Peroxisome proliferator-activated receptor alpha-responsive genes induced in the newborn but not prenatal liver of peroxisomal fatty acyl-CoA oxidase null mice.

Mice deficient in fatty acyl-CoA oxidase (AOX(-/-)), the first enzyme of the peroxisomal beta-oxidation system, develop specific morphological and molecular changes in the liver characterized by microvesicular fatty change, increased mitosis, spontaneous peroxisome proliferation, increased mRNA and protein levels of genes regulated by peroxisome proliferator-activated receptor alpha (PPARalpha), and hepatocellular carcinoma. Based on these findings it is proposed that substrates for AOX function as ligands for PPARalpha. In this study we examined the sequential changes in morphology and gene expression in the liver of wild-type and AOX(-/-) mice at Embryonic Day 17.5, and during postnatal development up to 2 months of age. In AOX(-/-) mice high levels of expression of PPARalpha-responsive genes in the liver commenced on the day of birth and persisted throughout the postnatal period. We found no indication of PPARalpha activation in the livers of AOX(-/-) mice at embryonic age E17.5. In AOX(-/-) mice microvesicular fatty change in liver cells was evident at 7 days. At 2 months of age livers showed extensive steatosis and the presence in the periportal areas of clusters of hepatocytes with abundant granular eosinophilic cytoplasm rich in peroxisomes. These results suggest that the biological ligands for PPARalpha vis a vis substrates for AOX either are not functional in fetal liver or do not cross the placental barrier during the fetal development and that postnatally they are likely derived from milk and diet.

Cook WS ，Jain S ，Jia Y ，Cao WQ ，Yeldandi AV ，Reddy JK ，Rao MS ... -  《EXPERIMENTAL CELL RESEARCH》

Expression of peroxisome proliferator-activated receptor alpha, and PPARalpha regulated genes in spontaneously developed hepatocellular carcinomas in fatty acyl-CoA oxidase null mice.

Meyer K ，Jia Y ，Cao WQ ，Kashireddy P ，Rao MS ... -  《INTERNATIONAL JOURNAL OF ONCOLOGY》

Absence of spontaneous peroxisome proliferation in enoyl-CoA Hydratase/L-3-hydroxyacyl-CoA dehydrogenase-deficient mouse liver. Further support for the role of fatty acyl CoA oxidase in PPARalpha ligand metabolism.

Qi C ，Zhu Y ，Pan J ，Usuda N ，Maeda N ，Yeldandi AV ，Rao MS ，Hashimoto T ，Reddy JK ... -  《JOURNAL OF BIOLOGICAL CHEMISTRY》

Differential induction of genes in liver and brown adipose tissue regulated by peroxisome proliferator-activated receptor-alpha during fasting and cold exposure in acyl-CoA dehydrogenase-deficient mice.

Goetzman ES ，Tian L ，Wood PA 《MOLECULAR GENETICS AND METABOLISM》

Comparison of constitutive and inducible levels of expression of peroxisomal beta-oxidation and catalase genes in liver and extrahepatic tissues of rat.

Nemali MR ，Usuda N ，Reddy MK ，Oyasu K ，Hashimoto T ，Osumi T ，Rao MS ，Reddy JK ... -  《CANCER RESEARCH》