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Publication
Precancer exercise capacity and metabolism during tumor development coordinate
the skeletal muscle-tumor metabolic competition.
Authors Leitner BP, Fosam AE, Lee WD, Zilinger K, Nakandakari SCBR, Zhang X, Gaspar RC,
Zhu W, Perry CJ, Rabinowitz JD, Perry RJ
Submitted By Submitted Externally on 1/30/2026
Status Published
Journal Proceedings of the National Academy of Sciences of the United States of America
Year 2025
Date Published 12/9/2025
Volume : Pages 122 : e250870712
PubMed Reference 41325517
Abstract Higher exercise capacity and regular exercise training improve cancer prognosis
at all stages of disease. However, the metabolic adaptations to aerobic exercise
training that mediate tumor-host interactions are poorly understood. Here, we
demonstrate that voluntary wheel running slows tumor growth and repartitions
glucose uptake and oxidation to skeletal and cardiac muscle and away from breast
and melanoma tumors in mice. Further, prehabilitation induces repartitioning of
glucose metabolism in obese mice: Uptake and oxidation of glucose are enhanced
in skeletal and cardiac muscle, and reduced in tumors. These increases in muscle
glucose metabolism and reductions in tumor glucose metabolism, correlated with
slower tumor progression. Using [U-13C6] glucose infusion, we show that exercise
increases the fractional contribution of glucose to oxidative metabolism in
muscle while reducing it in tumors, suggesting that aerobic exercise shifts
systemic glucose metabolism away from the tumor microenvironment and toward
metabolically active tissues. Transcriptional analysis revealed downregulation
of mTOR signaling in tumors from exercised mice. Collectively, our findings
suggest that voluntary exercise may suppress tumor progression by enhancing host
tissue glucose oxidation and limiting tumor glucose availability, supporting a
model in which exercise-induced metabolic competition constrains tumor
energetics.




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