Sex differences in voluntary running behavior between C57BL/6 and BALB/cJ mouse strains do not correspond to changes in VO2 and RER.

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.