Energy metabolism in skeletal muscle: mechanistic insights into mitochondrial function and growth

Skeletal muscle metabolism is critical to understanding the efficiency of muscle growth for the global meat industry. As such, there are many contributing factors that can influence muscle growth yet there are still basic molecular mechanisms that remain unexplored. Specifically, the involvement of mitochondria during skeletal muscle hypertrophy. Armed with this goal, we sought to target the fundamental aspects of how the mitochondria facilitate muscle growth in various livestock species. We showed that skeletal muscle mitochondrial abundance through mitochondrial DNA (mtDNA) and protein may not be sufficient to determine their functionality significance in muscle of livestock. Particularly, avian mitochondrial function is independent of absolute mtDNA and protein abundance. However, porcine and bovine muscle mitochondria abundance correlated with skeletal muscle type function. These findings confirm the importance of evaluating mitochondrial content and function to determine their overall contribution to muscle metabolism. To investigate the role of the mitochondria during muscle growth, we utilized beta-adrenergic agonists (BAA) fed pigs harboring the constitutively active adenosine monophosphate activated protein kinase mutation (AMPKγ3R200Q) that results in greater oxidative capacity in a habitually glycolytic skeletal muscle. We discovered BAA supplementation stimulates beta-1 adrenergic receptor gene expression and impacts mitochondrial respiration. Interestingly, BAA feeding had more effect on control pig muscle compared to that of pigs harboring the AMPKγ3R200Q mutation. This further suggests BAA-induced muscle hypertrophy is not as effective on muscles with increased oxidative capacity. To expand our knowledge on muscle hypertrophy, we assessed the impact of finishing feeding regimes on beef cattle muscle energy utilization. We showed that mitochondria from muscle of forage-maintained cattle have greater respiration compared to mitochondria of those carbohydrate-maintained cattle and glycolytic muscles. These data indicate that diet impacts skeletal muscle metabolism specifically in the ability of mitochondria to utilize long- and short-chain fatty acids. In addition to studying muscle hypertrophy in livestock, we generated knockout mouse models to assess the necessity of mitochondria in skeletal muscle during post-weaning growth. We found that reduced mtDNA content has a mild impact on mitochondrial protein expression and functionality, yet appears accumulative in its impact on skeletal muscle as reflected in final body weight and lean mass of knockout mice. Finally, we created a knockout mouse lacking a functional mitochondrial ATP synthase subunit beta gene and found that the ability of the mitochondria to generate ATP was not requisite for post-weaning growth of muscles expressing myosin light chain-1. In summary, mitochondria contribute significantly to overall skeletal muscle metabolism yet may not be required for optimal muscle growth prior to maturity. Further understanding of the molecular mechanisms necessary for optimal muscle growth is necessary to provide additional opportunities to improve efficiency of livestock growth.

Name thesis:degree_name

Doctor of Philosophy

Level thesis:degree_level

doctoral

Discipline thesis:degree_discipline

Animal and Poultry Sciences

Department dc:contributor.department

Animal and Poultry Sciences

Grantor dc:publisher

Virginia Tech

Year dc:date.issued

2026

Author dc:creator

• Yen, Con-Ning

Chair dc:contributor.committeechair

• Gerrard, David E.

Committee members dc:contributor.committeemember

• Rhoads, Robert P.
• Drake, Joshua Chadwick
• Shi, Tim Hao
• Johnson, Sally E.

• skeletal muscle
• energy metabolism
• mitochondria

Statement dc:rights

• In Copyright

Licence dc:rights.uri

• http://rightsstatements.org/vocab/InC/1.0/

Language dc:language.iso

en

Dc Identifier Other

vt_gsexam:45495

OAI identifier oai:identifier

oai:vtechworks.lib.vt.edu:10919/140699