Reduced carbohydrate availability enhances exercise-induced p53 signaling in human skeletal muscle: implications for mitochondrial biogenesis.

@article{Bartlett2013ReducedCA,
  title={Reduced carbohydrate availability enhances exercise-induced p53 signaling in human skeletal muscle: implications for mitochondrial biogenesis.},
  author={Jonathan D. Bartlett and Jari Louhelainen and Zafar Iqbal and Andrew J.R. Cochran and Martin J. Gibala and Warren Gregson and Graeme L. Close and Barry Drust and James P. Morton},
  journal={American journal of physiology. Regulatory, integrative and comparative physiology},
  year={2013},
  volume={304 6},
  pages={
          R450-8
        }
}
The mechanisms that regulate the enhanced skeletal muscle oxidative capacity observed when training with reduced carbohydrate (CHO) availability are currently unknown. The aim of the present study was to test the hypothesis that reduced CHO availability enhances p53 signaling and expression of genes associated with regulation of mitochondrial biogenesis and substrate utilization in human skeletal muscle. In a repeated-measures design, muscle biopsies (vastus lateralis) were obtained from eight… 
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References

SHOWING 1-10 OF 66 REFERENCES

Effect of carbohydrate ingestion on exercise-induced alterations in metabolic gene expression.

Glucose ingestion attenuated the exercise-induced increase in PDK-4 and UCP3 mRNA and PGC-1 mRNA, suggesting that glucose availability can modulate the effect of exercise on metabolic gene expression.

Reduced carbohydrate availability does not modulate training-induced heat shock protein adaptations but does upregulate oxidative enzyme activity in human skeletal muscle.

Data provide the first evidence that in whole body exercise conditions, carbohydrate availability appears to have no modulating effect on training-induced increases of the HSP content of skeletal muscle.

An acute bout of high-intensity interval training increases the nuclear abundance of PGC-1α and activates mitochondrial biogenesis in human skeletal muscle.

Findings support the hypothesis that an acute bout of low-volume HIT activates mitochondrial biogenesis through a mechanism involving increased nuclear abundance of PGC-1α.

Fat adaptation followed by carbohydrate restoration increases AMPK activity in skeletal muscle from trained humans.

It is demonstrated that AM PK-alpha1 and AMPK-alpha2 activity and fuel selection in skeletal muscle in response to exercise can be manipulated by diet and/or the interactive effects of diet and exercise training.

Intensified exercise training does not alter AMPK signaling in human skeletal muscle.

It is indicated that, in well-trained individuals, short-term HIT improves metabolic control but does not blunt AMPK signaling in response to intense exercise.

Role of p53 in mitochondrial biogenesis and apoptosis in skeletal muscle.

A novel role for p53 in maintaining mitochondrial biogenesis, apoptosis, and performance in skeletal muscle is illustrated by observing diminished mitochondrial content in mixed muscle and lowered peroxisome proliferator-activated receptor-gamma (PPARgamma) coactivator (PGC)-1alpha protein levels in gastrocnemius muscle.

p53 Improves Aerobic Exercise Capacity and Augments Skeletal Muscle Mitochondrial DNA Content

The current findings indicate that p53 promotes aerobic metabolism and exercise capacity by using different mitochondrial genes and mechanisms in a tissue-specific manner.

Carbohydrate feeding during recovery alters the skeletal muscle metabolic response to repeated sessions of high-intensity interval exercise in humans.

Evidence is provided that p38 MAPK is a nutrient-sensitive signaling molecule that could be involved in the altered skeletal muscle adaptive response reported after exercise training under conditions of restricted CHO intake, but further research is required to confirm this hypothesis.

Human skeletal muscle PDH kinase activity and isoform expression during a 3-day high-fat/low-carbohydrate diet.

The results suggest that the continuing increase in PDK activity over the 3-day HF/LC diet is not due to increasing PDK protein beyond 1 day, and could be due to the contribution of another isoform to the totalPDK activity or to a continual increase inPDK4 or PDK2 specific activity.

Influence of pre‐exercise muscle glycogen content on exercise‐induced transcriptional regulation of metabolic genes

Low muscle glycogen content enhances the transcriptional activation of some metabolic genes in response to exercise, raising the possibility that signalling mechanisms sensitive to glycogencontent and/or FFA availability may be linked to the transcriptionAL control of exercise‐responsive genes.
...