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

William S. Cook, Sanjay Jain, Yuzhi Jia, Wen Qing Cao, Anjana V. Yeldandi, Janardan K. Reddy, M. Sambasiva Rao

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Mice deficient in fatty acyl-CoA oxidase (AOX−/−), the first enzyme of the peroxisomal β-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 α (PPARα), and hepatocellular carcinoma. Based on these findings it is proposed that substrates for AOX function as ligands for PPARα. 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 PPARα-responsive genes in the liver commenced on the day of birth and persisted throughout the postnatal period. We found no indication of PPARα 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 PPARα 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.

Original languageEnglish (US)
Pages (from-to)70-76
Number of pages7
JournalExperimental Cell Research
Volume268
Issue number1
DOIs
StatePublished - Aug 1 2001

Keywords

  • Acyl-coa oxidase-deficient mice
  • Developmental regulation
  • Peroxisomes
  • Pparα
  • β-oxidation

ASJC Scopus subject areas

  • Cell Biology

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