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
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Research Support, Non-U.S. Gov't
MeSH terms
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AMP-Activated Protein Kinases
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Aminoimidazole Carboxamide / analogs & derivatives
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Aminoimidazole Carboxamide / pharmacology
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Animals
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Cells, Cultured
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Enzyme Activation / drug effects
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Fatty Acids / metabolism*
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Lipid Peroxidation / drug effects
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Lipid Peroxidation / physiology*
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Multienzyme Complexes / metabolism*
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Muscle, Skeletal / drug effects
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Muscle, Skeletal / metabolism*
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Myoblasts, Skeletal / drug effects
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Myoblasts, Skeletal / metabolism*
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Oxidation-Reduction
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PPAR alpha / deficiency
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PPAR alpha / metabolism*
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Protein Serine-Threonine Kinases / metabolism*
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Ribonucleotides / pharmacology
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Transcription Factors / deficiency
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Transcription Factors / metabolism*
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Transcriptional Activation / drug effects
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Transcriptional Activation / physiology
Substances
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Fatty Acids
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Multienzyme Complexes
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PPAR alpha
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Ribonucleotides
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Transcription Factors
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peroxisome-proliferator-activated receptor-gamma coactivator-1
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Aminoimidazole Carboxamide
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Protein Serine-Threonine Kinases
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AMP-Activated Protein Kinases
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AICA ribonucleotide