Erythropoietic adaptations to endurance training

Erythropoietic adaptations involving the oxygen dissociation curve (ODC) and erythropoietin production have been implicated in the etiology of reduced blood haemoglobin concentrations in sportspersons (known as sports anaemia). A significant increase in the half-saturation pressure indicating a right-shift in the ODC was measured in 34 male [25.8-27.4 mmHg (3.44-3.65 kPa)] and 16 female (25.8-27.7 mmHg (3.44-3.69 kPa)] trained distance runners (P less than 0.01 for both genders) after completing a standard 42-km marathon. Erythrocyte 2,3-diphosphoglycerate concentrations measured concurrently were unaltered by exercise, although consistently higher in the female compared to the male athletes (P less than 0.05). The serum erythropoietin (EPO) concentrations of 15 male triathletes (26.3 U.ml-1) were significantly lower than those of 45 male distance runners (31.6 U.ml-1; P less than 0.05). However, the mean serum EPO concentrations of male and female athletes engaged in a variety of sports were not different from those of sedentary control subjects of both sexes (26.5-35.3 U.ml-1). Furthermore, the serum EPO concentrations were unaltered after prolonged strenuous exercise in 20 male marathon runners. These data suggest that the haematological status of these endurance athletes is in fact normal and that the observed shift in the ODC, while providing a physiological advantage during exercise, has no measurable effect on the erythropoietic drive.     

Early muscular and metabolic adaptations to prolonged exercise training in humans

A short-term training program involving 2 h of daily exercise at 59% of peak O2 uptake (VO2max) repeated for 10-12 consecutive days was employed to determine the significance of adaptations in energy metabolic potential on alterations in energy metabolism and substrate utilization in working muscle. The initial VO2max determined before training on the eight male subjects was 53.0 +/- 2.0 (SE) ml.kg-1.min-1. Analysis of samples obtained by needle biopsy from the vastus lateralis muscle before exercise (0 min) and at 15, 60, and 99 min of exercise indicated that on the average training resulted (P less than 0.05) in a 6.5% higher concentration of creatine phosphate, a 9.9% lower concentration of creatine, and a 39% lower concentration of lactate. Training had no effect on ATP concentration. These adaptations were also accompanied by a reduction in the utilization in glycogen such that by the end of exercise glycogen concentration was 47.1% higher in the trained muscle. Analysis of the maximal activities of representative enzymes of different metabolic pathways and segments indicated no change in potential in the citric acid cycle (succinate dehydrogenase, citrate synthase), beta-oxidation (3-hydroxyacyl CoA dehydrogenase), glucose phosphorylation (hexokinase), or potential for glycogenolysis (phosphorylase) and glycolysis (pyruvate kinase, phosphofructokinase, alpha-glycerophosphate dehydrogenase, lactate dehydrogenase). With the exception of increases in the capillary-to-fiber area ratio in type IIa fibers, no change was found in any fiber type (types I, IIa, and IIb) for area, number of capillaries, capillary-to-fiber area ratio, or oxidative potential with training.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardiovascular adaptations to exercise training in the elderly

Maximal O2 uptake (VO2max) and left ventricular function decrease with age. Endurance exercise training of sufficient intensity, frequency, and duration increases VO2max in the elderly. The mechanisms underlying the increased VO2max in the elderly are enhanced O2 extraction of trained muscle during maximal exercise leading to a wider arteriovenous O2 difference, and higher cardiac output in the trained state. However, increased cardiac output during true maximal exercise has not been documented in elderly subjects. Endurance exercise training results in a lower heart rate and rate pressure product during submaximal exercise at a given intensity. However, no improvement in left ventricular function has been reported in the elderly after exercise training. Highly trained master athletes exhibit proportional increases in the left ventricular end-diastolic dimension and wall thickness suggestive of volume-overload hypertrophy compared with age-matched sedentary controls. The magnitude of left ventricular enlargement is similar to that in young athletes. The failure of exercise training to alter the age-related deterioration of left ventricular function in the elderly may reflect an insufficient training stimulus rather than the inability of the heart to adapt to training in elderly subjects.     

Postural specificity of cardiovascular adaptations to exercise training

The purposes of this study were to determine 1) whether posture affects the magnitude of cardiovascular adaptations to training and 2) whether cardiovascular adaptations resulting from exercise training in the supine posture transfer (generalize) to exercise in the upright posture and vice versa. Sixteen sedentary men, aged 18-33 yr, were trained using high-intensity interval and prolonged continuous cycling in the supine (STG; supine training group) or upright (UTG; upright training group) posture 4 days/wk, 40 min/day, for 8 wk, while seven male subjects served as nontraining controls. After training, maximal O2 uptake measured during supine and upright cycling, respectively, increased significantly (P less than 0.05) by 22.9 and 16.1% in the STG and by 6.0 and 14.6% in the UTG. No significant cardiovascular adaptations were observed at rest. During submaximal supine cycling at 100 W, significant increases in end-diastolic volume (21%) and stroke volume (22%) (radionuclide ventriculography and CO2 rebreathing) and decreases in heart rate, blood pressure, and systemic vascular resistance occurred in the STG, whereas only a significant decrease in blood pressure occurred in the UTG. During upright cycling at 100 W, a significant decrease in blood pressure occurred in the STG, whereas significant increases in end-diastolic volume (17%) and stroke volume (18%) and decreases in blood pressure and systemic vascular resistance occurred in the UTG. Volume of myocardial contractility, ejection fraction, and systolic blood pressure-to-end-systolic volume ratio did not change significantly after training when measured during supine and upright cycling in either training group. Blood volume increased significantly in the UTG but remained unchanged in the STG.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma metabolic profile in COPD patients: effects of exercise and endurance training

The study examines plasma metabolic profiles of patients with chronic obstructive pulmonary disease (COPD) to prove whether the disease influences metabolism at rest and after endurance training. This is based on the hypothesis that metabolome levels should reflect impaired skeletal muscle bioenergetics in COPD. The study aims to test this hypothesis by evaluating plasma metabolic profiles in COPD patients before and after 8?weeks of endurance exercise training. We studied blood samples from 18 COPD patients and 12 healthy subjects. Pre- and post-training blood plasma samples at rest and after constant-work rate exercise (CWRE) at 70% of pre-training Watts peak were analyzed by ¹H-nuclear magnetic resonance spectroscopy to assess metabolite profiles. The two groups presented training-induced physiological changes in the VO₂ peak and in blood lactate levels (P?<?0.01 each). Before training, the two groups also showed differences in metabolic profiles at rest (P?<?0.05). Levels of valine (r?=?0.51, P?<?0.01), alanine (r?=?0.45, P?<?0.05) and isoleucine (r?=?0.51, P?<?0.01) were positively associated with body composition (Fat Free Mass Index). While training showed a significant impact on the metabolic profile in healthy subjects (P?<?0.001), with changes in levels of amino acids, creatine, succinate, pyruvate, glucose and lactate (P?<?0.05 each), no equivalent training-induced effects were seen in COPD patients in whom only lactate decreased (P?<?0.05). This study shows that plasma metabolic profiling contributes to the phenotypic characterization of COPD patients.     

Cardiac adaptations to endurance training in rats with a chronic myocardial infarction

The hemodynamic response to maximal exercise was determined in sedentary and trained rats with a chronic myocardial infarction (MI) produced by coronary artery ligation and in rats that underwent sham operations (SHAM). Infarct size in the MI groups of rats comprised 28-29% of the total left ventricle and resulted in both metabolic and hemodynamic changes that suggested that these animals had moderate compensated heart failure. The training regimen used in the present study produced significant increases in maximal O2 uptake (VO2max) when expressed in absolute terms (ml/min) or when normalized for body weight (ml.min-1.kg-1) and consisted of treadmill running at work loads that were equivalent to 70-80% of the animal's VO2max for a period of 60 min/day, 5 days/wk over an 8- to 10-wk interval. This training paradigm produced two major cardiocirculatory adaptations in the MI rat that had not been elicited previously when using a training paradigm of a lower intensity. First, the decrement in the maximal heart rate response to exercise (known as "chronotropic incompetence") found in the sedentary MI rat was completely reversed by endurance training. Second, the downregulation of cardiac myosin isozyme composition from the fast ATPase V1 isoform toward the slower ATPase (V2 and V3) isoforms in the MI rat was partially reversed by endurance training. These cardiac adaptations occurred without a significant increase in left ventricular pump function as an increase in maximal cardiac output (Qmax) and maximal stroke volume (SVmax) did not occur in the trained MI rat.(ABSTRACT TRUNCATED AT 250 WORDS)     

Muscle morphological and strength adaptations to endurance vs. resistance training

Fascicle angle (FA) is suggested to increase as a result of fiber hypertrophy and furthermore to serve as the explanatory link in the discrepancy in the relative adaptations in the anatomical cross-sectional area (CSA) and fiber CSA after resistance training (RT). In contrast to RT, the effects of endurance training on FA are unclear. The purpose of this study was therefore to investigate and compare the longitudinal effects of either progressive endurance training (END, n = 7) or RT (n = 7) in young untrained men on FA, anatomical CSA, and fiber CSA. Muscle morphological measures included the assessment of vastus lateralis FA obtained by ultrasonography and anatomical CSA by magnetic resonance imaging of the thigh and fiber CSA deduced from histochemical analyses of biopsy samples from m. vastus lateralis. Functional performance measures included VO2max and maximal voluntary contraction (MVC). The RT produced increases in FA by 23 ± 8% (p < 0.01), anatomical CSA of the knee extensor muscles by 9 ± 3% (p = 0.001), and fiber CSA by 19 ± 7% (p < 0.05). RT increased knee extensor MVC by 20 ± 5% (p < 0.001). END increased VO2max by 10 ± 2% but did not evoke changes in FA, anatomical CSA, or in fiber CSA. In conclusion, the morphological changes induced by 10 weeks of RT support that FA does indeed serve as the explanatory link in the observed discrepancy between the changes in anatomical and fiber CSA. Contrarily, 10 weeks of endurance training did not induce changes in FA, but the lack of morphological changes from END indirectly support the fact that fiber hypertrophy and FA are interrelated.     

Skeletal muscle biochemical adaptations to exercise training in miniature swine

McAllister, Richard M., Brian L. Reiter, John F. Amann, andM. Harold Laughlin. Skeletal muscle biochemical adaptations toexercise training in miniature swine. J. Appl.Physiol. 82(6): 1862-1868, 1997.The primarypurpose of this study was to test the hypothesis that enduranceexercise training induces increased oxidative capacity in porcineskeletal muscle. To test this hypothesis, female miniature swine wereeither trained by treadmill running 5 days/wk over 16-20 wk (Trn;n = 35) or pen confined (Sed;n = 33). Myocardialhypertrophy, lower heart rates during submaximal stages of a maximaltreadmill running test, and increased running time to exhaustion duringthat test were indicative of training efficacy. A variety of skeletalmuscles were sampled and subsequently assayed for the enzymes citratesynthase (CS), 3-hydroxyacyl-CoA dehydrogenase, and lactatedehydrogenase and for antioxidant enzymes. Fiber type composition of arepresentative muscle was also determined histochemically. The largestincrease in CS activity (62%) was found in the gluteus maximus muscle(Sed, 14.7 ± 1.1 µmol · min¹ · g¹;Trn, 23.9 ± 1.0; P < 0.0005).Muscles exhibiting increased CS activity, however, were locatedprimarily in the forelimb; ankle and knee extensor and respiratorymuscles were unchanged with training. Only two muscles exhibited higher3-hydroxyacyl-CoA dehydrogenase activity in Trn compared with Sed.Lactate dehydrogenase activity was unchanged with training, as wereactivities of antioxidant enzymes. Histochemical analysis of thetriceps brachii muscle (long head) revealed lower type IIB fibernumbers in Trn (Sed, 42 ± 6%; Trn, 10 ± 4;P < 0.01) and greater type IID/Xfiber numbers (Sed, 11 ± 2; Trn, 22 ± 3;P < 0.025). These findingsindicate that porcine skeletal muscle adapts to endurance exercisetraining in a manner similar to muscle of humans and other animalmodels, with increased oxidative capacity. Specificmuscles exhibiting these adaptations, however, differ between theminiature swine and other species.

     

Hepatic adaptations to iron deficiency and exercise training.

Brooks et al. [Am. J. Physiol. 253 (Endocrinol. Metab. 16): E461-E466, 1987] demonstrated an elevated gluconeogenic rate in resting iron-deficient rats. Because physical exercise also imposes demand on this hepatic function, we hypothesized that exercise training superimposed on iron deficiency would augment the hepatic capacity for amino acid transamination/deamination and pyruvate carboxylation. Sprague-Dawley rats (n = 32) were obtained at weaning (21 days of age) and randomly assigned to iron-sufficient (dietary iron = 60 mg iron/kg diet) or iron-deficient (3 mg iron/kg) dietary groups. Dietary groups were subdivided into sedentary and trained subgroups. Treadmill training was 4 wk in duration, 6 days/wk, 1 h/day, 0% grade. Treadmill speed was initially 26.8 m/min and was decreased to 14.3 m/min over the 4-wk training period. The mild exercise-training regimen did not affect any measured variable in iron-sufficient rats. In contrast, in iron-deficient animals, training increased endurance capacity threefold and reduced blood lactate and the lactate-to-alanine ratio during submaximal exercise by 34 and 27%, respectively. The mitochondrial oxidative capacity of gastrocnemius muscle was increased 46% by training. However, the oxidative capacity of liver was not affected by either iron deficiency or training. Maximal rates of pyruvate carboxylation and glutamine metabolism by isolated liver mitochondria were also evaluated. Iron deficiency and training interacted to increase pyruvate carboxylation by intact mitochondria. Glutamine metabolism was increased roughly threefold by iron deficiency alone, and training amplified this effect to a ninefold increase over iron-sufficient animals.(ABSTRACT TRUNCATED AT 250 WORDS)     

Large energetic adaptations of elderly muscle to resistance and endurance training.

This study determined the cellular energetic and structural adaptations of elderly muscle to exercise training. Forty male and female subjects (69.2 +/- 0.6 yr) were assigned to a control group or 6 mo of endurance (ET) or resistance training (RT). We used magnetic resonance spectroscopy and imaging to characterize energetic properties and size of the quadriceps femoris muscle. The phosphocreatine and pH changes during exercise yielded the muscle oxidative properties, glycolytic ATP synthesis, and contractile ATP demand. Muscle biopsies taken from the same site as the magnetic resonance measurements were used to determine myosin heavy chain isoforms, metabolite concentrations, and mitochondrial volume densities. The ET group showed changes in all energetic pathways: oxidative capacity (+31%), contractile ATP demand (-21%), and glycolytic ATP supply (-56%). The RT group had a large increase in oxidative capacity (57%). Only the RT group exhibited change in structural properties: a rise in mitochondrial volume density (31%) and muscle size (10%). These results demonstrate large energetic, but smaller structural, adaptations by elderly muscle with exercise training. The rise in oxidative properties with both ET and RT suggests that the aerobic pathway is particularly sensitive to exercise training in elderly muscle. Thus elderly muscle remains adaptable to chronic exercise, with large energetic changes accompanying both ET and RT.     

Skeletal muscle metabolic and ionic adaptations during intense exercise following sprint training in humans.

The effects of sprint training on muscle metabolism and ion regulation during intense exercise remain controversial. We employed a rigorous methodological approach, contrasting these responses during exercise to exhaustion and during identical work before and after training. Seven untrained men undertook 7 wk of sprint training. Subjects cycled to exhaustion at 130% pretraining peak oxygen uptake before (PreExh) and after training (PostExh), as well as performing another posttraining test identical to PreExh (PostMatch). Biopsies were taken at rest and immediately postexercise. After training in PostMatch, muscle and plasma lactate (Lac(-)) and H(+) concentrations, anaerobic ATP production rate, glycogen and ATP degradation, IMP accumulation, and peak plasma K(+) and norepinephrine concentrations were reduced (P<0.05). In PostExh, time to exhaustion was 21% greater than PreExh (P<0.001); however, muscle Lac(-) accumulation was unchanged; muscle H(+) concentration, ATP degradation, IMP accumulation, and anaerobic ATP production rate were reduced; and plasma Lac(-), norepinephrine, and H(+) concentrations were higher (P<0.05). Sprint training resulted in reduced anaerobic ATP generation during intense exercise, suggesting that aerobic metabolism was enhanced, which may allow increased time to fatigue.     

Metformin inhibits mitochondrial adaptations to aerobic exercise training in older adults

Metformin and exercise independently improve insulin sensitivity and decrease the risk of diabetes. Metformin was also recently proposed as a potential therapy to slow aging. However, recent evidence indicates that adding metformin to exercise antagonizes the exercise‐induced improvement in insulin sensitivity and cardiorespiratory fitness. The purpose of this study was to test the hypothesis that metformin diminishes the improvement in insulin sensitivity and cardiorespiratory fitness after aerobic exercise training (AET) by inhibiting skeletal muscle mitochondrial respiration and protein synthesis in older adults (62 ± 1 years). In a double‐blinded fashion, participants were randomized to placebo (n = 26) or metformin (n = 27) treatment during 12 weeks of AET. Independent of treatment, AET decreased fat mass, HbA1c, fasting plasma insulin, 24‐hr ambulant mean glucose, and glycemic variability. However, metformin attenuated the increase in whole‐body insulin sensitivity and VO₂max after AET. In the metformin group, there was no overall change in whole‐body insulin sensitivity after AET due to positive and negative responders. Metformin also abrogated the exercise‐mediated increase in skeletal muscle mitochondrial respiration. The change in whole‐body insulin sensitivity was correlated to the change in mitochondrial respiration. Mitochondrial protein synthesis rates assessed during AET were not different between treatments. The influence of metformin on AET‐induced improvements in physiological function was highly variable and associated with the effect of metformin on the mitochondria. These data suggest that prior to prescribing metformin to slow aging, additional studies are needed to understand the mechanisms that elicit positive and negative responses to metformin with and without exercise.     

Conserved multi-tissue transcriptomic adaptations to exercise training in humans and mice

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Molecular adaptations in human skeletal muscle to endurance training under simulated hypoxic conditions.

This study was performed to explore changes in gene expression as a consequence of exercise training at two levels of intensity under normoxic and normobaric hypoxic conditions (corresponding to an altitude of 3,850 m). Four groups of human subjects trained five times a week for a total of 6 wk on a bicycle ergometer. Muscle biopsies were taken, and performance tests were carried out before and after the training period. Similar increases in maximal O(2) uptake (8.3-13.1%) and maximal power output (11.4-20.8%) were found in all groups. RT-PCR revealed elevated mRNA concentrations of the alpha-subunit of hypoxia-inducible factor 1 (HIF-1) after both high- (+82.4%) and low (+78.4%)-intensity training under hypoxic conditions. The mRNA of HIF-1alpha(736), a splice variant of HIF-1alpha newly detected in human skeletal muscle, was shown to be changed in a similar pattern as HIF-1alpha. Increased mRNA contents of myoglobin (+72.2%) and vascular endothelial growth factor (+52.4%) were evoked only after high-intensity training in hypoxia. Augmented mRNA levels of oxidative enzymes, phosphofructokinase, and heat shock protein 70 were found after high-intensity training under both hypoxic and normoxic conditions. Our findings suggest that HIF-1 is specifically involved in the regulation of muscle adaptations after hypoxia training. Fine-tuning of the training response is recognized at the molecular level, and with less sensitivity also at the structural level, but not at global functional responses like maximal O(2) uptake or maximal power output.     

Ventilatory chemosensitive adaptations to intermittent hypoxic exposure with endurance training and detraining.

The present study was performed to clarify the effects of intermittent exposure to an altitude of 4,500 m with endurance training and detraining on ventilatory chemosensitivity. Seven subjects (sea-level group) trained at sea level at 70% maximal oxygen uptake (VO2 max) for 30 min/day, 5 days/wk for 2 wk, whereas the other seven subjects (altitude group) trained at the same relative intensity (70% altitude VO2 max) in a hypobaric chamber. VO2 max, hypoxic ventilatory response (HVR), and hypercapnic ventilatory response, as an index of central hypercapnic chemosensitivity (HCVR) and as an index of peripheral chemosensitivity (HCVRSB), were measured. In both groups VO2 max increased significantly after training, and a significant loss of VO2 max occurred during 2 wk of detraining. HVR tended to increase in the altitude group but not significantly, whereas it decreased significantly in the sea-level group after training. HCVR and HCVRSB did not change in each group. After detraining, HVR returned to the pretraining level in both groups. These results suggest that ventilatory chemosensitivity to hypoxia is more variable by endurance training and detraining than that to hypercapnia.     

Effect of endurance training on excessive CO2 expiration due to lactate production in exercise

We attempted to determine the change in total excess volume of CO2 output (CO2 excess) due to bicarbonate buffering of lactic acid produced in exercise due to endurance training for approximately 2 months and to assess the relationship between the changes of CO2 excess and distance-running performance. Six male endurance runners, aged 19-22 years, were subjects. Maximal oxygen uptake (VO2max), oxygen uptake (VO2) at anaerobic threshold (AT), CO2 excess and blood lactate concentration were measured during incremental exercise on a cycle ergometer and 12-min exhausting running performance (12-min ERP) was also measured on the track before and after endurance training. The absolute magnitudes in the improvement due to training for CO2 excess per unit of body mass per unit of blood lactate accumulation (delta la-) in exercise (CO2 excess.mass-1.delta la-), 12-min ERP, VO2 at AT (AT-VO2) and VO2max on average were 0.8 ml.kg-1.l-1.mmol-1, 97.8 m, 4.4 ml.kg-1. min-1 and 7.3 ml.kg-1.min-1, respectively. The percentage change in CO2 excess.mass-1.delta la- (15.7%) was almost same as those of VO2max (13.7%) and AT-VO2 (13.2%). It was found to be a high correlation between the absolute amount of change in CO2 excess.mass-1.delta la-, and the absolute amount of change in AT-VO2 (r = 0.94, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)