MAIN RESULTS:

1. High fitness is linked to increased skeletal muscle metabolism.

2. Metabolic changes in the heart during heart failure is mainly caused by the disease.
3. Exercise increases metabolism but not high-energy phosphates in failing hearts.

THESIS DEFENCE:

Thesis: MRS-based metabolic profiling of cardiac and skeletal muscle from rats with heart failure, low intrinsic fitness, aging and exercise training
Candidate: Mingshu Shi
Time: December 11, 2019 at 12:15
Place: St. Olavs Hospital, Trondheim University Hospital, Nevro Øst: Auditorium NA
Link to university website (in Norwegian)

SUMMARY:

(1) Two weekly sessions of high-intensity interval training over a long period have marginal impact on leg muscle metabolism in rats. The reason might be that the weekly exercise volume was too low to increase fitness. Rats born with high aerobic capacity had a more favorable metabolic profile than rats born with low aerobic capacity, and ageing also affected the metabolism negatively.

The study includes rats that have been bred to either low or high cardiorespiratory fitness for 30 generations. Rats from both fitness groups were randomly selected to exercise or no exercise, and the researchers measured both fitness and skeletal muscle metabolism after three and eleven months of exercise. High inborn fitness associated with higher levels of glutamine and glutamate and lower levels of lactate, indicating more effective glucose oxidation and higher energy metabolism.

(2) Heart failure is associated with several impairments in cardiac and skeletal muscle metabolism. The changes are linked to reduced contractility, muscle wasting and ineffective, anaerobic energy production. Mingshu’s results indicate that the metabolic changes that occur in the heart during heart failure is mainly caused by the disease, whereas exercise to a larger extent affects skeletal muscle metabolism.

The researchers used advanced nuclear magnetic resonance imaging in six groups of rats, of which half had surgically established heart failure. The healthy and sick rats were randomized to one sedentary and two exercise groups of different intensity. The analyses found several changes in the metabolism of cardiomyocytes in failing rat hearts, and very few of these changes were affected by exercise. On the other hand, mainly exercise training – and not heart failure – altered the metabolite distribution in skeletal muscle.

(3) Six weeks of exercise led to increased ATP levels in cardiomyocytes of rats with heart failure, but the ratio between phospocreatine and ATP did not change. ATP releases energy for muscular work, and phosphocreatine is necessary to rebuild ATP – and the phosphocreatine/ATP ratio expresses the levels of high-energy phosphates within heart muscle cells. Failing hearts have lower levels of high-energy phosphates, giving less potential to generate energy and decreased pumping capacity. Neither moderate exercise nor high-intensity interval training influenced the phosphocreatine/ATP ratio in the study.

However, the exercise increased the maximum oxygen uptake, cardiac performance and mitochondrial respiration, which shows that the exercise actually was effective in improving cardiac metabolism. Thus, the study indicates that the phosphocreatine/ATP ratio is not suited to evaluate the beneficial effects of exercise in the heart. A total of 30 rats were included in the study, of which half had heart failure following a myocardial infarction and were randomized to high-intensity, moderate or no exercise.

REFERENCES:

(1) Shi, M., Ellingsen, Ø., Bathen, T. F., Høydal, M. A., Koch, L. G., Britton, S. L., Wisløff, U., Stølen, T., & Esmaeili, M. (2018). Skeletal muscle metabolism in rats with low and high intrinsic aerobic capacity: Effect of aging and exercise training. PLOS ONE, 13(12), e0208703.

(2) Shi, M., Ellingsen, Ø., Bathen, T. F., Høydal, M. A., Stølen, T., & Esmaeili, M. (2019). The Effect of Exercise Training on Myocardial and Skeletal Muscle Metabolism by MR Spectroscopy in Rats with Heart Failure. Metabolites, 9(3), 53.

(3) Stølen, T., Shi, M., Wohlwend, M., Høydal, M. A., Bathen, T. F., Ellingsen, Ø., & Esmaeili, M. (2019). Effect of exercise training on cardiac metabolism in rats with heart failure. Scandinavian Cardiovascular Journal, 1-8.