Glycogen content regulates peroxisome proliferator activated receptor-∂ (PPAR-∂) activity in rat skeletal muscle.
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 (...
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2013
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oai:doaj.org-article:e5d7fa7b55c24790b3f6d96a1ece29732021-11-18T08:50:36ZGlycogen content regulates peroxisome proliferator activated receptor-∂ (PPAR-∂) activity in rat skeletal muscle.1932-620310.1371/journal.pone.0077200https://doaj.org/article/e5d7fa7b55c24790b3f6d96a1ece29732013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24146969/?tool=EBIhttps://doaj.org/toc/1932-6203Performing 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.Andrew PhilpMatthew G MacKenzieMicah Y BelewMhairi C TowlerAlan CorstorphineAngela PapalamprouD Grahame HardieKeith BaarPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 10, p e77200 (2013) |
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Medicine R Science Q Andrew Philp Matthew G MacKenzie Micah Y Belew Mhairi C Towler Alan Corstorphine Angela Papalamprou D Grahame Hardie Keith Baar Glycogen content regulates peroxisome proliferator activated receptor-∂ (PPAR-∂) activity in rat skeletal muscle. |
| description |
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. |
| format |
article |
| author |
Andrew Philp Matthew G MacKenzie Micah Y Belew Mhairi C Towler Alan Corstorphine Angela Papalamprou D Grahame Hardie Keith Baar |
| author_facet |
Andrew Philp Matthew G MacKenzie Micah Y Belew Mhairi C Towler Alan Corstorphine Angela Papalamprou D Grahame Hardie Keith Baar |
| author_sort |
Andrew Philp |
| title |
Glycogen content regulates peroxisome proliferator activated receptor-∂ (PPAR-∂) activity in rat skeletal muscle. |
| title_short |
Glycogen content regulates peroxisome proliferator activated receptor-∂ (PPAR-∂) activity in rat skeletal muscle. |
| title_full |
Glycogen content regulates peroxisome proliferator activated receptor-∂ (PPAR-∂) activity in rat skeletal muscle. |
| title_fullStr |
Glycogen content regulates peroxisome proliferator activated receptor-∂ (PPAR-∂) activity in rat skeletal muscle. |
| title_full_unstemmed |
Glycogen content regulates peroxisome proliferator activated receptor-∂ (PPAR-∂) activity in rat skeletal muscle. |
| title_sort |
glycogen content regulates peroxisome proliferator activated receptor-∂ (ppar-∂) activity in rat skeletal muscle. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/e5d7fa7b55c24790b3f6d96a1ece2973 |
| work_keys_str_mv |
AT andrewphilp glycogencontentregulatesperoxisomeproliferatoractivatedreceptorpparactivityinratskeletalmuscle AT matthewgmackenzie glycogencontentregulatesperoxisomeproliferatoractivatedreceptorpparactivityinratskeletalmuscle AT micahybelew glycogencontentregulatesperoxisomeproliferatoractivatedreceptorpparactivityinratskeletalmuscle AT mhairictowler glycogencontentregulatesperoxisomeproliferatoractivatedreceptorpparactivityinratskeletalmuscle AT alancorstorphine glycogencontentregulatesperoxisomeproliferatoractivatedreceptorpparactivityinratskeletalmuscle AT angelapapalamprou glycogencontentregulatesperoxisomeproliferatoractivatedreceptorpparactivityinratskeletalmuscle AT dgrahamehardie glycogencontentregulatesperoxisomeproliferatoractivatedreceptorpparactivityinratskeletalmuscle AT keithbaar glycogencontentregulatesperoxisomeproliferatoractivatedreceptorpparactivityinratskeletalmuscle |
| _version_ |
1718421294168408064 |