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

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 healthy young men performed supervised one-legged knee extensor endurance training for 3 wk. Muscle biopsies were obtained before and 15 h after training in both leas. In response to training the protein content of a 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, γ(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), whereas 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 < 0.005). In agreement with these observations, phosphorylation of α-AMPK (Thr(172)) and of the AMPK target acetyl-CoA carboxylase-β(Ser(221)) increased by 74 and 180%, respectively (both P < 0.001). Essentially similar results were obtained in four additional subjects studied 55 It after training. This study demonstrates that protein content and basal AMPK activity in human skeletal muscle are highly susceptible to endurance exercise training. Except for the increase in gamma1 protein, all observed adaptations to training could be ascribed to local contraction-induced mechanisms, since they did not occur in the contralateral untrained muscle.