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J Physiol Volume 541, Number 1, 261-271, May 15, 2002 DOI: 10.1113/jphysiol.2002.016832
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Journal of Physiology (2002), 541.1, pp. 261-271
© Copyright 2002 The Physiological Society
DOI: 10.1113/jphysiol.2002.016832

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

Henriette Pilegaard *, Charlotte Keller †, Adam Steensberg †, Jørn Wulff Helge ‡, Bente Klarlund Pedersen †, Bengt Saltin ‡ and P. Darrell Neufer §

The Copenhagen Muscle Research Centre, * The August Krogh Institute, University of Copenhagen, Denmark, † Department of Infectious Diseases, University of Copenhagen, Denmark, ‡ Rigshospitalet, University of Copenhagen, Denmark and § The John B. Pierce Laboratory and Department of Cellular and Molecular Physiology, Yale University, New Haven, CT, USA

Transcription of metabolic genes is transiently induced during recovery from exercise in skeletal muscle of humans. To determine whether pre-exercise muscle glycogen content influences the magnitude and/or duration of this adaptive response, six male subjects performed one-legged cycling exercise to lower muscle glycogen content in one leg and then, the following day, completed 2.5 h low intensity two-legged cycling exercise. Nuclei and mRNA were isolated from biopsies obtained from the vastus lateralis muscle of the control and reduced glycogen (pre-exercise glycogen = 609 ± 47 and 337 ± 33 mmol kg-1 dry weight, respectively) legs before and after 0, 2 and 5 h of recovery. Exercise induced a significant (P < 0.05) increase (2- to 3-fold) in transcription of the pyruvate dehydrogenase kinase 4 (PDK4) and uncoupling protein 3 (UCP3) genes in the reduced glycogen leg only. Although PDK4, lipoprotein lipase (LPL) and hexokinase II (HKII) mRNA were elevated in the reduced glycogen leg before exercise, no consistent difference was found between the two legs in response to exercise. In a second study, six subjects completed two trials (separated by 2 weeks) consisting of 3 h of two-legged knee extensor exercise with either control (398 ± 52 mmol kg-1 dry weight) or low (240 ± 38 mmol kg-1 dry weight) pre-exercise muscle glycogen. Exercise induced a significantly greater increase in PDK4 transcription in the low glycogen (> 6-fold) than in the control (< 3-fold) trial. Induction of PDK4 and UCP3 mRNA in response to exercise was also signficantly higher in the low glycogen (11.4- and 3.5-fold, respectively) than in the control (5.0- and 1.7-fold, respectively) trial. These data indicate that low muscle glycogen content enhances the transcriptional activation of some metabolic genes in response to exercise, raising the possibility that signalling mechanisms sensitive to glycogen content and/or FFA availability may be linked to the transcriptional control of exercise-responsive genes.



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