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

Abstract

-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 AMPK␣2 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 AMPK␣1 and -␣2 double-knockout (mdKO) mice. An acute bout of exercise increased skeletal muscle mRNA content of cytochrome c 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 AMPK␣ wild-type (WT) and mdKO mice. During 4 wk of voluntary running wheel exercise training, the AMPK␣ mdKO mice ran less than WT. Maximal running speed was lower in AMPK␣ mdKO than in WT mice but increased similarly in both genotypes with exercise training. Exercise training increased quadriceps protein content of ubiquinol-cytochrome c reductase core protein 1 (UQCRC1), cytochrome c, hexokinase II, plasma membrane fatty acid-binding protein, and citrate synthase activity more in AMPK␣ 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, AMPK␣1 and -␣2 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.

Skeletal Muscle Insulin Sensitivity Show Circadian Rhythmicity Which Is Independent of Exercise Training Status

“…To confirm the effect of exercise training, protein levels of Hexokinase 2 (HK2) were measured in the incubated skeletal muscles ( Figures 4D–F ). HK2 levels are known to be increased in response to exercise training (Brandauer et al, 2013; Fentz et al, 2015). As expected wheel running increased HK2 levels in both soleus and EDL muscle.…”

New strategies in sport nutrition to increase exercise performance

“…AMPK also plays a key role in controlling running capacity and certain adaptive processes in response to endurance exercise training [25,26]. In a feed forward fashion AMPK can translocate to the nucleus [24,27] where it regulates Histone de-aceytlases, transcription factors and transcriptional co-activators such as histone deacetylase 5 (HDAC5), myocyte enhancing factor 2 (MEF2) and peroxisome proliferator activated receptor-γ co-activator-1α (PGC-1α) respectively (Figure 1) [28][29][30].…”

Molecular Basis of Exercise-Induced Skeletal Muscle Mitochondrial Biogenesis: Historical Advances, Current Knowledge, and Future Challenges

“…Although whole-body deletion of AMP b2 reduces muscle AMPK activity and exercise capacity (Steinberg et al 2010), deletion of the a subunit of AMPK does not impair exercise-induced mitochondrial biogenesis (Jorgensen et al 2005;Fentz et al 2015). These and the results of other studies clearly show that normal responses and adaptations to both acute exercise and chronic exercise training can be seen when one or more key pathways are absent or blocked, indicating that there is both biological redundancy and compensatory up-regulation of other exerciseinduced pathways with putative roles in mitochondrial biogenesis.…”