title: AMPK activation increases fatty acid oxidation in skeletal muscle by activating PPARalpha and PGC-1.
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.
authors.affiliation: Department of Internal Medicine, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Woo Je
authors.initials: WJ
authors.lastname: Lee
authors.forename: Mina
authors.initials: M
authors.lastname: Kim
authors.forename: Hye-Sun
authors.initials: HS
authors.lastname: Park
authors.forename: Hyoun Sik
authors.initials: HS
authors.lastname: Kim
authors.forename: Min Jae
authors.initials: MJ
authors.lastname: Jeon
authors.forename: Ki Sook
authors.initials: KS
authors.lastname: Oh
authors.forename: Eun Hee
authors.initials: EH
authors.lastname: Koh
authors.forename: Jong Chul
authors.initials: JC
authors.lastname: Won
authors.forename: Min-Seon
authors.initials: MS
authors.lastname: Kim
authors.forename: Goo Taeg
authors.initials: GT
authors.lastname: Oh
authors.forename: Michung
authors.initials: M
authors.lastname: Yoon
authors.forename: Ki-Up
authors.initials: KU
authors.lastname: Lee
authors.forename: Joong-Yeol
authors.initials: JY
authors.lastname: Park
mesh_terms: 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
chemical_list: 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