Abstract
An increase in Mechanistic Target of Rapamycin Complex I (mTORC1) kinase activity stimulates muscle protein synthesis in response to amino acids, growth factors, energy, and mechanical stimuli. We previously found muscle hypertrophy and increased mitochondrial respiration in resting mice with chronically active mTORC1 (i.e., an inducible skeletal muscle specific DEPDC5 knockout (KO) model), but no improvement in muscle quality and function. PURPOSE: The purpose of this study was to determine the metabolic profile of skeletal muscle in DEPDC5 KO and wild-type (WT) male and female mice following 1-hour of treadmill exercise. METHODS: Targeted metabolomics was performed on quadricep muscle, with a total of 272 polar metabolites being detected. RESULTS: Acute exercise induced a differential response in metabolites related to fuel utilization, amino acid metabolism, and nucleotide metabolism between mice with hyperactive mTORC1 and wild-type control mice. Genotype had a much stronger impact than exercise, with predominantly decreased metabolites in sedentary mice that were partially restored with exercise. CONCLUSION: We conclude that increased mTORC1 signaling modifies the skeletal muscle metabolome in response to exercise, indicating that mTORC1 signaling plays a key role in regulating muscle metabolism. Understanding these mechanisms could lead to the development of strategies for restoring mTORC1 signaling in conditions associated with chronically active mTORC1 signaling such as aging and cancer.
Recommended Citation
Kalenta, Hanna; Kilroe, Sean P.; Romsdahl, Trevor B.; Marchant, Erik D.; Maroto, Rosario; Linares, Jennifer J.; Russell, William K.; and Rasmussen, Blake B.
(2025)
"Muscle Metabolic Profile Following Acute Exercise in Mice with Constitutively Active mTORC1,"
International Journal of Exercise Science: Conference Proceedings: Vol. 2:
Iss.
17, Article 38.
Available at:
https://digitalcommons.wku.edu/ijesab/vol2/iss17/38