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Effects of training status on PDH regulation in human skeletal muscle during exercise

  • Muscle Physiology
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Abstract

Pyruvate dehydrogenase (PDH) is the gateway enzyme for carbohydrate-derived pyruvate feeding into the TCA cycle. PDH may play a central role in regulating substrate shifts during exercise, but the influence of training state on PDH regulation during exercise is not fully elucidated. The purpose of this study was to investigate the impact of training state on post-translational regulation of PDHa activity during submaximal and exhaustive exercise. Eight untrained and nine endurance exercise-trained healthy male subjects performed incremental exercise on a cycle ergometer: 40 min at 50% incremental peak power output (IPPO), 10 min at 65% (IPPO), followed by 80% (IPPO) until exhaustion. Trained subjects had higher (P < 0.05) PDH-E1α, PDK1, PDK2, PDK4, and PDP1 protein content as well as PDH phosphorylation and PDH acetylation. Exercising at the same relative intensity led to similar muscle PDH activation in untrained and trained subjects, whereas PDHa activity at exhaustion was higher (P < 0.05) in trained than untrained. Furthermore, exercise induced similar PDH dephosphorylation in untrained and trained subjects, while PDH acetylation was increased (P < 0.05) only in trained subjects. In conclusion, PDHa activity and PDH dephosphorylation were well adjusted to the relative exercise intensity during submaximal exercise. In addition, higher PDHa activity in trained than untrained at exhaustion seemed related to differences in glycogen utilization rather than differences in PDH phosphorylation and acetylation state, although site-specific contributions cannot be ruled out.

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Acknowledgements

We would like to thank the subjects for an extraordinary effort, Professor Graham Hardie for providing anti-bodies, and, in regards to Peter Plomgaard, The Centre for Physical Activity Research (CFAS) is supported by a grant from TrygFonden. The Centre of Inflammation and Metabolism (CIM) was supported by a grant from the Danish National Research Foundation (DNRF55) during the study period.

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Authors and Affiliations

  1. Section for Cell Biology and Physiology, Department of Biology, University of Copenhagen, August Krogh Building, Universitetsparken 13, 2100, Copenhagen, Denmark

    Anders Gudiksen, Lærke Bertholdt, Tomasz Stankiewicz & Henriette Pilegaard

  2. Section of Integrative Physiology, Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark

    Jonas Tybirk & Jens Bangsbo

  3. Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark

    Peter Plomgaard

  4. Centre of Inflammation and Metabolism and the Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

    Peter Plomgaard

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  1. Anders Gudiksen
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Correspondence to Henriette Pilegaard.

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The study was approved by the ethics Committee of Copenhagen and Frederiksberg communities (H-15010768) and was conducted in accordance with the guidelines of the Declaration of Helsinki. The subjects were informed about the experimental protocol, the risks, and discomforts that might occur in association with the intervention and provided written informed consent before the initiation of the study.

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This study is funded by the Danish Ministry of Culture (1095421001), Danish Council for Independent Research (36723-104353), and LB: Danish Diabetes Academy (1105701001).

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Gudiksen, A., Bertholdt, L., Stankiewicz, T. et al. Effects of training status on PDH regulation in human skeletal muscle during exercise. Pflugers Arch - Eur J Physiol 469, 1615–1630 (2017). https://doi.org/10.1007/s00424-017-2019-6

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