Impact of Genetic Predisposition on Mitochondrial Function in a Rat Model of Aerobic Interval Training

Background: Rats selectively bred for low (LCR) and high intrinsic exercise capacity (HCR) show phenotype-differences. Some studies suggest that this individual exercise capacity is related to cardiovascular disease and it may also affect surgical outcomes. Since cardiovascular function is associated with mitochondrial function we assessed the influence of genetic predisposition for exercise capacity on mitochondrial function in LCR and HCR with and without aerobic interval training (AIT).

Methods: Male LCR and HCR were subjected to AIT adjusted to their individual exercise capacity. After 4 weeks, cardiac function (echocardiography), glucose handling (glucose tolerance test-GTT), citrate synthase (CS) activity and mitochondrial function (respiratory capacity) of heart, gastrocnemius and liver were assessed.

Results: At baseline, LCR displayed significantly lower exercise capacity (LCR vs. HCR velocity: 18 ± 1 vs. 39 ± 1 m/min), higher body weight (336 ± 12 vs. 251 ± 7 g) and higher epididymal fat mass (3.6 ± 0.5 vs. 2.0 ± 0.2 g). GTT revealed no difference between LCR and HCR in basal blood glucose and glucose tolerance. Cardiac morphology was not different between HCR and LCR, but HCR tended toward increased contractility (FS: 41.4 ± 2.8 vs. 45.8 ± 2.8%). Consistent with these observations, LCR presented lower cardiac mitochondrial respiratory capacity (50.4 ± 6.1 vs. 69.7 ± 6.1 natomsO/min/UCS) and also lower activity of citrate synthase in skeletal muscle. There was no difference in liver mitochondria. Four weeks of AIT had no effect on blood glucose or glucose tolerance, but led to a reduction of fat mass in LCR and also to an enhancement of cardiac contractility. Nevertheless, AIT had no influence on mitochondrial citrate synthase activity and only marginal effects on respiratory capacity. With complex II substrate succinate we could measure an unexpected decrease of respiratory capacity in the skeletal muscle and in the liver (skeletal muscle: LCR 83.7 ± 9.4 vs. LCR-AIT 47.7 ± 8.8 natomsO/min/UCS) instead of an improvement trough AIT.

Conclusion: Genetic predisposition for low aerobic exercise capacity is associated with lower cardiac contractility and also with lower mitochondrial function in heart and skeletal muscle. However, four weeks of AIT could in fact slightly improve cardiac contractility in the LCR, but this effect was not associated with an improvement in mitochondrial function.