Trening og energistoffskifte
Low aerobic exercise capacity is a strong independent predictor of cardiovascular disease and premature death. This study was to determine the metabolic profiles in a rat model of low capacity runners (LCR) and high capacity runners (HCR) and to investigate the variation with aerobic capacity, aging, and exercise training on muscle metabolism.Recent studies have shown that exercise capacity is an independent predictor of cardiovascular disease and premature death, perhaps stronger than other established risk factors, such as age, smoking, hypercholesterolemia, hypertension, and diabetes. Low exercise capacity can result from both intrinsic factors (e.g., genetics, preterm birth) and from acquired factors (inactivity, unhealthy eating, environmental factors) increasing the risk of metabolic syndromes (e.g., diabetes, obesity, etc.) . Several metabolic pathways, such as glucose utilization, citrate acid cycle, amino acid utilization or lipid metabolism in skeletal muscle, could be linked to exercise capacity, and thus to pathogenic processes . In cardiovascular diseases such as heart failure, several lines of evidence suggest that exercise training benefits these patients physiologically . The benefits of exercise training include improved in myocardial oxidative metabolism, ventricular function, coronary circulation . Exercise capacity and cardiovascular fitness are associated with metabolic reprogramming and enhances the function of skeletal muscle . However, it has not been investigated to what extent the beneficial effects are dependent on characteristics of the individual, such as age and intrinsic capacity for exercise. To get a better understanding of the relationship between skeletal muscle metabolism and exercise capacity related diseases, a rat model of low versus high aerobic capacity runners (LCR/HCR), was applied to investigate energy metabolism in skeletal muscle, as well as the effect of interventions on bioenergetics . By utilizing this model, we hypothesized that age, intrinsic running capacity and exercise training would affect skeletal muscle metabolism. Furthermore, we hypothesized that the altered metabolism, would be related to aerobic energy metabolism and share similarities with the metabolic syndrome pathogenesis as described before . Therefore, we investigated the metabolic profiles in skeletal muscle of LCR and HCR rats by using metabolomics based on magnetic resonance spectroscopy (MRS), and correlated with, whole-body oxygen consumption (VO2max). The result showed that sedentary HCR rats had 54% and 30% higher VO2max compared to sedentary LCR rats at 9-months and 18-months, respectively. In HCR, exercise increased running speed significantly and VO2max was higher in 9-month old exercised for 3 months compared to sedentary counterparts. In LCR, changes were small and did not reach the level of significance. The metabolic profile was significantly different in the LCR sedentary group compared to the HCR sedentary group at the age of 9 and 18 months, with higher glutamine and glutamate levels and lower lactate level in HCR. Irrespective of fitness level, aging was associated with a change in the metabolic profile, especially pronounced with increased concentrations of glycerophosphocholine with age. Exercise training did not influence metabolic profiles in LCR or HCR rats at any age. In conclusion, the metabolic profiles were significantly different between HCR and LCR rats and between 9-month and 18-months rats. Interval training twice a week induced limited effects by only improving VO2max level in 9-month HCR rats and non in metabolic profile.
Heart failure (HF) impairs resting myocardial energetics and exercise training is included in most rehabilitation programs and benefits HF patients. The aim of this study was to investigate the effects of exercise training at different intensities in HF rats.In this study, we firstly used rats underwent myocardial infarctions or sham operations and were separated into three exercise groups: sedentary control, moderate intensity, or high intensity. The impact of HF and exercise training on energy metabolism was evaluated by 31P MRS and mitochondrial respirometry. The concentrations of key bioenergetic metabolites phosphocreatine (PCr), adenosine triphosphate (ATP), and inorganic phosphate (Pi) were quantified by MRS. VO2max was measured by treadmill respirometry. From the methodology, we obtained the data from whole body oxygen consumption test, in vitro MR spectroscopy and in situ mitochondrial function. In summary, our study investigated the effect of different exercise training intensities on energy metabolism in HF. Heart failure induced a significant reduction in PCr/ATP ratio, the clinically examined biomarker of heart failure, in our HF rat models. This reduction was induced by decreased level of PCr with unchanged ATP levels. As we hypothesized, the energy metabolism was impaired in HF rats and could be recovered after exercise training. This is reflected in relatively increased ATP level. Furthermore, the reduced mitochondrial respiratory capacity in HF rats was partially recovered by high-intensity exercise training, through increased complex I respiration. These adaptations were associated with an improvement in VO2max and running capacity. The experimental rat model mimics human physiology and helps us to further understand the mechanism of cardiac performance improvement by exercise training. Taken together, our results show that the repressed PCr levels in MI hearts may not be crucial to exercise adaptation. Exercise training in our HF rat model resulted in significant improvement in exercise capacity, and modulated mitochondrial function, VO2max, and ATP availability through mitochondrial respiration. These findings support the hypothesis that exercise training could have potentially important implications in clinical treatment for patients with HF. Considering the close association between ATP and PCr transfer, the molecular mechanism in which unchanged PCr and increased ATP synthesis could improve energy metabolism post exercise training remains to be investigated.
Information on energy metabolism from magnetic resonance spectroscopy may reveal important details of heart muscle function.The aim of the present project is to determine whether magnetic resonance spectroscopy (MRS) can be used to evaluate the function of the heart muscle. Previous studies have shown that reduced heart muscle function in heart failure is associated with impaired energy metabolism in the heart, and that this can be detected noninvasively by this method. We have already shown that exercise training improves heart muscle function in heart failure. Therefore, the working hypothesis of the present PhD project was that exercise training improves cardiac function and partially restores myocardial energy metabolism. If this is the case, then in vivo MRS could be used as a noninvasive method to evaluate the effects of training and other treatments in heart failure patients. The project started in May 2015, and the first part was to determine the changes in energy metabolism in an experimental model of heart failure and exercise training in rats. Analysis of tissue samples from the heart muscle showed that myocardial infarction and exercise training influenced the level of two high-energy phosphor metabolites (phosphocreatine and adenosine triphosphate). It is likely that these changes resulted from reduced mitochondrial function, which is a central part of energy metabolism. These early results have been reported in a manuscript that has been submitted to the Journal of Applied physiology. The next part of the project will be to test out whether we are able to detect similar changes using noninvasive MRS measurements in the same model. Even if there is still much work to do, the project is proceeding according to plan.