Overexpression of UCP-3 in skeletal muscle of mice results in increased expression of mitochondrial thioesterase mRNA

Biochem Biophys Res Commun. 2001 May 18;283(4):785-90. doi: 10.1006/bbrc.2001.4848.

Abstract

Mice overexpressing human UCP-3 in skeletal muscle (UCP-3tg) are lean despite overeating, have increased metabolic rate, and their skeletal muscle mitochondria show increased proton conductance. The true function of UCP-3 however, has yet to be determined. It is assumed that UCP-3tg mice have increased fatty acid beta-oxidation to fuel their increased metabolic rate. In this study we have quantified skeletal muscle mRNA levels of a number of genes involved in fatty acid metabolism. mRNA levels of uncoupling protein-2, carnitine palmitoyl transferase-1beta and fatty acid binding proteins, and transporters were unchanged when compared to wild-type mice. Lipoprotein lipase mRNA was slightly, but significantly, increased by 50%. The most notable change in gene expression was a threefold increase in mitochondrial thioesterase (MTE-1) expression. In the face of a chronic increase in mitochondrial uncoupling these changes suggest that increased flux of fatty acids through the beta-oxidation pathway does not necessarily require marked changes in expression of genes involved in fatty acid metabolism. The large increase in MTE-1 both confirms the importance of this gene in situations where mitochondrial beta-oxidation is increased and supports the hypothesis that UCP-3 exports fatty acids generated by MTE-1 in the mitochondrion.

MeSH terms

  • Animals
  • Base Sequence
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism
  • DNA
  • Ion Channels
  • Male
  • Mice
  • Mitochondria / enzymology*
  • Mitochondrial Proteins
  • Molecular Sequence Data
  • Muscle, Skeletal / metabolism*
  • Palmitoyl-CoA Hydrolase / genetics*
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Uncoupling Protein 3

Substances

  • Carrier Proteins
  • Ion Channels
  • Mitochondrial Proteins
  • RNA, Messenger
  • UCP3 protein, human
  • Ucp3 protein, mouse
  • Uncoupling Protein 3
  • DNA
  • Palmitoyl-CoA Hydrolase