title: Glycogen content regulates peroxisome proliferator activated receptor-∂ (PPAR-∂) activity in rat skeletal muscle.
abstract: Performing exercise in a glycogen depleted state increases skeletal muscle lipid utilization and the transcription of genes regulating mitochondrial β-oxidation. Potential candidates for glycogen-mediated metabolic adaptation are the peroxisome proliferator activated receptor (PPAR) coactivator-1α (PGC-1α) and the transcription factor/nuclear receptor PPAR-∂. It was therefore the aim of the present study to examine whether acute exercise with or without glycogen manipulation affects PGC-1α and PPAR-∂ function in rodent skeletal muscle. Twenty female Wistar rats were randomly assigned to 5 experimental groups (n = 4): control [CON]; normal glycogen control [NG-C]; normal glycogen exercise [NG-E]; low glycogen control [LG-C]; and low glycogen exercise [LG-E]). Gastrocnemius (GTN) muscles were collected immediately following exercise and analyzed for glycogen content, PPAR-∂ activity via chromatin immunoprecipitation (ChIP) assays, AMPK α1/α2 kinase activity, and the localization of AMPK and PGC-1α. Exercise reduced muscle glycogen by 47 and 75% relative to CON in the NG-E and LG-E groups, respectively. Exercise that started with low glycogen (LG-E) finished with higher AMPK-α2 activity (147%, p<0.05), nuclear AMPK-α2 and PGC-1α, but no difference in AMPK-α1 activity compared to CON. In addition, PPAR-∂ binding to the CPT1 promoter was significantly increased only in the LG-E group. Finally, cell reporter studies in contracting C2C12 myotubes indicated that PPAR-∂ activity following contraction is sensitive to glucose availability, providing mechanistic insight into the association between PPAR-∂ and glycogen content/substrate availability. The present study is the first to examine PPAR-∂ activity in skeletal muscle in response to an acute bout of endurance exercise. Our data would suggest that a factor associated with muscle contraction and/or glycogen depletion activates PPAR-∂ and initiates AMPK translocation in skeletal muscle in response to exercise.
authors.affiliation: School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, United Kingdom ; Neurobiology, Physiology and Behavior, University of California Davis, Davis, California, United States of America ; Division of Cell Signalling & Immunology, University of Dundee, Dundee, United Kingdom.
authors.forename: Andrew
authors.initials: A
authors.lastname: Philp
authors.forename: Matthew G
authors.initials: MG
authors.lastname: MacKenzie
authors.forename: Micah Y
authors.initials: MY
authors.lastname: Belew
authors.forename: Mhairi C
authors.initials: MC
authors.lastname: Towler
authors.forename: Alan
authors.initials: A
authors.lastname: Corstorphine
authors.forename: Angela
authors.initials: A
authors.lastname: Papalamprou
authors.forename: D Grahame
authors.initials: DG
authors.lastname: Hardie
authors.forename: Keith
authors.initials: K
authors.lastname: Baar
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D004789:Enzyme Activation; D005260:Female; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism*; D010805:Physical Conditioning, Animal; D051381:Rats; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D047492:Peroxisome Proliferator-Activated Receptors; C501429:Ppargc1a protein, rat; D014157:Transcription Factors; D006003:Glycogen; C543928:Prkaa2 protein, rat; D055372:AMP-Activated Protein Kinases; C568305:Prkaa1 protein, rat; D005947:Glucose