Sex differences in voluntary running behavior between C57BL/6 and BALB/cJ mouse strains do not correspond to changes...

Exercise adaptations are influenced by sex and genetic background, contributing to variability in metabolic and physiological responses. This study investigates sex and strain-specific differences following voluntary wheel running exercise training in submaximal and maximal oxygen consumption (VO2), respiratory exchange ratio (RER), and body composition in C57BL/6 and BALB/cJ mice. Male and female mice underwent 4 weeks of voluntary wheel running, followed by sub-maximal and maximal treadmill tests in a metabolic chamber. Results indicate differences in running volume across sexes and strains did not consistently predict changes in physiological adaptations. Female C57BL/6 mice, which ran three times more than males on average, exhibited higher submaximal VO2 compared to their male counterparts and to female BALB/cJ mice, despite no differences in RER. In contrast, male BALB/cJ mice, which ran nearly double the distance of their female counterparts, showed a modest decrease in average RER. During maximal treadmill tests, male BALB/cJ mice demonstrated enhanced endurance capacity, characterized by increased distance run and a trend towards lower RER and blood lactate levels at exhaustion, despite no significant changes in VO2 max. Regarding body composition, female C57BL/6 mice experienced a reduction in fat mass and an increase in lean mass, whereas no significant changes were observed in BALB/cJ mice of either sex. The study highlights the need to consider sex- and strain-specific factors when evaluating metabolic and endurance adaptations, and suggests VO₂ testing in mice may not reflect adaptive response to voluntary wheel running.