Exercise affects mitochondrial function and insulin response in skeletal muscle and fat differentially depending on genetic predisposition

Background: Patients with metabolic syndrome show an increased incidence of heart failure and worse outcome in cardiac surgery. Rats selectively bred for low (LCR) intrinsic aerobic exercise capacity show signs of the metabolic syndrome with reduced systemic insulin sensitivity, compared to their counterparts bred for high intrinsic aerobic capacity (HCR). Exercise has been described to improve survival, muscle function and insulin sensitivity in patients.

Objective: We tested in LCR and HCR the impact of exercise on mitochondrial function in skeletal muscle and fat.

Methods: We applied aerobic interval training to male HCR and LCR rats for 4 weeks. We performed echocardiography to assess cardiac function. Mitochondrial function was assessed using citrate synthase assay as marker. We studied insulin response, glucose metabolism and glucose uptake in exercised and sedentary HCR and LCR rats using the hyperinsulinemic-euglycemic clamp.

Results: After 28 generations of selective breeding, LCR displayed a diabetic phenotype (fasting glucose 4.0 ± 0.1 mmol/l vs. 3.5 ± 0.1, p < 0.01) compared to HCR. LCR and HCR differed in their exercise capacity (LCR vs. HCR 194 ± 26 m vs. 1717 ± 37) and body weight (523 ± 16g vs. 379 ± 19). Echocardiography did not reveal differences in cardiac function or morphology before or after exercise. Exercise decreased body weight in both LCR and HCR (-17.4% vs. -15.7%) and increased heart to body weight (+12.6% vs. +11.4%). Exercise reduced epididymal fat pads and liver weight significantly. LCR displayed higher random glucose, fasting glucose as well as lower glucose infusion rate and glycolysis rate during clamp. These findings were not affected by exercise. Basal mitochondrial citrate synthase activity and insulin induced glucose uptake of skeletal muscle and fat was not different between HCR and LCR. Exercise induced an increase in mitochondrial activity and in 2-deoxy glucose uptake in gastrocnemius of HCR only (31.9%). Similarly, exercise increased mitochondrial activity in epididymal fat of HCR. The increase of 2-DG uptake in epididymal fat was more pronounced in HCR (29.0% LCR vs. 51.5% HCR).

Conclusion: Rats with metabolic syndrome show less response to exercise. Our results suggest that genetic predetermination for aerobic exercise capacity also affects the individual's response to exercise. These findings require further investigation because they may affect the application of exercise in heart failure patients.