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J Physiol Volume 574, Number 1, 125-138, July 1, 2006 DOI: 10.1113/jphysiol.2006.108720
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Higher skeletal muscle {alpha}2AMPK activation and lower energy charge and fat oxidation in men than in women during submaximal exercise

Carsten Roepstorff1, Maja Thiele1, Thore Hillig1, Henriette Pilegaard2, Erik A. Richter1, Jørgen F. P. Wojtaszewski1 and Bente Kiens1

1 The Copenhagen Muscle Research Centre, Department of Human Physiology, Institute of Exercise and Sport Sciences, University of Copenhagen, DK-2100 Copenhagen Ø, Denmark
2 The Copenhagen Muscle Research Centre, Institute of Molecular Biology and Physiology, The August Krogh Building, University of Copenhagen, DK-2100 Copenhagen Ø, Denmark

5'AMP-activated protein kinase (AMPK) is an energy sensor activated by perturbed cellular energy status such as during muscle contraction. Activated AMPK is thought to regulate several key metabolic pathways. We used sex comparison to investigate whether AMPK signalling in skeletal muscle regulates fat oxidation during exercise. Moderately trained women and men completed 90 min bicycle exercise at 60% Formula . Both AMPK Thr172 phosphorylation and {alpha}2AMPK activity were increased by exercise in men (~200%, P < 0.001) but not significantly in women. The sex difference in muscle AMPK activation with exercise was accompanied by an increase in muscle free AMP (~164%, P < 0.01), free AMP/ATP ratio (159%, P < 0.05), and creatine (~42%, P < 0.001) in men but not in women (NS), suggesting that lack of AMPK activation in women was due to better maintenance of muscle cellular energy balance compared with men. During exercise, fat oxidation per kg lean body mass was higher in women than in men (P < 0.05). Regression analysis revealed that a higher proportion of type 1 muscle fibres (~23%, P < 0.01) and a higher capillarization (~23%, P < 0.05) in women than in men could partly explain the sex difference in {alpha}2AMPK activity (r = –0.54, P < 0.05) and fat oxidation (r = 0.64, P < 0.05) during exercise. On the other hand, fat oxidation appeared not to be regulated via AMPK. In conclusion, during prolonged submaximal exercise at 60% Formula , higher fat oxidation in women cannot be explained by higher AMPK signalling but is accompanied by improved muscle cellular energy balance in women probably due to sex specific muscle morphology.

(Received 2 March 2006; accepted after revision 2 April 2006; first published online 6 April 2006)
Corresponding author C. Roepstorff: The Copenhagen Muscle Research Centre, Institute of Exercise and Sport Sciences, Department of Human Physiology, Universitetsparken 13, DK-2100 Copenhagen Ø, Denmark. Email: croepstorff{at}ifi.ku.dk




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