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

Abstract

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 (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-RyR1R615Cpigs. Regardless of AMPK genotype, RyRR615Cincreased fiber CSA by 35%. In contrast, AMPKγ3R200Qpig muscle exhibited greater citrate synthase and β-hydroxyacyl CoA dehydrogenase activity. Isolated mitochondria from AMPKγ3R200Qmuscle had greater maximal, ADP-stimulated oxygen consumption rate. Additionally, AMPKγ3R200Qmuscle contained more (∼50%) of the mitochondrial proteins succinate dehydrogenase and cytochrome c oxidase and more mitochondrial DNA. Surprisingly, RyR1R615Cincreased mitochondrial proteins and DNA, but this was not associated with improved oxidative capacity, suggesting that altered energy metabolism in RyR1R615Cmuscle influences mitochondrial proliferation and protein turnover. Thus pigs that possess both AMPKγ3R200Qand RyRR615Cexhibit 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.