Reduced hepatic fatty acid oxidation in fasting PPARalpha null mice is due to impaired mitochondrial hydroxymethylglutaryl-CoA synthase gene expression

FEBS Lett. 2000 Jun 23;475(3):163-6. doi: 10.1016/s0014-5793(00)01648-3.


Glucose and fatty acid metabolism (oxidation versus esterification) has been measured in hepatocytes isolated from 24 h starved peroxisome proliferator-activated receptor-alpha (PPARalpha) null and wild-type mice. In PPARalpha null mice, the development of hypoglycemia during starvation was due to a reduced capacity for hepatic gluconeogenesis secondary to a 70% lower rate of fatty acid oxidation. This was not due to inappropriate expression of the hepatic CPT I gene, which was similar in both genotypes, but to impaired mitochondrial hydroxymethylglutaryl-CoA synthase gene expression in the PPARalpha null mouse liver. We also demonstrate that hepatic steatosis of fasting PPARalpha null mice was not due to enhanced triglyceride synthesis.

MeSH terms

  • Animals
  • Gene Expression Regulation, Enzymologic
  • Hydroxymethylglutaryl-CoA Synthase / genetics
  • Hydroxymethylglutaryl-CoA Synthase / metabolism*
  • Liver / metabolism*
  • Mice
  • Mice, Knockout
  • Mitochondria, Liver / genetics
  • Mitochondria, Liver / metabolism
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Oxidation-Reduction
  • Receptors, Cytoplasmic and Nuclear / genetics*
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism*


  • Nuclear Proteins
  • Receptors, Cytoplasmic and Nuclear
  • Transcription Factors
  • Hydroxymethylglutaryl-CoA Synthase