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Am J Physiol Endocrinol Metab (November 12, 2003). doi:10.1152/ajpendo.00317.2003
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Submitted on July 10, 2003
Accepted on November 4, 2003

5'AMP-activated protein kinase activity and protein expression are regulated by endurance training in human skeletal muscle

Christian Frosig1*, Sebastian B. Jorgensen1, D. Grahame Hardie2, Erik A. Richter1, and Jorgen F. P. Wojtaszewski1

1 Copenhagen Muscle Research Centre, Institute of Exercise and Sport Sciences, University of Copenhagen, Copenhagen, Denmark
2 Wellcome Trust Biocentre, Division of Molecular Physiology, Faculty of Life Sciences, University of Dundee, Dundee, Scotland, United Kingdom

* To whom correspondence should be addressed. E-mail: Cfrosig{at}ifi.ku.dk.

The 5'AMP-activated protein kinase (AMPK) is proposed to be involved in signaling pathways leading to adaptations in skeletal muscle in response to both a single exercise bout and exercise training. This study investigated the effect of endurance training on protein content of catalytic ({alpha}1, {alpha}2) and regulatory ({beta}1, {beta}2 and {gamma}1, {gamma}2, {gamma}3) subunit isoforms of AMPK as well as on basal AMPK activity in human skeletal muscle. Eight young healthy men performed supervised one-legged knee extensor endurance training for three weeks. Muscle biopsies were obtained before and 15 hours after training in both legs. In response to training the protein content of {alpha}1, {beta}2 and {gamma}1 increased in the trained leg by 41%, 34% and 26%, respectively ({alpha}1 and {beta}2 P<0.005; {gamma}1 P<0.05). In contrast, the protein content of the regulatory {gamma}3 isoform decreased by 62% in the trained leg (P=0.01), while no effect of training was seen for {alpha}2, {beta}1 and {gamma}2. AMPK activity associated with the {alpha}1 and the {alpha}2 isoforms increased in the trained leg by 94% and 49%, respectively (both, P<0.05 ). In agreement with these observations, phosphorylation of {alpha}-AMPK(Thr172) and of the known AMPK target acetyl-CoA carboxylase-{beta}(Ser221) increased by 74% and 180%, respectively (both, P<0.001). This study demonstrates that protein content and basal AMPK activity in human skeletal muscle is highly susceptible to endurance exercise training. Except for the increase in {gamma}1 protein, all observed adaptations to training could be ascribed to local contraction-induced mechanisms, since they did not occur in the contra-lateral untrained muscle.




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