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Transcriptional regulation of pyruvate dehydrogenase kinase 4 in skeletal muscle during and after exercise

Published online by Cambridge University Press:  05 March 2007

Henriette Pilegaard  and
P. Darrell Neufer
Henriette Pilegaard*
Affiliation:
Copenhagen Muscle Research Centre, August Krogh Institute, University of Copenhagen, Universitetsparken 13, 2100, Copenhagen Ø, Denmark
P. Darrell Neufer
Affiliation:
John B. Pierce Laboratory and Department of Cellular and Molecular Physiology, Yale University, School of Medicine, New Haven, CT 06519, USA
*
*Corresponding author: Dr Henriette Pilegaard Fax: +45 35 32 1567, Email: hpilegaard@aki.ku.dk
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Abstract

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The pyruvate dehydrogenase complex (PDC) has a key position in skeletal muscle metabolism as it represents the entry of carbohydrate-derived fuel into the mitochondria for oxidation. PDC is regulated by a phosphorylation–dephosphorylation cycle, in which the pyruvate dehydrogenase kinase (PDK) phosphorylates and inactivates the complex. PDK exists in four isoforms, of which the PDK4 isoform is predominantly expressed in skeletal and heart muscle. PDK4 transcription and PDK4 mRNA are markedly increased in human skeletal muscle during prolonged exercise and after both short-term high-intensity and prolonged low-intensity exercise. The exercise-induced transcriptional response of PDK4 is enhanced when muscle glycogen is lowered before the exercise, and intake of a low-carbohydrate high-fat diet during recovery from exercise results in increased transcription and mRNA content of PDK4 when compared with intake of a high-carbohydrate diet. The activity of pyruvate dehydrogenase (PDH) is increased during the first 2 h of low-intensity exercise, followed by a decrease towards resting levels, which is in line with the possibility that the increased PDK4 expressed influences the PDH activity already during prolonged exercise. PDK4 expression is also increased in response to fasting and a high-fat diet. Thus, increased PDK4 expression when carbohydrate availability is low seems to contribute to the sparing of carbohydrates by preventing carbohydrate oxidation. The impact of substrate availability on PDK4 expression during recovery from exercise also underlines the high metabolic priority given to replenishing muscle glycogen stores and re-establishing intracellular homeostasis after exercise.

Keywords

Pyruvate dehydrogenase kinase 4Transcriptional regulationSkeletal muscleExercise
Type
Symposium 1: Exercise signalling pathways controlling fuel oxidation during and after exercise
Information
Proceedings of the Nutrition Society , Volume 63 , Issue 2 , May 2004 , pp. 221 - 226
Copyright
Copyright © The Nutrition Society 2004

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