Female Rats with Genetically Determined Exercise Capacity are Running Faster than Their Male Counterparts despite Reduced Mitochondrial Function

In many pathologies, especially cardiovascular diseases, sex differences exist. It is known that adaptation to exercise training differs between men and women. High exercise capacity is associated with lower risk for cardiovascular diseases and better surgical outcome. Furthermore, higher exercise capacity is related to higher mitochondrial function. In a rat model of genetically determined high or low exercise capacity (HCR/LCR), differences exist regarding their lifespan and metabolic function. Our aim was to compare mitochondrial function in male versus female HCR and LCR rats. Female and male HCR and LCR rats were assessed at 24 months of age. We characterized weights, glucose tolerance, exercise capacity, citrate synthase activity, mitochondrial morphology, and respiratory capacity in cardiac and skeletal muscle interfibrillar (IFM) and subsarcolemmal (SSM) mitochondria, isolated with differential centrifugation. Female HCR and LCR presented with lower body weight and skeletal muscle weight. Glucose tolerance was lower in male rats and lowest in LCR compared with HCR. Independently of the genetic phenotype females showed a higher exercise capacity than males. This was more pronounced in HCR. Citrate synthase activity in cardiac tissue was comparable in all groups. In skeletal muscle female HCR presented with lower citrate synthase activity compared with male HCR (male vs. female: 42.7 ± 8.2 vs. 25.8 ± 4.8 U/g wet weight). Morphology of IFM did not differ between the groups. Size and internal complexity of SSM in females was reduced compared with males in heart and skeletal muscle. Mitochondrial maximal respiratory capacity was lower in LCR compared with HCR (skeletal muscle: female HCR versus female LCR: 185 ± 13 versus 100 ± 11 natomsO/min/mg protein). In addition, females had lower respiratory capacity rates in cardiac SSM and skeletal muscle IFM in HCR (heart: male versus female: 510 ± 46 versus 391 ± 36 natomsO/min/mg protein) as well as in LCR rats. Despite lower mitochondrial respiratory capacity ex vivo females present with higher exercise capacity in vivo than males. Thus, cooperative systems interplay in vivo may be more efficient in females.