An inverse relationship exists between skeletal muscle fiber cross-sectional area (CSA) and oxidative capacity, which suggests muscle fibers hypertrophy at the expense of oxidative capacity. Therefore, our objective was to utilize pigs possessing mutations associated with increased oxidative capacity (AMP-activated protein kinase, AMPKγ3R200Q) or fiber hypertrophy (ryanodine receptor 1, RyR1R615C) to determine if these events occur in parallel. Longissimus muscle was collected from wild type (control), AMPKγ3R200Q, RyR1R615C, and AMPKγ3R200Q- RyR1R615C pigs. Regardless of AMPK genotype, RyRR615C increased fiber CSA by 35%. In contrast, AMPKγ3R200Q pig muscle exhibited greater citrate synthase and β-hydroxyacyl coA dehydrogenase activity. Isolated mitochondria from AMPKγ3R200Q muscle had greater maximal, ADP-stimulated oxygen consumption rate. Additionally, AMPKγ3R200Q muscle contained increased (~50%) content of mitochondrial proteins succinate dehydrogenase and cytochrome c oxidase and greater mitochondrial DNA. Surprisingly, RyR1R615C increased mitochondrial proteins and DNA, but this was not associated with improved oxidative capacity, suggesting that altered energy metabolism in RyR1R615C muscle influences mitochondrial proliferation and protein turnover. Thus, pigs that possess both AMPKγ3R200Q and RyRR615C exhibit increased muscle fiber CSA as well as greater oxidative capacity. Altogether, this supports that hypertrophy and enhanced oxidative capacity can occur simultaneously in skeletal muscle, and suggests the signaling mechanisms controlling these events are independently regulated.
- AMP-activated protein kinase
- ryanodine receptor
- Copyright © 2013, American Journal of Physiology - Cell Physiology