Fiber hypertrophy and increased oxidative capacity can occur simultaneously in pig glycolytic skeletal muscle

An inverse relationship between skeletal muscle fiber cross-sectional area (CSA) and oxidative capacity suggests that 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 (AMPK gamma(R200Q)(3))] or fiber hypertrophy [ryanodine receptor 1 (RyR1(R615C))] to determine if these events occur in parallel. Longissimus muscle was collected from wild-type (control), AMPK gamma(R200Q)(3), RyR1(R615C), and AMPK gamma(R200Q)(3)-RyR1(R615C) pigs. Regardless of AMPK genotype, RyR(R615C) increased fiber CSA by 35%. In contrast, AMPK gamma(R200Q)(3) pig muscle exhibited greater citrate synthase and beta-hydroxyacyl CoA dehydrogenase activity. Isolated mitochondria from AMPK gamma(R200Q)(3) muscle had greater maximal, ADP-stimulated oxygen consumption rate. Additionally, AMPK gamma(R200Q)(3) muscle contained more (similar to 50%) of the mitochondrial proteins succinate dehydrogenase and cytochrome c oxidase and more mitochondrial DNA. Surprisingly, RyR1(R615C) increased mitochondrial proteins and DNA, but this was not associated with improved oxidative capacity, suggesting that altered energy metabolism in RyR1(R615C) muscle influences mitochondrial proliferation and protein turnover. Thus pigs that possess both AMPK gamma 3(R200Q) and RyR(R615C) exhibit increased muscle fiber CSA as well as greater oxidative capacity. Together, our findings support the notion that hypertrophy and enhanced oxidative capacity can occur simultaneously in skeletal muscle and suggest that the signaling mechanisms controlling these events are independently regulated.