AMPK activation increases fatty acid oxidation in skeletal muscle by activating PPARalpha and PGC-1.
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.
Lee
Woo Je
WJ
Department of Internal Medicine, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Kim
Mina
M
Park
Hye-Sun
HS
Kim
Hyoun Sik
HS
Jeon
Min Jae
MJ
Oh
Ki Sook
KS
Koh
Eun Hee
EH
Won
Jong Chul
JC
Kim
Min-Seon
MS
Oh
Goo Taeg
GT
Yoon
Michung
M
Lee
Ki-Up
KU
Park
Joong-Yeol
JY
D055372:AMP-Activated Protein Kinases; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D005227:Fatty Acids / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009097:Multienzyme Complexes / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D032448:Myoblasts, Skeletal / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D047493:PPAR alpha / Q000172:deficiency / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012265:Ribonucleotides / Q000494:pharmacology; D014157:Transcription Factors / Q000172:deficiency / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects / Q000502:physiology
D005227:Fatty Acids; D009097:Multienzyme Complexes; D047493:PPAR alpha; D012265:Ribonucleotides; D014157:Transcription Factors; C111264:peroxisome-proliferator-activated receptor-gamma coactivator-1; D000620:Aminoimidazole Carboxamide; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide