title: 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 (AMPKγ3(R200Q))] or fiber hypertrophy [ryanodine receptor 1 (RyR1(R615C))] to determine if these events occur in parallel. Longissimus muscle was collected from wild-type (control), AMPKγ3(R200Q), RyR1(R615C), and AMPKγ3(R200Q)-RyR1(R615C) pigs. Regardless of AMPK genotype, RyR(R615C) increased fiber CSA by 35%. In contrast, AMPKγ3(R200Q) pig muscle exhibited greater citrate synthase and β-hydroxyacyl CoA dehydrogenase activity. Isolated mitochondria from AMPKγ3(R200Q) muscle had greater maximal, ADP-stimulated oxygen consumption rate. Additionally, AMPKγ3(R200Q) muscle contained more (∼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 AMPKγ3(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.
authors.affiliation: Department of Animal and Poultry Sciences, Virginia Tech, Blacksburg, Virginia; and.
authors.forename: T L
authors.initials: TL
authors.lastname: Scheffler
authors.forename: J M
authors.initials: JM
authors.lastname: Scheffler
authors.forename: S
authors.initials: S
authors.lastname: Park
authors.forename: S C
authors.initials: SC
authors.lastname: Kasten
authors.forename: Y
authors.initials: Y
authors.lastname: Wu
authors.forename: R P
authors.initials: RP
authors.lastname: McMillan
authors.forename: M W
authors.initials: MW
authors.lastname: Hulver
authors.forename: M I
authors.initials: MI
authors.lastname: Frisard
authors.forename: D E
authors.initials: DE
authors.lastname: Gerrard
mesh_terms: D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000378:metabolism; D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D001275:ATP Citrate (pro-S)-Lyase / Q000378:metabolism; D000244:Adenosine Diphosphate / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D049108:Cell Enlargement; D004272:DNA, Mitochondrial / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D005260:Female; D005838:Genotype; D006019:Glycolysis; D006984:Hypertrophy; D008297:Male; D008931:Mitochondria, Muscle / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000378:metabolism* / Q000473:pathology; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D010641:Phenotype; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013385:Succinate Dehydrogenase / Q000378:metabolism; D013552:Swine
chemical_list: D004272:DNA, Mitochondrial; D019837:Ryanodine Receptor Calcium Release Channel; D000244:Adenosine Diphosphate; D015094:3-Hydroxyacyl CoA Dehydrogenases; D013385:Succinate Dehydrogenase; D003576:Electron Transport Complex IV; D001275:ATP Citrate (pro-S)-Lyase; D055372:AMP-Activated Protein Kinases
keywords: AMP-activated protein kinase; calcium; mitochondria; ryanodine receptor