Chronic β2-adrenoceptor agonist treatment alters muscle proteome and functional adaptations induced by high intensity training in young men

Although the effects of training have been studied for decades, data on muscle proteome signature remodelling induced by high intensity training in relation to functional changes in humans remains incomplete. Likewise, beta(2)-agonists are frequently used to counteract exercise-induced bronchoconstriction, but the effects beta(2)-agonist treatment on muscle remodelling and adaptations to training are unknown. In a placebo-controlled parallel study, we randomly assigned 21 trained men to 4 weeks of high intensity training with (HIT+beta(2)A) or without (HIT) daily inhalation of beta(2)-agonist (terbutaline, 4 mgdose(-1)). Of 486 proteins identified by mass-spectrometry proteomics of muscle biopsies sampled before and after the intervention, 32 and 85 were changing (false discovery rate (FDR) <= 5%) with the intervention in HIT and HIT+beta(2)A, respectively. Proteome signature changes were different in HIT and HIT+beta(2)A (P=0.005), wherein beta(2)-agonist caused a repression of 25 proteins in HIT+beta(2)A compared to HIT, and an upregulation of 7 proteins compared to HIT. beta(2)-Agonist repressed or even downregulated training-induced enrichment of pathways related to oxidative phosphorylation and glycogen metabolism, but upregulated pathways related to histone trimethylation and the nucleosome. Muscle contractile phenotype changed differently in HIT and HIT+beta(2)A (P <= 0.001), with a fast-to-slow twitch transition in HIT and a slow-to-fast twitch transition in HIT+beta(2)A. beta(2)-Agonist attenuated training-induced enhancements in maximal oxygen consumption (P <= 0.01) and exercise performance (6.1 vs. 11.6%, P <= 0.05) in HIT+beta(2)A compared to HIT. These findings indicate that daily beta(2)-agonist treatment attenuates the beneficial effects of high intensity training on exercise performance and oxidative capacity, and causes remodelling of muscle proteome signature towards a fast-twitch phenotype.