Central regulation of skeletal muscle recruitment explains the reduced maximal cardiac output during exercise in hypoxia.
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Acute Disease↗
Biomedical subjects
Bengt Saltin
Publications and source records attributed to Bengt Saltin.
Does the aging skeletal muscle maintain its endocrine function?
Contracting skeletal muscles produce and release the cytokine interleukin (IL)-6 and this release is augmented by the presence of low muscle glycogen. Since muscle metabolism in elderly subjects relies on glycogen more than younger subjects, it is possible that aging is associated with an altered production of muscle-derived IL-6 during exercise. To test the relation between aging and muscle-derived IL-6, seven healthy elderly males, mean age 70+/-1 (SEM) yr and six healthy young males, mean age 26+/-2 (SEM) yr performed three hours of dynamic knee-extensor exercise at 50% of maximal work load (Wmax). IL-6 mRNA and glycogen in muscles were analysed and the IL-6 release were estimated before, during and after the exercise. Although the absolute work load in the elderly was less than half of that in the young, 41.1+/-3.1 W and 92.5+/-4.0 W, respectively, the muscle glycogen utilization after three hours of exercise did not differ between groups, 238.7+/-52.4 and 245.2+/-74.0 mmol/kg muscle in elderly and young, respectively. This could explain that the IL-6 release and the IL-6 mRNA amplification increased during exercise with no difference between groups, two-way ANOVA-P = 0.50 and 0.45, respectively. In conclusion, elderly healthy people maintain the capacity to produce and release IL-6 in response to dynamic exercise, with no difference compared to young individuals furthermore, glycogen utilization expressed in changes of glycogen related to muscle mass was equal in elderly and young subject at 50 % of Wmax.
Adult↗
The effect of ageing and immobilization on structure and function of human skeletal muscle fibres.
Biopsy samples were taken from vastus lateralis muscle of seven young (YO, age 30.2 +/- 2.2 years), and seven elderly (EL, age 72.7 +/- 2.3 years) subjects and two elderly subjects whose right leg had been immobilized for 3.5 months (EL-IMM, ages 70 and 75). The following main parameters were studied: (1) myosin heavy chain (MHC) isoform distribution of the samples, determined by SDS-PAGE; (2) cross-sectional area (CSA), specific force (Po/CSA) and maximum shortening velocity (Vo) of a large population (n = 593) of single skinned muscle fibres, classified on the basis of MHC isoform composition determined by SDS-PAGE; (3) actin sliding velocity (Vf) on pure myosin isoforms determined by in vitro motility assays; (4) myosin concentration in single fibres determined by quantitative SDS-PAGE. MHC isoform distribution was shifted towards fast isoforms in EL and to a larger extent in EL-IMM. In EL and, more consistently, in EL-IMM we observed a higher percentage of hybrid fibres than in YO, and noted the presence of MHC-neonatal and of unusual hybrid fibres containing more than two MHC isoforms. Po/CSA significantly decreased in type 1 and 2A fibres in the order YO EL EL-IMM. Vo of type 1 and 2A fibres was significantly lower in EL and higher in EL-IMM than in YO, i.e. immobilization more than counteracted the age-dependent decrease in Vo. The latter phenomenon was not observed for Vf. Vf on myosin 1 was lower in both EL and EL-IMM than in YO. Vf on myosin 2X was lower in EL than in YO, and a similar trend was observed for myosin 2A. Myosin concentration decreased in type 1 and 2A fibres in the order YO EL EL-IMM and was linearly related to the Po/CSA values of corresponding fibre types from the same subjects. The experiments suggest that (1) myosin concentration is a major determinant of the lower Po/CSA of single fibres in ageing and especially following immobilization and (2) ageing is associated with lower Vo of single fibres due to changes in the properties of myosin itself, whereas immobilization is associated with higher Vo in the absence of a change in myosin function.
Adult↗
Glucose ingestion blunts hormone-sensitive lipase activity in contracting human skeletal muscle.
To examine the effect of attenuated epinephrine and elevated insulin on intramuscular hormone sensitivity lipase activity (HSLa) during exercise, seven men performed 120 min of semirecumbent cycling (60% peak pulmonary oxygen uptake) on two occasions while ingesting either 250 ml of a 6.4% carbohydrate (GLU) or sweet placebo (CON) beverage at the onset of, and at 15 min intervals throughout, exercise. Muscle biopsies obtained before and immediately after exercise were analyzed for HSLa. Blood samples were simultaneously obtained from a brachial artery and a femoral vein before and during exercise, and leg blood flow was measured by thermodilution in the femoral vein. Net leg glycerol and lactate release and net leg glucose and free fatty acid (FFA) uptake were calculated from these measures. Insulin and epinephrine were also measured in arterial blood before and throughout exercise. During GLU, insulin was elevated (120 min: CON, 11.4 +/- 2.4, GLU, 35.3 +/- 6.9 pM, P < 0.05) and epinephrine suppressed (120 min: CON, 6.1 +/- 2.5, GLU, 2.1 +/- 0.9 nM; P < 0.05) compared with CON. Carbohydrate feeding also resulted in suppressed (P < 0.05) HSLa relative to CON (120 min: CON, 1.71 +/- 0.18, GLU, 1.27 +/- 0.16 mmol.min-1.kg dry mass-1). There were no differences in leg lactate or glycerol release when trials were compared, but leg FFA uptake was lower (120 min: CON, 0.29 +/- 0.06, GLU, 0.82 +/- 0.09 mmol/min) and leg glucose uptake higher (120 min: CON, 3.16 +/- 0.59, GLU, 1.37 +/- 0.37 mmol/min) in GLU compared with CON. These results demonstrate that circulating insulin and epinephrine play a role in HSLa in contracting skeletal muscle.
Carbohydrate Metabolism↗
Exercise induces transient transcriptional activation of the PGC-1alpha gene in human skeletal muscle.
Endurance exercise training induces mitochondrial biogenesis in skeletal muscle. The peroxisome proliferator activated receptor co-activator 1alpha (PGC-1alpha) has recently been identified as a nuclear factor critical for coordinating the activation of genes required for mitochondrial biogenesis in cell culture and rodent skeletal muscle. To determine whether PGC-1alpha transcription is regulated by acute exercise and exercise training in human skeletal muscle, seven male subjects performed 4 weeks of one-legged knee extensor exercise training. At the end of training, subjects completed 3 h of two-legged knee extensor exercise. Biopsies were obtained from the vastus lateralis muscle of both the untrained and trained legs before exercise and after 0, 2, 6 and 24 h of recovery. Time to exhaustion (2 min maximum resistance), as well as hexokinase II (HKII), citrate synthase and 3-hydroxyacyl-CoA dehydrogenase mRNA, were higher in the trained than the untrained leg prior to exercise. Exercise induced a marked transient increase (P < 0.05) in PGC-1alpha transcription (10- to > 40-fold) and mRNA content (7- to 10-fold), peaking within 2 h after exercise. Activation of PGC-1alpha was greater in the trained leg despite the lower relative workload. Interestingly, exercise did not affect nuclear respiratory factor 1 (NRF-1) mRNA, a gene induced by PGC-1alpha in cell culture. HKII, mitochondrial transcription factor A, peroxisome proliferator activated receptor alpha, and calcineurin Aalpha and Abeta mRNA were elevated (approximately 2- to 6-fold; P < 0.05) at 6 h of recovery in the untrained leg but did not change in the trained leg. The present data demonstrate that exercise induces a dramatic transient increase in PGC-1alpha transcription and mRNA content in human skeletal muscle. Consistent with its role as a transcriptional coactivator, these findings suggest that PGC-1alpha may coordinate the activation of metabolic genes in human muscle in response to exercise.
3-Hydroxyacyl CoA Dehydrogenases↗
Cytochrome P450 2C9 plays an important role in the regulation of exercise-induced skeletal muscle blood flow and oxygen uptake in humans.
Previous studies show that exercise-induced hyperaemia is unaffected by systemic inhibition of nitric oxide synthase (NOS) and it has been proposed that this may be due to compensation by other vasodilators. We studied the involvement of cytochrome P450 2C9 (CYP 2C9) in the regulation of skeletal muscle blood flow in humans and the interaction between CYP 2C9 and NOS. Seven males performed knee extensor exercise. Blood flow was measured by thermodilution and blood samples were drawn frequently from the femoral artery and vein at rest, during exercise and in recovery. The protocol was repeated three times on the same day. The first and the third protocols were controls, and in the second protocol either the CYP 2C9 inhibitor sulfaphenazole alone, or sulfaphenazole in combination with the NOS inhibitor N(omega)-monomethyl-L-arginine (L-NMMA) were infused. Compared with control there was no difference in blood flow at any time with sulfaphenazole infusion (P > 0.05) whereas with infusion of sulfaphenazole and L-NMMA, blood flow during exercise was 16 +/- 4 % lower than in control (9 min: 3.67 +/- 0.31 vs. 4.29 +/- 0.20 l min(-1); P < 0.05). Oxygen uptake during exercise was 12 +/- 3 % lower (9 min: 525 +/- 46 vs. 594 +/- 24 ml min(-1); P < 0.05) with co-infusion of sulfaphenazole and L-NMMA, whereas oxygen uptake during sulfaphenazole infusion alone was not different from that of control (P > 0.05). The results demonstrate that CYP 2C9 plays an important role in the regulation of hyperaemia and oxygen uptake during exercise. Since inhibition of neither NOS nor CYP 2C9 alone affect skeletal muscle blood flow, an interaction between CYP 2C9 and NOS appears to exist so that a CYP-dependent vasodilator mechanism takes over when NO production is compromised.
Adult↗
Interleukin-6 stimulates lipolysis and fat oxidation in humans.
Although IL-6 is a key modulator of immune function, it also plays a role in regulating substrate metabolism. To determine whether IL-6 affects lipid metabolism, 18 healthy men were infused for 3 h with saline (Con; n = 6) or a high dose (High-rhIL6; n = 6) or a low dose (Low-rhIL6; n = 6) of recombinant human IL-6 (rhIL-6). The IL-6 concentration during Con, Low-rhIL6, and High-rhIL6 was at a steady state after 30 min of infusion at approximately 4, 140, and 320 pg/ml, respectively. Either dose of rhIL-6 was associated with a similar increase in fatty acid (FA) concentration and endogenous FA rate of appearance (R(a)) from 90 min after the start of the infusion. The FA concentration and FA R(a) continued to increase until the cessation of rhIL-6 infusion, reaching levels approximately 50% greater than Con values. The elevated levels reached at the end of rhIL-6 infusion persisted at least 3 h postinfusion. Triacylglycerol concentrations were unchanged during rhIL-6 infusion, whereas whole body fat oxidation increased after the second hour of rhIL-6 infusion. Of note, during Low-rhIL6, the induced elevation in FA concentration and FA R(a) occurred in the absence of any change in adrenaline, insulin, or glucagon, and no adverse side effects were observed. In conclusion, the data identify IL-6 as a potent modulator of fat metabolism in humans, increasing fat oxidation and FA reesterification without causing hypertriacylglyceridemia.
Adult↗
Skiing across the Greenland icecap: divergent effects on limb muscle adaptations and substrate oxidation.
This study investigates the adaptive response of the lower limb muscles and substrate oxidation during submaximal arm or leg exercise after a crossing of the Greenland icecap on cross-country skies. Before and after the 42-day expedition, four male subjects performed cycle ergometer and arm-cranking exercise on two separate days. On each occasion, the subjects exercised at two submaximal loads (arm exercise, 45 W and 100 W; leg exercise, 100 W and 200 W). In addition, peak oxygen uptake ((VO(2max))) was determined for both leg and arm exercise. Before and after the crossing, a muscle biopsy was obtained from the vastus lateralis and the triceps brachii muscles prior to exercise (N=3). After the crossing, body mass decreased by 5.7+/-0.5 kg (in four of four subjects), whereas (VO(2max)) was unchanged in the arm (3.1+/-0.2 l min(-1)) and leg (4.0+/-0.1 l min(-1)). Before the crossing, respiratory exchange ratio (RER) values were 0.84+/-0.02 and 0.96+/-0.02 during submaximal arm exercise and 0.82+/-0.02 and 0.91+/-0.01 during submaximal leg exercise at the low and high workloads, respectively. After the crossing, RER was lower (in three of four subjects) during arm exercise (0.74+/-0.02 and 0.81+/-0.01) but was higher (in three of four subjects) during leg exercise (0.92+/-0.02 and 0.96+/-0.01) at the low and high workloads, respectively. Citrate synthase and beta-hydroxy-acyl-CoA-dehydrogenase activity was decreased by approximately 29% in vastus lateralis muscle and was unchanged in triceps brachii muscle. Fat oxidation during submaximal arm exercise was enhanced without a concomitant increase in the oxidative capacity of the triceps brachii muscle after the crossing. This contrasted with decreased fat oxidation during leg exercise, which occurred parallel to a decreased oxidative capacity in vastus lateralis muscle. Although the number of subjects is limited, these results imply that the adaptation pattern after long-term, prolonged, low-intensity, whole body exercise may vary dramatically among muscles.
Adaptation, Physiological↗
Effect of short-term fasting and refeeding on transcriptional regulation of metabolic genes in human skeletal muscle.
During short-term fasting, substrate utilization in skeletal muscle shifts from predominantly carbohydrate to fat as a means of conserving glucose. To examine the potential influence of short-term fasting and refeeding on transcriptional regulation in skeletal muscle, muscle biopsies were obtained from nine male subjects at rest, after 20 h of fasting, and 1 h after consuming either a high-carbohydrate (CHO trial) or a low-carbohydrate (FAT trial) meal. Fasting induced an increase in transcription of the pyruvate dehydrogenase kinase 4 (PDK4) (10-fold), lipoprotein lipase (LPL) ( approximately 2-fold), uncoupling protein 3 (UCP3) ( approximately 5-fold), and carnitine palmitoyltransferase I (CPT I) ( approximately 2.5-fold) genes. Surprisingly, transcription of PDK4 and LPL increased further in response to refeeding (both trials) to more than 50-fold and 6- to 10-fold, respectively, over prefasting levels. However, responses varied among subjects with two subjects in particular displaying far greater activation of PDK4 (>100-fold) and LPL (>20-fold) than the other subjects (mean approximately 8-fold and approximately 2-fold, respectively). Transcription of UCP3 decreased to basal levels after the CHO meal but remained elevated after the FAT meal, whereas CPT I remained elevated after both refeeding meals. The present findings demonstrate that short-term fasting/refeeding in humans alters the transcription of several genes in skeletal muscle related to lipid metabolism. Marked heterogeneity in the transcriptional response to the fasting/refeeding protocol suggests that individual differences in genetic profile may play an important role in adaptive molecular responses to metabolic challenges.
Adult↗
Dissociation between muscle tricarboxylic acid cycle pool size and aerobic energy provision during prolonged exercise in humans.
It has been suggested that a decrease in the total concentration of tricarboxylic acid cycle intermediates (TCAIs)--secondary to a reduction in glycogen availability--compromises oxidative energy provision in skeletal muscle during prolonged exercise. However, no study has directly tested this hypothesis. We therefore studied six men (28 +/- 2 years) during 90 min of leg kicking exercise at an intensity equivalent to 70 % of maximum. Biopsies (vastus lateralis) were obtained at rest and after 5, 10, 15, 30, 60 and 90 min of exercise, and thigh oxygen uptake (V(O(2),thigh)) was calculated according to the Fick principle. The sum of six measured TCAIs (approximately 95 % of total pool size) was 1.30 +/- 0.15 mmol (kg dry wt)(-1) at rest and increased (P < or = 0.05) rapidly during exercise to a peak value of 3.15 +/- 0.23 mmol (kg dry wt)(-1) after 10 min. Thereafter, the [TCAI] declined to 2.14 +/- 0.23, 1.73 +/- 0.32 and 1.62 +/- 0.10 mmol (kg dry wt)(-1) after 30, 60 and 90 min, respectively (P < or = 0.05 vs.10 min). Despite the 50 % decrease in [TCAI], aerobic energy provision was not compromised, as evidenced by stable V(O(2),thigh) values throughout the entire exercise bout and little change in muscle [phosphocreatine] after 10 min. The largest decrease in [TCAI] (delta = 1.00 +/- 0.24 mmol (kg dry wt)(-1)) occurred from 10 to 30 min of exercise despite the fact that muscle [glycogen] remained relatively high at this point in exercise (approximately 274 +/- 24 mmol (kg dry wt)(-1) after 30 min; approximately 65 % of rest value). Conversely, there was little change in [TCAI] during the final 30 min of exercise (delta = 0.11 +/- 0.29 mmol (kg dry wt)(-1)) despite a decrease in [glycogen] to approximately 72 +/- 3 mmol (kg dry wt)(-1) after 90 min (approximately 13 % of rest value). We conclude that there is a progressive decrease in muscle [TCAI] during prolonged exercise in humans; however this decrease does not compromise aerobic energy provision and is not attributable to the depletion of muscle [glycogen].
Adult↗
Erythrocyte and the regulation of human skeletal muscle blood flow and oxygen delivery: role of circulating ATP.
Blood flow to contracting skeletal muscle is tightly coupled to the oxygenation state of hemoglobin. To investigate if ATP could be a signal by which the erythrocyte contributes to the regulation of skeletal muscle blood flow and oxygen (O2) delivery, we measured circulating ATP in 8 young subjects during incremental one-legged knee-extensor exercise under conditions of normoxia, hypoxia, hyperoxia, and CO+normoxia, which produced reciprocal alterations in arterial O2 content and thigh blood flow (TBF), but equal thigh O2 delivery and thigh O2 uptake. With increasing exercise intensity, TBF, thigh vascular conductance (TVC), and femoral venous plasma [ATP] augmented significantly (P<0.05) in all conditions. However, with hypoxia, TBF, TVC, and femoral venous plasma [ATP] were (P<0.05) or tended (P=0.14) to be elevated compared with normoxia, whereas with hyperoxia they tended to be reduced. In CO+normoxia, where femoral venous O2Hb and (O2+CO)Hb were augmented compared with hypoxia despite equal arterial deoxygenation, TBF and TVC were elevated, whereas venous [ATP] was markedly reduced. At peak exercise, venous [ATP] in exercising and nonexercising limbs was tightly correlated to alterations in venous (O2+CO)Hb (r2=0.93 to 0.96; P<0.01). Intrafemoral artery infusion of ATP at rest in normoxia (n=5) evoked similar increases in TBF and TVC than those observed during exercise. Our results in humans support the hypothesis that the erythrocyte functions as an O2 sensor, contributing to the regulation of skeletal muscle blood flow and O2 delivery, by releasing ATP depending on the number of unoccupied O2 binding sites in the hemoglobin molecule.
Adenosine Triphosphate↗
Dissociation of AMPK activity and ACCbeta phosphorylation in human muscle during prolonged exercise.
During prolonged, low intensity exercise, the type of substrate utilized varies with time. If 5' AMP-activated protein kinase (AMPK) regulates muscle metabolism during exercise, signaling through AMPK would be expected to change in concordance with changes in substrate utilization. Six healthy, young males cycled (approximately 45% VO(2peak)) until exhaustion (approximately 3.5h). During exercise, leg glucose uptake and rate of glycogenolysis gradually decreased whereas free fatty acid uptake gradually increased. In the thigh muscle, the alpha AMPK subunits became progressively more phosphorylated on Thr(172) during exercise eliciting a parallel increase in alpha2 but not alpha1 AMPK activity. In contrast, after 1h of exercise, Ser(221) phosphorylation of acetyl-CoA carboxylase-beta (ACCbeta) peaked at 1h of exercise and returned to resting levels at exhaustion. Protein expression of alpha2 AMPK, alpha1 AMPK or ACCbeta did not change with time. These data suggest that AMPK signaling is not a key regulatory system of muscle substrate combustion during prolonged exercise and that marked activation of AMPK via phosphorylation is not sufficient to maintain an elevated ACCbeta Ser(221) phosphorylation during prolonged exercise.
AMP-Activated Protein Kinase Kinases↗
Muscle glycogen content and glucose uptake during exercise in humans: influence of prior exercise and dietary manipulation.
There are many factors that can influence glucose uptake by contracting skeletal muscle during exercise and although one may be intramuscular glycogen content, this relationship is at present not fully elucidated. To test the hypothesis that muscle glycogen concentration influences glucose uptake during exercise, 13 healthy men were studied during two series of experiments. Seven men completed 4 h of two-legged knee extensor exercise 16 h after reducing of muscle glycogen by completing 60 min of single-legged cycling (Series 1). A further six men completed 3 h of two-legged knee extensor exercise on two occasions: one after 60 min of two-legged cycling (16 h prior to the experimental trial) followed by a high carbohydrate diet (HCHO) and the other after the same exercise followed by a low carbohydrate diet (LCHO) (Series 2). Muscle glycogen was decreased by 40 % when comparing the pre-exercised leg (EL) with the control leg (CL) prior to exercise in Series 1. In addition, muscle glycogen was decreased by the same magnitude when comparing LCHO with HCHO in Series 2. In Series 1, glucose uptake was 3-fold higher in the first 60 min of exercise, in the presence of unchanged pre-exercise GLUT4 protein in EL compared with CL, suggesting that the lower glycogen, and not the exercise the day before, might have provided the stimulus for increased glucose uptake. Despite the same magnitude of difference in pre-exercise glycogen concentration when comparing Series 1 with Series 2, neither direct-nor isotopic tracer-determined glucose uptake was higher in LCHO compared with HCHO in Series 2. However, arterial concentrations of insulin and glucose were lower, while free fatty acids and adrenaline were higher in LCHO compared with HCHO. These data suggest that pre-exercise glycogen content may influence glucose uptake during subsequent exercise. However, this is only the case when delivery of substrates and hormones remains constant. When delivery of substrates and hormones is altered, the potential effect of glycogen on glucose uptake is negated.
Adult↗
Influence of pre-exercise muscle glycogen content on exercise-induced transcriptional regulation of metabolic genes.
Transcription of metabolic genes is transiently induced during recovery from exercise in skeletal muscle of humans. To determine whether pre-exercise muscle glycogen content influences the magnitude and/or duration of this adaptive response, six male subjects performed one-legged cycling exercise to lower muscle glycogen content in one leg and then, the following day, completed 2.5 h low intensity two-legged cycling exercise. Nuclei and mRNA were isolated from biopsies obtained from the vastus lateralis muscle of the control and reduced glycogen (pre-exercise glycogen = 609 +/- 47 and 337 +/- 33 mmol kg(-1) dry weight, respectively) legs before and after 0, 2 and 5 h of recovery. Exercise induced a significant (P < 0.05) increase (2- to 3-fold) in transcription of the pyruvate dehydrogenase kinase 4 (PDK4) and uncoupling protein 3 (UCP3) genes in the reduced glycogen leg only. Although PDK4, lipoprotein lipase (LPL) and hexokinase II (HKII) mRNA were elevated in the reduced glycogen leg before exercise, no consistent difference was found between the two legs in response to exercise. In a second study, six subjects completed two trials (separated by 2 weeks) consisting of 3 h of two-legged knee extensor exercise with either control (398 +/- 52 mmol kg(-1) dry weight) or low (240 +/- 38 mmol kg(-1) dry weight) pre-exercise muscle glycogen. Exercise induced a significantly greater increase in PDK4 transcription in the low glycogen (> 6-fold) than in the control (< 3-fold) trial. Induction of PDK4 and UCP3 mRNA in response to exercise was also significantly higher in the low glycogen (11.4- and 3.5-fold, respectively) than in the control (5.0- and 1.7-fold, respectively) trial. These data indicate that low muscle glycogen content enhances the transcriptional activation of some metabolic genes in response to exercise, raising the possibility that signalling mechanisms sensitive to glycogen content and/or FFA availability may be linked to the transcriptional control of exercise-responsive genes.
Adult↗
[Metabolic fitness: physical activity and health].
Physical inactivity is strongly associated with an increased risk of premature disease and death, and the falling level of physical activity in Denmark (as in many other countries) makes physical inactivity a major life-style risk factor in many western countries today. Both aerobic fitness (maximum oxygen uptake) and metabolic capacity of the muscles are important in this matter. The present paper focuses on the role of the metabolic capacity/fitness of muscle, because this appears to be especially critical for the development of metabolic-related diseases and thus for the health of the individual. A definition of metabolic fitness is proposed as the ratio between mitochondrial capacity for substrate utilisation and maximum oxygen uptake of the muscle. Indirect means of determining this parameter are discussed. Skeletal muscle is an extraordinarily plastic tissue and metabolic capacity/fitness changes quickly when the level of physical activity is altered. High metabolic fitness includes an elevated use of fat at rest and during exercise. The capacity for glucose metabolism is also enhanced in trained muscle. Some of these adaptations to physical activity are explained. Exercise-induced activation of genes coding for proteins involved in metabolism is described as an underlying mechanism for some of these adaptations. The increased gene expression is of relatively short duration, which implies that a certain regularity of physical activity is required to maintain high metabolic fitness. Thus, metabolic fitness is directly related to how much the muscle is used, but even low levels of physical activity have a beneficial effect on metabolic fitness and the overall health of the individual.
Exercise↗
Reduced glycogen availability is associated with an elevation in HSP72 in contracting human skeletal muscle.
To test the hypothesis that a decrease in intramuscular glycogen availability may stimulate heat shock protein expression, seven men depleted one leg of muscle glycogen the day before performing 4-5 h of exhaustive, two-legged knee extensor exercise at 40 % of leg peak power output. Subjects then rested for a further 3 h. Muscle biopsies were obtained from the depleted and control leg before, immediately after and 3 h into recovery from exercise. These samples were analysed for muscle glycogen, and HSP72 gene and protein expression. In addition, catheters were placed in one femoral artery and both femoral veins and blood was sampled from these catheters prior to exercise and at 1 h intervals during exercise and into recovery for the measurement of arterial-venous differences in serum HSP72. Plasma creatine kinase (CK) was also measured from arterial blood samples. Pre-exercise muscle glycogen content was 40 % lower in the depleted compared with the control leg and this difference was maintained throughout the experiment (P < 0.05; main treatment effect). Neither HSP72 gene nor protein expression was different pre-exercise. However, both HSP72 gene and protein increased (P < 0.05) post-exercise in the depleted leg, but not in the control leg. Exercise did not increase plasma CK concentrations and we were unable to detect HSP72 in the serum of any samples. These results demonstrate that while acute, concentric exercise is capable of increasing HSP72 in human skeletal muscle, it does so only when glycogen is reduced to relatively low levels. Hence, our data suggest that HSP72 protein expression is related to glycogen availability. In addition, because CK did not increase and we found no evidence of HSP72 in the venous effluent, our data suggest that skeletal muscle is impermeable to HSP72.
Adult↗
Comments on Brønnum-Hansen: predicting the effect of prevention of ischaemic heart disease.
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Comorbidity↗
Enhanced pyruvate dehydrogenase activity does not affect muscle O2 uptake at onset of intense exercise in humans.
It has been proposed that the activation state of pyruvate dehydrogenase (PDH) may influence the rate of skeletal muscle O2 uptake during the initial phase of exercise; however, this has not been directly tested in humans. To remedy this, we used dichloroacetate (DCA) infusion to increase the active form of PDH (PDH(a)) and, subsequently, measured leg O2 uptake and markers of anaerobic ATP provision during conditions of intense dynamic exercise, when the rate of muscle O2 uptake would be very high. Six subjects performed brief bouts of one-legged knee-extensor exercise at approximately 110% of thigh peak O2 uptake (65.3 +/- 3.7 W) on several occasions: under noninfused control (Con) and DCA-supplemented conditions. Needle biopsy samples from the vastus lateralis muscle were obtained at rest and after 5 s, 15 s, and 3 min of exercise during both experimental conditions. In addition, thigh blood flow and femoral arteriovenous differences for O2 and lactate were measured repeatedly during the 3-min work bouts (Con and DCA) to calculate thigh O2 uptake and lactate release. After DCA administration, PDH(a) was four- to eightfold higher (P < 0.05) than Con at rest, and PDH(a) remained approximately 130% and 100% higher (P < 0.05) after 5 and 15 s of exercise, respectively. There was no difference between trials after 3 min. Despite the marked difference in PDH(a) between trials at rest and during the initial phase of exercise, thigh O2 uptake was the same. In addition, muscle phosphocreatine utilization and lactate production were similar after 5 s, 15 s, and 3 min of exercise in DCA and Con. The present findings demonstrate that increasing PDH(a) does not alter muscle O2 uptake and anaerobic ATP provision during the initial phase of intense dynamic knee-extensor exercise in humans.
Adult↗