Differences in Skeletal and Heart Muscle Mitochondrial Function in Response to Intrinsic and Acquired Exercise Capacity

Exercise capacity is a strong predictor of all-cause cardiovascular mortality and morbidity. In contrast, high exercise capacity is protective and “physical fitness” is considered beneficial and to reduce risk in cardiac surgery. These effects may be mediated through mitochondrial function. Importantly, exercise capacity consists of an intrinsic (genetic) and an extrinsic (exercise, environmental) parts. In humans, these two parts cannot be truly separated. The rat model of high (HCR) and low (LCR) capacity runners allows to distinguish between the two parts. We assessed mitochondrial function in this model, specifically investigating mitochondrial respiratory capacity in heart and skeletal muscle.

Exercise capacity of HCR and LCR was determined individually using a ramped test. Mitochondria were isolated from heart, M. gastrocnemius and liver. Citrate synthase activity and protein content were determined photometrically and respiratory capacity was measured using a Clark-type electrode.

At the same age and tibia length, LCR were heavier and had a lower heart to body weight ratio than HCR. Citrate synthase activity was higher in skeletal muscle of HCR, but cardiac citrate synthase was not different between sedentary HCR and LCR. There was no difference in size or complexity of cardiac, skeletal muscle, and liver mitochondria. Respiratory capacity in heart and liver was not different between HCR and LCR with complex I, complex II, complex III, or complex IV substrates. Instead, HCR presented with higher respiratory rates in skeletal muscle with complex I substrates glutamate, pyruvate/malate, or palmitoylcarnitine/malate as substrates. Furthermore, complex II–dependent respiration was increased in HCR as was respiration with complex III or IV substrates DHQ or TMPD ascorbate (HCR vs. LCR glutamate: 107.6 ± 24.0 vs. 63.7 ± 8.0; succinate: 225 ± 28 vs. 136 ± 17; DHQ: 320 ± 93 vs. 184 ± 22; TMPD: 537 ± 61 vs. 320 ± 39 nAO/min/mg protein).

Conclusion: Our data suggest that genetic predisposition for aerobic capacity affects primarily the respiratory capacity of skeletal muscle mitochondria but not of cardiac mitochondria. Thus, beneficial effects of HCR may not be dependent on cardiac mitochondrial function.