AMPK activation increases fatty acid oxidation in skeletal muscle by activating PPARalpha and PGC-1

Biochem Biophys Res Commun. 2006 Feb 3;340(1):291-5. doi: 10.1016/j.bbrc.2005.12.011. Epub 2005 Dec 12.

Abstract

AMP-activated protein kinase (AMPK) activation increases fatty acid oxidation in skeletal muscle by decreasing malonyl CoA concentrations. However, this may not explain the long-term effects of AMPK activation. Here we show that AMPK activation by 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) increases mRNA expression of PPARalpha target genes and PGC-1 in cultured muscle cells and mouse skeletal muscle, and that inhibition of PPARalpha and PGC-1 by siRNAs prevents AICAR-stimulated increase in fatty acid oxidation. These data suggest that a novel transcriptional regulatory mechanism involving PPARalpha and PGC-1 exists that is responsible for long-term stimulation of fatty acid oxidation in skeletal muscle by AICAR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases
  • Aminoimidazole Carboxamide / analogs & derivatives
  • Aminoimidazole Carboxamide / pharmacology
  • Animals
  • Cells, Cultured
  • Enzyme Activation / drug effects
  • Fatty Acids / metabolism*
  • Lipid Peroxidation / drug effects
  • Lipid Peroxidation / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Multienzyme Complexes / metabolism*
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism*
  • Myoblasts, Skeletal / drug effects
  • Myoblasts, Skeletal / metabolism*
  • Oxidation-Reduction
  • PPAR alpha / deficiency
  • PPAR alpha / metabolism*
  • Protein-Serine-Threonine Kinases / metabolism*
  • Ribonucleotides / pharmacology
  • Transcription Factors / deficiency
  • Transcription Factors / metabolism*
  • Transcriptional Activation / drug effects
  • Transcriptional Activation / physiology

Substances

  • Fatty Acids
  • Multienzyme Complexes
  • PPAR alpha
  • Ribonucleotides
  • Transcription Factors
  • peroxisome-proliferator-activated receptor-gamma coactivator-1
  • Aminoimidazole Carboxamide
  • Protein-Serine-Threonine Kinases
  • AMP-Activated Protein Kinases
  • AICA ribonucleotide