AMPKalpha is essential for acute exercise-indueed gene responses but not for exercise training-induced adaptations in mouse skeletal muscle

摘要

Exercise training increases skeletal muscle expression of metabolic proteins improving the oxidative capacity. Adaptations in skeletal muscle by pharmacologically induced activation of 5'-AMP-activated protein kinase (AMPK) are dependent on the AMPKalpha2 subunit. We hypothesized that exercise training-induced increases in exercise capacity and expression of metabolic proteins, as well as acute exercise-induced gene regulation, would be compromised in muscle-specific AMPKalpha1 and -alpha2 double-knockout (mdKO) mice. An acute bout of exercise increased skeletal muscle mRNA content of cytochrome с oxidase subunit I, glucose transporter 4, and VEGF in an AMPK-dependent manner, whereas cluster of differentiation 36 and fatty acid transport protein 1 mRNA content increased similarly in AMPKalpha wild-type (WT) and mdKO mice. During 4 wk of voluntary running wheel exercise training, the AMPKalpha mdKO mice ran less than WT. Maximal running speed was lower in AMPKalpha mdKO than in WT mice but increased similarly in both genotypes with exercise training. Exercise training increased quadriceps protein content of ubiquinol-cyto-chrome с reductase core protein 1 (UQCRC1), cytochrome c, hexoki-nase II, plasma membrane fatty acid-binding protein, and citrate synthase activity more in AMPKalpha WT than in mdKO muscle. However, analysis of a subgroup of mice matched for running distance revealed that only UQCRC1 protein content increased more in WT than in mdKO mice with exercise training. Thus, AMPKalpha1 and -alpha2 subunits are important for acute exercise-induced mRNA responses of some genes and may be involved in regulating basal metabolic protein expression but seem to be less important in exercise training-induced adaptations in metabolic proteins.