Intensified exercise training does not alter AMPK signaling in human skeletal muscle

1 Exercise Metabolism Group, School of Medical Sciences, RMIT University, Victoria 3083; 2 St. Vincent's Institute of Medical Research, and Department of Medicine, University of Melbourne, Fitzroy, Victoria 3065; and 3 Muscle, Ions and Exercise Group, School of Human Movement, Recreation and Performance, Centre for Rehabilitation, Exercise and Sports Science, Melbourne, Victoria University of Technology, Victoria 3011, Australia Submitted 14 October 2003 ; accepted in final form 14 December 2003 The AMP-activated protein kinase (AMPK) cascade has been linked to many of the acute effects of exercise on skeletal muscle substrate metabolism, as well as to some of the chronic training-induced adaptations. We determined the effect of 3 wk of intensified training (HIT; 7 sessions of 8 x 5 min at 85% O 2 peak ) in skeletal muscle from well-trained athletes on AMPK responsiveness to exercise. Rates of whole body substrate oxidation were determined during a 90-min steady-state ride (SS) pre- and post-HIT. Muscle metabolites and AMPK signaling were determined from biopsies taken at rest and immediately after exercise during the first and seventh HIT sessions, performed at the same (absolute) pre-HIT work rate. HIT decreased rates of whole body carbohydrate oxidation ( P < 0.05) and increased rates of fat oxidation ( P < 0.05) during SS. Resting muscle glycogen and its utilization during intense exercise were unaffected by HIT. However, HIT induced a twofold decrease in muscle [lactate] ( P < 0.05) and resulted in tighter metabolic regulation, i.e., attenuation of the decrease in the PCr/(PCr + Cr) ratio and of the increase in [AMP free ]/ATP. Resting activities of AMPK 1 and - 2 were similar post-HIT, with the magnitude of the rise in response to exercise similar pre- and post-HIT. AMPK phosphorylation at Thr 172 on both the 1 and 2 subunits increased in response to exercise, with the magnitude of this rise being similar post-HIT. Acetyl-coenzyme A carboxylase- phosphorylation was similar at rest and, despite HIT-induced increases in whole body rates of fat oxidation, did not increase post-HIT. Our results indicate that, in well-trained individuals, short-term HIT improves metabolic control but does not blunt AMPK signaling in response to intense exercise. adenosine 5'-monophosphate-activated protein kinase; acetyl-coenzyme A carboxylase; glycogen; fat metabolism Address for reprint requests and other correspondence: J. A. Hawley, School of Medical Sciences, RMIT Un