Myocellular adaptations to short-term weighted wheel-running exercise are largely conserved during C26-tumour induction in male and female mice.

Abstract

This study investigated whether performing a translatable murine model of concurrent training after tumour induction affects adaptations in juvenile male and female tumour-bearing mice. Male and female Balb/c mice were injected bilaterally with colon-26 adenocarcinoma (C26) cells or PBS at 8 weeks of age. Half the mice then performed 24 days of voluntary wheel running with progressively increased load (PoWeR training), whereas the rest remained sedentary. Deuterium oxide-based protein synthesis, muscle fibre-type composition and size, protein turnover and mitochondrial markers were assessed 25 days after tumour induction. Average gastrocnemius muscle fibre size was smaller with PoWeR regardless of tumour in males and females, concomitant with a pronounced faster-to-slower fibre-type transition. In male tumour-bearing mice, PoWeR training resulted in greater Redd1, Murf1 and Pgc1α mRNA content than all the other groups, along with lower overall running volume, food consumption and protein synthesis relative to control animals. Molecular measures followed a similar pattern in tumour-bearing female mice with PoWeR, but food consumption, running volume and muscle protein synthesis were maintained. PoWeR training lowered gonadal fat during cancer cachexia in both sexes, and greater heart weight was observed regardless of tumour presence. A negative correlation was found between tumour weight and running distance. Collectively, PoWeR has a similar effect on muscle cellular phenotype in both sexes regardless of tumour presence, and a training effect in male mice with cancer cachexia was present despite molecular and protein synthesis dysregulation.