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.
Highlights
Skeletal muscle glycogen content determines an individual’s capacity to sustain long duration exercise [1]
Reducing glycogen content prior to exercise increases the activation of key genes involved in mitochondrial biogenesis and lipid oxidation, suggesting that glycogen content regulates the magnitude of skeletal muscle adaptation to endurance exercise [4,5,6]
Rats (n = 4) were separated into five groups consisting of a no exercise control (CON), normal glycogen control (NG-C), normal glycogen exercise (NG-EX), low glycogen control (LG-C) and low glycogen exercise (LG-EX)
Summary
Skeletal muscle glycogen content determines an individual’s capacity to sustain long duration exercise [1]. In the absence of glycogen, muscle increases its metabolic reliance on free fatty acid (FFA) oxidation [2]. This metabolic flexibility indicates that an inverse relationship exists between glycogen content and lipid utilization in skeletal muscle, which might contribute to the increased capacity for fat oxidation in skeletal muscle following endurance training [3]. Reducing glycogen content prior to exercise increases the activation of key genes involved in mitochondrial biogenesis and lipid oxidation, suggesting that glycogen content regulates the magnitude of skeletal muscle adaptation to endurance exercise [4,5,6]. Following the training period there was a greater increase in time to exhaustion in the low glycogen group and increased activity of the b-oxidation and TCA enzymes (3hydroxyacyl-CoA dehydrogenase (HAD) and citrate synthase (CS)) [7]
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