidation enzymes by PPARα

The peroxisome proliferator-activated receptor α (PPARα) is a nuclear receptor that transcriptionally regulates mitochondrial and peroxisomal fatty acid β-oxidation enzymes in the liver. Ligands include synthetic peroxisome proliferators and some fatty acids. PPARα activation leads to predictable pleiotropic responses in liver including peroxisome proliferation, increased fatty acid oxidation, and hepatocellular carcinoma. In the current study, the response to PPARα-activation was compared in the heart, kidney, and liver since the role of PPARα in extrahepatic fatty acid-oxidizing organs has not been fully explored. Basal expression of mitochondrial β-oxidation enzymes was comparable in the three tissues, but peroxisomal β-oxidation enzymes were most abundant in the liver and less so in the kidney and especially in the heart. After PPARα activation with ciprofibrate, both mitochondrial and peroxisomal β-oxidation enzymes were induced, with the strongest response seen in the liver, a moderate response in the kidney, and no significant response in the heart. PPARα mRNA analysis suggested that the differential response may be related to PPARα expression. (C) 2000 Academic Press.