Glycogen Content Regulates Peroxisome Proliferator Activated Receptor-∂ (PPAR-∂) Activity in Rat Skeletal Muscle

Andrew Philp, Matthew G. MacKenzie, Micah Y. Belew, Mhairi C. Towler, Alan Corstorphine, Angela Papalamprou, D. Grahame Hardie, Keith Baar

Research output: Contribution to journalArticle

22 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere77200
JournalPLoS One
Volume8
Issue number10
DOIs
StatePublished - Oct 17 2013

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Peroxisome Proliferator-Activated Receptors
Glycogen
glycogen
Muscle
skeletal muscle
Rats
Skeletal Muscle
exercise
rats
AMP-activated protein kinase
AMP-Activated Protein Kinases
peroxisome proliferator-activated receptors
Availability
muscles
Mitochondrial Genes
muscle contraction
Chromatin Immunoprecipitation
Skeletal Muscle Fibers
Transcription
Cytoplasmic and Nuclear Receptors

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Philp, A., MacKenzie, M. G., Belew, M. Y., Towler, M. C., Corstorphine, A., Papalamprou, A., ... Baar, K. (2013). Glycogen Content Regulates Peroxisome Proliferator Activated Receptor-∂ (PPAR-∂) Activity in Rat Skeletal Muscle. PLoS One, 8(10), [e77200]. https://doi.org/10.1371/journal.pone.0077200

Glycogen Content Regulates Peroxisome Proliferator Activated Receptor-∂ (PPAR-∂) Activity in Rat Skeletal Muscle. / Philp, Andrew; MacKenzie, Matthew G.; Belew, Micah Y.; Towler, Mhairi C.; Corstorphine, Alan; Papalamprou, Angela; Hardie, D. Grahame; Baar, Keith.

In: PLoS One, Vol. 8, No. 10, e77200, 17.10.2013.

Research output: Contribution to journalArticle

Philp, A, MacKenzie, MG, Belew, MY, Towler, MC, Corstorphine, A, Papalamprou, A, Hardie, DG & Baar, K 2013, 'Glycogen Content Regulates Peroxisome Proliferator Activated Receptor-∂ (PPAR-∂) Activity in Rat Skeletal Muscle', PLoS One, vol. 8, no. 10, e77200. https://doi.org/10.1371/journal.pone.0077200
Philp A, MacKenzie MG, Belew MY, Towler MC, Corstorphine A, Papalamprou A et al. Glycogen Content Regulates Peroxisome Proliferator Activated Receptor-∂ (PPAR-∂) Activity in Rat Skeletal Muscle. PLoS One. 2013 Oct 17;8(10). e77200. https://doi.org/10.1371/journal.pone.0077200
Philp, Andrew ; MacKenzie, Matthew G. ; Belew, Micah Y. ; Towler, Mhairi C. ; Corstorphine, Alan ; Papalamprou, Angela ; Hardie, D. Grahame ; Baar, Keith. / Glycogen Content Regulates Peroxisome Proliferator Activated Receptor-∂ (PPAR-∂) Activity in Rat Skeletal Muscle. In: PLoS One. 2013 ; Vol. 8, No. 10.
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