Voluntary wheel running selectively preserves skeletal muscle during pancreatic cancer cachexia despite persistent systemic alterations
- 1University Rennes 2
Abstract
Background Pancreatic ductal adenocarcinoma (PDAC) is frequently associated with cancer cachexia, involving alterations across multiple physiological systems. Whether distinct exercise paradigms similarly influence these compartments remains unclear. We compared voluntary wheel running (VWR) and treadmill running (TR) using an integrative physiological approach in a murine model of pancreatic cancer cachexia. Methods Male C57BL/6J mice bearing UN-KC-6141 pancreatic tumor cells were allocated to inactive control (CaCTL), VWR or TR groups and compared with healthy controls. Tumor progression, body composition, skeletal muscle, adipose tissue, hepatic metabolism, systemic inflammation, energy expenditure and behavior were assessed. Analysis of covariance determined whether tissue-mass differences remained evident after adjustment for tumor burden. Results UN-KC-6141 tumors induced a systemic cachectic phenotype involving skeletal muscle and adipose tissue wasting, hepatic metabolic remodeling, systemic inflammation and behavioral alterations. VWR slowed tumor growth, reduced final tumor mass, improved the body-weight trajectory and preserved lean and skeletal muscle mass, whereas TR did not reproduce these adaptations. Greater gastrocnemius mass with VWR remained evident after adjustment for tumor mass, indicating that reduced tumor burden alone was insufficient to account for muscle preservation. In contrast, adipose tissue wasting, hepatic metabolic remodeling and systemic inflammation remained largely unaffected. TR was also associated with a less favorable body-weight trajectory and greater fat mass loss than in inactive tumor-bearing mice. Exploratory metabolic phenotyping revealed distinct feeding, sleep and resting energy expenditure patterns between the two exercise paradigms. Conclusions VWR selectively preserved skeletal muscle within a persistently altered systemic environment, whereas the TR protocol used here did not reproduce these adaptations. These findings reveal tissue-specific exercise responsiveness during pancreatic cancer cachexia and highlight exercise paradigm characteristics as determinants of tumor-host adaptation.
Related
- Therapy-Persistent Leukemia Is Selectively Vulnerable to SLC23A1 Restoration via Targeting KHSRP
- Voluntary physical activity and pharmacological treatment with the Ginkgo biloba extract EGb 761 alleviate regional alterations in cerebral synaptic density and improve behavioral recovery after unilateral labyrinthectomy in the rat
- Chicoric acid-rich extract of Cichorium intybus seeds (CAREOCI) preserves pancreatic β-cell function under glucotoxic stress through modulation of MAFA, DYRK1A, cell cycle, apoptosis, and mitochondrial dysfunction
- MELATONIN SELECTIVELY ATTENUATES HISTOPATHOLOGICAL ALTERATIONS IN A HUMANIZED MOUSE MODEL OF SICKLE CELL ANEMIA
- ERGOTHIONEINE PRESERVES SPLENIC ARCHITECTURE AND ATTENUATES HEPATIC HISTOPATHOLOGICAL ALTERATIONS IN A HUMANIZED MOUSE MODEL OF SICKLE CELL ANEMIA
BibTeX
@misc{richard2026voluntary,
title = {{Voluntary wheel running selectively preserves skeletal muscle during pancreatic cancer cachexia despite persistent systemic alterations}},
author = {C. Richard and A. Dieumegard and L.-A. Cavrois and L. Lefeuvre-Orfila and B. Martin and L. Rouviere and S. Servais and M. Vlach and G. Angenard and C. Ribault and A. Corlu and P. Loyer and A. Rebillard},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.14.758481},
url = {https://www.biorxiv.org/content/10.64898/2026.10.14.758481v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Voluntary wheel running selectively preserves skeletal muscle during pancreatic cancer cachexia despite persistent systemic alterations
AU - C. Richard
AU - A. Dieumegard
AU - L.-A. Cavrois
AU - L. Lefeuvre-Orfila
AU - B. Martin
AU - L. Rouviere
AU - S. Servais
AU - M. Vlach
AU - G. Angenard
AU - C. Ribault
AU - A. Corlu
AU - P. Loyer
AU - A. Rebillard
PY - 2026
DA - 2026/10/14
PB - bioRxiv
DO - 10.64898/2026.10.14.758481
UR - https://www.biorxiv.org/content/10.64898/2026.10.14.758481v1
AB - Background Pancreatic ductal adenocarcinoma (PDAC) is frequently associated with cancer cachexia, involving alterations across multiple physiological systems. Whether distinct exercise paradigms similarly influence these compartments remains unclear. We compared voluntary wheel running (VWR) and treadmill running (TR) using an integrative physiological approach in a murine model of pancreatic cancer cachexia. Methods Male C57BL/6J mice bearing UN-KC-6141 pancreatic tumor cells were allocated to inactive control (CaCTL), VWR or TR groups and compared with healthy controls. Tumor progression, body composition, skeletal muscle, adipose tissue, hepatic metabolism, systemic inflammation, energy expenditure and behavior were assessed. Analysis of covariance determined whether tissue-mass differences remained evident after adjustment for tumor burden. Results UN-KC-6141 tumors induced a systemic cachectic phenotype involving skeletal muscle and adipose tissue wasting, hepatic metabolic remodeling, systemic inflammation and behavioral alterations. VWR slowed tumor growth, reduced final tumor mass, improved the body-weight trajectory and preserved lean and skeletal muscle mass, whereas TR did not reproduce these adaptations. Greater gastrocnemius mass with VWR remained evident after adjustment for tumor mass, indicating that reduced tumor burden alone was insufficient to account for muscle preservation. In contrast, adipose tissue wasting, hepatic metabolic remodeling and systemic inflammation remained largely unaffected. TR was also associated with a less favorable body-weight trajectory and greater fat mass loss than in inactive tumor-bearing mice. Exploratory metabolic phenotyping revealed distinct feeding, sleep and resting energy expenditure patterns between the two exercise paradigms. Conclusions VWR selectively preserved skeletal muscle within a persistently altered systemic environment, whereas the TR protocol used here did not reproduce these adaptations. These findings reveal tissue-specific exercise responsiveness during pancreatic cancer cachexia and highlight exercise paradigm characteristics as determinants of tumor-host adaptation.
ER -