[To challenge a dogma--altitude research with complications].
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Acclimatization↗
Biomedical subjects
B Saltin
Publications and source records attributed to B Saltin.
Production of interleukin-6 in contracting human skeletal muscles can account for the exercise-induced increase in plasma interleukin-6.
1. Plasma interleukin (IL)-6 concentration is increased with exercise and it has been demonstrated that contracting muscles can produce IL-The question addressed in the present study was whether the IL-6 production by contracting skeletal muscle is of such a magnitude that it can account for the IL-6 accumulating in the blood. 2. This was studied in six healthy males, who performed one-legged dynamic knee extensor exercise for 5 h at 25 W, which represented 40% of peak power output (Wmax). Arterial-femoral venous (a-fv) differences over the exercising and the resting leg were obtained before and every hour during the exercise. Leg blood flow was measured in parallel by the ultrasound Doppler technique. IL-6 was measured by enzyme-linked immunosorbent assay (ELISA). 3. Arterial plasma concentrations for IL-6 increased 19-fold compared to rest. The a-fv difference for IL-6 over the exercising leg followed the same pattern as did the net IL-6 release. Over the resting leg, there was no significant a-fv difference or net IL-6 release. The work was produced by 2.5 kg of active muscle, which means that during the last 2 h of exercise, the median IL-6 production was 6.8 ng min-1 (kg active muscle)-1 (range, 3.96-9.69 ng min-1 kg-1). 4. The net IL-6 release from the muscle over the last 2 h of exercise was 17-fold higher than the elevation in arterial IL-6 concentration and at 5 h of exercise the net release during 1 min was half of the IL-6 content in the plasma. This indicates a very high turnover of IL-6 during muscular exercise. We suggest that IL-6 produced by skeletal contracting muscle contributes to the maintenance of glucose homeostasis during prolonged exercise.
Adult↗
Heat production in human skeletal muscle at the onset of intense dynamic exercise.
1. We hypothesised that heat production of human skeletal muscle at a given high power output would gradually increase as heat liberation per mole of ATP produced rises when energy is derived from oxidation compared to phosphocreatine (PCr) breakdown and glycogenolysis. 2. Five young volunteers performed 180 s of intense dynamic knee-extensor exercise ( approximately 80 W) while estimates of muscle heat production, power output, oxygen uptake, lactate release, lactate accumulation and ATP and PCr hydrolysis were made. Heat production was determined continuously by (i) measuring heat storage in the contracting muscles, (ii) measuring heat removal to the body core by the circulation, and (iii) estimating heat transfer to the skin by convection and conductance as well as to the body core by lymph drainage. 3. The rate of heat storage in knee-extensor muscles was highest during the first 45 s of exercise (70-80 J s-1) and declined gradually to 14 +/- 10 J s-1 at 180 s. 4. The rate of heat removal by blood was negligible during the first 10 s of exercise, rising gradually to 112 +/- 14 J s-1 at 180 s. The estimated rate of heat release to skin and heat removal via lymph flow was < 2 J s-1 during the first 5 s and increased progressively to 24 +/- 1 J s-1 at 180 s. The rate of heat production increased significantly throughout exercise, being 107 % higher at 180 s compared to the initial 5 s, with half of the increase occurring during the first 38 s, while power output remained essentially constant. 5. The contribution of muscle oxygen uptake and net lactate release to total energy turnover increased curvilinearly from 32 % and 2 %, respectively, during the first 30 s to 86 % and 8 %, respectively, during the last 30 s of exercise. The combined energy contribution from net ATP hydrolysis, net PCr hydrolysis and muscle lactate accumulation is estimated to decline from 37 % to 3 % comparing the same time intervals. 6. The magnitude and rate of elevation in heat production by human skeletal muscle during exercise in vivo could be the result of the enhanced heat liberation during ATP production when aerobic metabolism gradually becomes dominant after PCr and glycogenolysis have initially provided most of the energy.
Adenosine Triphosphate↗
[Metabolic capacity of skeletal muscles and health].
The metabolic capacity of skeletal muscle plays a significant role for insulin sensitivity and the blood lipid profile. The metabolic capacity of the muscle is a function of the individual's physical activity level. This is also true for the content of type IIx muscle fibres, which is reduced and the number of capillaries, which is elevated with muscle usage. Several of these skeletal muscle features are risk factors for or linked with life style-induced diseases such as type II diabetes, hypertension, hyperlipidaemia and obesity. This central role of the skeletal muscle and its functional metabolic capacity for life style diseases highlights the importance of people maintaining daily physical activity. This article focuses on the link between the metabolic capacity of skeletal muscle and the metabolic syndrome and briefly discusses possible metabolic explanations for this relationship. An important aspect is that when skeletal muscle has a high capacity for lipid oxidation more saturated fatty acids are oxidized and more unsaturated fatty acids are built into the phospholipid fraction of the plasma membrane, giving it more fluidity and improved insulin sensitivity. Moreover, the article points at the role of these fatty acids in activating genes via the PPAR-receptor system essential for enzyme and transport proteins in the lipid metabolism.
Exercise↗
[Skeletal muscles, physical activity and health].
The metabolic capacity of skeletal muscle plays a significant role for insulin sensitivity and the blood lipid profile. The metabolic capacity of the muscle is a function of the individual's physical activity level. This is also true for the content of type IIa muscle fibres, which is reduced, and the number of capillaries, which is elevated with muscle usage. Several of these skeletal muscle features are risk factors for or linked with life-style induced diseases such as type II diabetes, hypertension, hyperlipemia and obesity. The central role of the skeletal muscle and its functional metabolic capacity for life style diseases highlights the importance of people maintaining daily physical activity. This article focuses on the link between the metabolic capacity of skeletal muscle and the metabolic syndrome and briefly discusses the explanations for this relationship. As one important aspect if skeletal muscle has a high capacity for lipid oxidation, then more saturated fatty acids are oxidised and more unsaturated fatty acids are built in the phospholipid fraction of the plasma membrane, giving it more fluidity and improved insulin sensitivity. Moreover, the article points at the role of these fatty acids in activating genes via the PPAR-receptor system essential for enzyme and transport proteins in the lipid metabolism.
Diabetes Mellitus, Type 2↗
Muscle, genes and athletic performance.
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Aging↗
Introduction to the Acta Physiologica Scandinavica International Symposium on Skeletal Muscle Oxygen Availability and Utilization.
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Animals↗
The 'lactate paradox', evidence for a transient change in the course of acclimatization to severe hypoxia in lowlanders.
The metabolic response to exercise at high altitude is different from that at sea level, depending on the altitude, the rate of ascent and duration of acclimatization. One apparent metabolic difference that was described in the 1930s is the phenomenon referred to as the 'lactate paradox'. Acute exposure to hypoxia results in higher blood lactate accumulation at submaximal workloads compared with sea level, but peak blood lactate remain the same. Following continued exposure to hypoxia or altitude, blood lactate accumulation at submaximal work and peak blood lactate levels are paradoxically reduced compared with those at sea level. It has recently been shown, however, that, if the exposure to altitude is sufficiently long, blood lactate responses return to those seen at sea level or during acute hypoxia. Thus, to evaluate the 'lactate paradox' phenomenon in relation to time spent at altitude, five Danish lowland climbers were studied at sea level, during acute exposure to hypoxia (10% O2 in N2) and 1, 4 and 6 weeks after arrival in the basecamp of Mt Everest (approximately 5400 m, Nepal). Basecamp was reached after 10 days of gradual ascent from 2800 m. Peak blood lactate levels were similar at sea level (11.0 +/- 0.7 mmol L-1) and during acute hypoxia (9.9 +/- 0.3 mmol L-1), but fell significantly after 1 week of acclimatization to 5400 m (5.6 +/- 0.5 mmol L-1) as predicted by the 'lactate paradox'. After 4 weeks of acclimatization, peak lactate accumulation (7.8 +/- 1.0 mmol L-1) was still lower compared with acute hypoxia but higher than that seen after 1 week of acclimatization. After 6 weeks of acclimatization, 2 days after return to basecamp after reaching the summit or south summit of Mt Everest, peak lactate levels (10.4 +/- 1.1 mmol L-1) were similar to those seen during acute hypoxia. Therefore, these results suggest that the 'lactate paradox' is a transient metabolic phenomenon that is reversed during a prolonged period of exposure to severe hypoxia of more than 6 weeks.
Acclimatization↗
Transcriptional regulation of gene expression in human skeletal muscle during recovery from exercise.
Exercise training elicits a number of adaptive changes in skeletal muscle that result in an improved metabolic efficiency. The molecular mechanisms mediating the cellular adaptations to exercise training in human skeletal muscle are unknown. To test the hypothesis that recovery from exercise is associated with transcriptional activation of specific genes, six untrained male subjects completed 60-90 min of exhaustive one-legged knee extensor exercise for five consecutive days. On day 5, nuclei were isolated from biopsies of the vastus lateralis muscle of the untrained and the trained leg before exercise and from the trained leg immediately after exercise and after 15 min, 1 h, 2 h, and 4 h of recovery. Transcriptional activity of the uncoupling protein 3 (UCP3), pyruvate dehydrogenase kinase 4 (PDK4), and heme oxygenase-1 (HO-1) genes (relative to beta-actin) increased by three- to sevenfold in response to exercise, peaking after 1-2 h of recovery. Increases in mRNA levels followed changes in transcription, peaking between 2 and 4 h after exercise. Lipoprotein lipase and carnitine pamitoyltransferase I gene transcription and mRNA levels showed similar but less dramatic induction patterns, with increases ranging from two- to threefold. In a separate study, a single 4-h bout of cycling exercise (n = 4) elicited from 5 to >20-fold increases in UCP3, PDK4, and HO-1 transcription, suggesting that activation of these genes may be related to the duration or intensity of exercise. These data demonstrate that exercise induces transient increases in transcription of metabolic genes in human skeletal muscle. Moreover, the findings suggest that the cumulative effects of transient increases in transcription during recovery from consecutive bouts of exercise may represent the underlying kinetic basis for the cellular adaptations associated with exercise training.
Actins↗
Human femoral artery diameter in relation to knee extensor muscle mass, peak blood flow, and oxygen uptake.
It is not known whether the diameter of peripheral conduit arteries may impose a limitation on muscle blood flow and oxygen uptake at peak effort in humans, and it is not clear whether these arteries are dimensioned in relation to the tissue volume they supply or, rather, to the type and intensity of muscular activity. In this study, eight humans, with a peak pulmonary oxygen uptake of 3.90 +/- 0.31 (range 2.29-5.03) l/min during ergometer cycle exercise, performed one-legged dynamic knee extensor exercise up to peak effort at 68 +/- 7 W (range 55-100 W). Peak values for knee extensor blood flow (thermodilution) and oxygen uptake of 6.06 +/- 0.74 (range 4.75-9.52) l/min and 874 +/- 124 (range 590-1,521) ml/min, respectively, were achieved. Pulmonary oxygen uptake reached a peak of 1.72 +/- 0.19 (range 1.54-2.33) l/min. Diameters of common and profunda femoral arteries determined by ultrasound Doppler were 10.6 +/- 0.4 (range 8.2-12.7) and 6.0 +/- 0.4 (range 4.5-8.0) mm, respectively. Thigh and quadriceps muscle volume measured by computer tomography were 10.06 +/- 0.66 (range 6.18-10.95) and 2.36 +/- 0.19 (range 1.31-3.27) liters, respectively. The common femoral artery diameter, but not that of the profunda branch, correlated with the thigh volume and quadriceps muscle mass. There were no relationships between either of the diameters and the absolute or muscle mass-related resting and peak values of blood flow and oxygen uptake, peak pulmonary oxygen uptake, or peak power output during knee extensor exercise. However, common femoral artery diameter correlated to peak pulmonary oxygen uptake during ergometer cycle exercise. In conclusion, common and profunda femoral artery diameters are sufficient to ensure delivery to the quadriceps muscle. However, the common branch may impose a limitation during ergometer cycle exercise.
Adult↗
Muscle oxygen kinetics at onset of intense dynamic exercise in humans.
The present study examined the onset and the rate of rise of muscle oxidation during intense exercise in humans and whether oxygen availability limits muscle oxygen uptake in the initial phase of intense exercise. Six subjects performed 3 min of intense one-legged knee-extensor exercise [65.3 +/- 3.7 (means +/- SE) W]. The femoral arteriovenous blood mean transit time (MTT) and time from femoral artery to muscle microcirculation was determined to allow for an examination of the oxygen uptake at capillary level. MTT was 15.3 +/- 1.8 s immediately before exercise, 10.4 +/- 0.7 s after 6 s of exercise, and 4.7 +/- 0.5 s at the end of exercise. Arterial venous O(2) difference (a-v(diff) O(2)) of 18 +/- 5 ml/l before the exercise was unchanged after 2 s, but it increased (P < 0.05) after 6 s of exercise to 43 +/- 10 ml/l and reached 146 +/- 4 ml/l at the end of exercise. Thigh oxygen uptake increased (P < 0.05) from 32 +/- 8 to 102 +/- 28 ml/min after 6 s of exercise and to 789 +/- 88 ml/min at the end of exercise. The time to reach half-peak a-v(diff) O(2) and thigh oxygen uptake was 13 +/- 2 and 25 +/- 3 s, respectively. The difference between thigh oxygen delivery (blood flow x arterial oxygen content) and thigh oxygen uptake increased (P < 0.05) after 6 s and returned to preexercise level after 14 s. The present data suggest that, at the onset of exercise, oxygen uptake of the exercising muscles increases after a delay of only a few seconds, and oxygen extraction peaks after approximately 50 s of exercise. The limited oxygen utilization in the initial phase of intense exercise is not caused by insufficient oxygen availability.
Adult↗
Endurance training does not alter the level of neuronal nitric oxide synthase in human skeletal muscle.
The effect of endurance training on neuronal nitric oxide synthase (nNOS) content and distribution in muscle was investigated. Seven male subjects performed 6 wk of one-legged knee-extensor endurance training (protocol A). Muscle biopsies, obtained from vastus lateralis muscle in the untrained and the trained leg, were analyzed for nNOS protein and activity as well as immunohistochemical distribution of nNOS and endothelial nitric oxide synthase (eNOS). Muscle biopsies were also obtained from another seven male subjects before and after 6 wk of training by endurance running (protocol B) and analyzed for nNOS protein. No difference was found in the amount of nNOS protein in the untrained and the trained muscle either with protocol A or protocol B (P > 0.05). In protocol A, the activity of nNOS was 4.76 +/- 0.56 pmol. mg protein(-1). min(-1) in the control leg, and the level was not different in the trained leg (P > 0.05). nNOS was present in the sarcolemma and cytosol of type I and type II muscle fibers, and the qualitative distribution was similar in untrained and trained muscle. The number of eNOS immunoreactive structures and the number of capillaries per muscle fiber were higher (P < 0.05) after training than before. The present findings demonstrate that, in contrast to findings on animals, nNOS levels remain unaltered with endurance training in humans. Evidence is also provided that endurance training may increase the amount of eNOS, in parallel with an increase in capillaries in human muscle.
Adult↗
Effect of muscle glycogen on glucose, lactate and amino acid metabolism during exercise and recovery in human subjects.
1. Eight subjects performed two-legged exercise, one leg with low and the other with normal muscle glycogen content. The purpose was to study the effect of low initial muscle glycogen content on the metabolic response during 1 h of exercise and 2 h of recovery. This model allows direct comparison of net fluxes of substrates and metabolites over the exercising legs receiving the same arterial inflow. 2. Muscle glycogen breakdown during exercise was 60% lower in the leg with a reduced pre-exercise glycogen concentration and the rate of glucose uptake during exercise was 30% higher. 3. The amount of pyruvate that was oxidized during exercise was calculated to be approximately 450 mmol in the low-glycogen leg and 750 mmol in the normal-glycogen leg, which suggests more fat and amino acid oxidation in the low-glycogen leg. 4. During exercise, there was a significant release of amino acids not metabolized in the muscle, e. g. tyrosine and phenylalanine, only from the low-glycogen leg, suggesting an increased rate of net protein degradation in this leg. 5. The release of tyrosine and phenylalanine from the low-glycogen leg during the exercise period and the change in their muscle concentrations yield a net tyrosine and phenylalanine production rate of 1.4 and 1.5 mmol h-1, respectively. The net rate of protein degradation was then calculated to be 7-12 g h-1. 6. The results suggest that the observed differences in metabolism between the low-glycogen and the normal-glycogen leg are induced by the glycogen level per se, since the legs received the same arterial supply of hormones and substrates.
Adult↗
Decreased skeletal muscle capillary density is related to higher serum levels of low-density lipoprotein cholesterol and apolipoprotein B in men.
The relationships between skeletal muscle morphology, particularly muscle fiber capillary density, and serum lipid profiles were evaluated in 25 non-obese men aged 18 to 36 years (body mass index [BMI], 22.7 +/- 2.5 kg/m2; body fat, 13.6% +/- 4.0%, maximal oxygen uptake [VO2max], 46.2 < or = 6.3 mL/kg/min). Skeletal muscle samples were taken from the vastus lateralis using the needle-biopsy method. The fiber types (I, IIa, and IIx) and their percent distribution, the indices of capillary density, and the diffusion index expressed as the cross-sectional area occupied by one capillary were determined. Blood samples were drawn from the antecubital vein after a 12-hour fast. Based on Pearson's correlation analysis, the number of capillaries around type IIx fiber correlated inversely with the serum level of low-density lipoprotein cholesterol ([LDL-C] r = -.50, P < .05). The number of capillaries per fiber (cap/fiber ratio), number of capillaries per area (cap/mm2), and capillaries around each fiber type correlated inversely with the serum level of apolipoprotein B ([apo B] r = -.40 to -.54, P < .05 to .01). Further, the diffusion index for each fiber type correlated positively with LDL-C and apo B (r = .42 to .50, P < .05 to .01). Among 14 subjects in whom high-density lipoprotein cholesterol (HDL-C) subfractions were analyzed, a positive correlation was found between cap/mm2 and HDL2-C (r = .64, P < .05). Partial correlation analysis showed that these correlations either remain or improve after adjusting for age, VO2max, and body fatness. These results indicate that skeletal muscle capillary density and diffusion capacity are related to lipid and apolipoprotein concentrations for both type I and type II fibers.
Adipose Tissue↗
Skeletal muscle substrate metabolism during exercise: methodological considerations.
The aim of the present article is to evaluate critically the various methods employed in studies designed to quantify precisely skeletal muscle substrate utilization during exercise. In general, the pattern of substrate utilization during exercise can be described well from O2 uptake measurements and the respiratory exchange ratio. However, if the aim is to quantify limb or muscle metabolism, invasive measurements have to be carried out, such as the determination of blood flow, arterio-venous (a-v) difference measurements for O2 and relevant substrates, and biopsies of the active muscle. As many substrates and metabolites may be both taken up and released by muscle at rest and during exercise, isotopes can be used to determine uptake and/or release and also fractional uptake can be accounted for. Furthermore, the use of isotopes opens up further possibilities for the estimation of oxidation rates of various substrates. There are several methodological concerns to be aware of when studying the metabolic response to exercise in human subjects. These concerns include: (1) the muscle mass involved in the exercise is largely unknown (bicycle or treadmill). Moreover, whether the muscle sample obtained from a limb muscle and the substrate and metabolite concentrations are representative can be a problem; (2) the placement of the venous catheter can be critical, and it should be secured so that the blood sample represents blood from the active muscle with a minimum of contamination from other muscles and tissues; (3) the use of net limb glycerol release to estimate lipolysis is probably not valid (triacylglycerol utilization by muscle), since glycerol can be metabolized in skeletal muscle; (4) the precision of blood-borne substrate concentrations during exercise measured by a-v difference is hampered since they become very small due to the high blood flow. Recommendations are given in order to obtain more quantitative and conclusive data in studies investigating the regulatory mechanisms for substrate choice by muscle.
Arteries↗
Muscle protein degradation and amino acid metabolism during prolonged knee-extensor exercise in humans.
The aim of this study was to investigate whether prolonged one-leg knee-extensor exercise enhances net protein degradation in muscle with a normal or low glycogen content. Net amino acid production, as a measure of net protein degradation, was estimated from leg exchange and from changes in the concentrations of amino acids that are not metabolized in skeletal muscle. Experiments were performed at rest and during one-leg knee-extensor exercise in six subjects having one leg with a normal glycogen content and the other with a low glycogen content. Exercise was performed for 90 min at a workload of 60-65% of maximal one-leg power output, starting either with the normal-glycogen or the low-glycogen leg, at random. The net production of threonine, lysine and tyrosine and the sum of the non-metabolized amino acids were 9-20-fold higher (P<0.05) during exercise of the normal-glycogen leg than at rest. Total amino acid production was also 10-fold higher during exercise compared with that at rest (difference not significant). The net production rates of threonine, glycine and tyrosine and of the sum of the non-metabolized amino acids were about 1.5-2.5-fold higher during exercise with the leg with a low glycogen content compared with the leg with a normal glycogen content (P<0.05). Total amino acid production was 1.5-fold higher during exercise for the low-glycogen leg compared with the normal-glycogen leg (difference not significant). These data indicate that prolonged one-leg knee-extensor exercise leads to a substantial increase in net muscle protein degradation, and that a lowering of the starting muscle glycogen content leads to a further increase. The carbon atoms of the branched-chain amino acids (BCAA), glutamate, aspartate and asparagine, liberated by protein degradation, and the BCAA and glutamate extracted in increased amounts from the blood during exercise, are used for the synthesis of glutamine and for tricarboxylic-acid cycle anaplerosis.
Adult↗
Hyperoxia does not increase peak muscle oxygen uptake in small muscle group exercise.
We examined the influence of hyperoxia on peak oxygen uptake (VO2peak) and peripheral gas exchange during exercise with the quadriceps femoris muscle. Young, trained men (n=5) and women (n=3) performed single-leg knee-extension exercise at 70% and 100% of maximum while inspiring normal air (NOX) or 60% O2 (HiOX). Blood was sampled from the femoral vein of the exercising limb and from the contralateral artery. In comparison with NOX, hyperoxic arterial O2 tension (PaO2) increased from 13.5 +/- 0.3 (x +/- SE) to 41.6 +/- 0. 3 kPa, O2 saturation (SaO2) from 98 +/- 0.1 to 100 +/- 0.1%, and O2 concentration (CaO2) from 177 +/- 4 to 186 +/- 4 mL L-1 (all P < 0. 01). Peak exercise femoral venous PO2 (PvO2) was also higher in HiOX (3.68 +/- 0.06 vs. 3.39 +/- 0.7 kPa; P < 0.05), indicating a higher O2 diffusion driving pressure. HiOX femoral venous O2 saturation averaged 36.8 +/- 2.0% as opposed to 33.4 +/- 1.5% in NOX (P < 0.05) and O2 concentration 63 +/- 6 vs. 55 +/- 4 mL L-1 (P < 0.05). Peak exercise quadriceps blood flow (Qleg), measured by the thermo-dilution technique, was lower in HiOX than in NOX, 6.4 +/- 0. 5 vs. 7.3 +/- 0.9 L min-1 (P < 0.05); mean arterial blood pressure at inguinal height was similar in NOX and HiOX at 144 and 142 mmHg, respectively. O2 delivery to the limb (Qleq times CaO2) was not significantly different in HiOX and NOX. VO2peak of the exercising limb averaged 890 mL min-1 in NOX and 801 mL min-1 in HiOX (n.s.) corresponding to 365 and 330 mL min-1 per kg active muscle, respectively. The VO2peak-to-PvO2 ratio was lower (P < 0.05) in HiOX than in NOX suggesting a lower O2 conductance. We conclude that the similar VO2peak values despite higher O2 driving pressure in HiOX indicates a peripheral limitation for VO2peak. This may relate to saturation of the rate of O2 turnover in the mitochondria during exercise with a small muscle group but can also be caused by tissue diffusion limitation related to lower O2 conductance.
Acid-Base Equilibrium↗
PDH activation by dichloroacetate reduces TCA cycle intermediates at rest but not during exercise in humans.
We hypothesized that dichloroacetate (DCA), which stimulates the pyruvate dehydrogenase complex (PDH), would attenuate the increase in muscle tricarboxylic acid cycle intermediates (TCAI) during exercise by increasing the oxidative disposal of pyruvate and attenuating the flux through anaplerotic pathways. Six subjects were infused with either saline (Con) or DCA (100 mg/kg body mass) and then performed a moderate leg kicking exercise for 15 min, followed immediately by intense exercise until exhaustion (Exh; approximately 4 min). Resting active fraction of PDH (PDH(a)) was markedly increased (P </= 0.05) after DCA vs. Con (2.65 +/- 0.27 vs. 0.64 +/- 0.07 mmol. min(-1). kg wet wt(-1)); however, there were no differences between trials after 1 or 15 min of exercise or at Exh. The sum of five measured TCAI (SigmaTCAI; approximately 90% of total TCAI pool) was lower (P </= 0.05) after DCA vs. Con at rest (0. 78 +/- 0.11 vs. 1.52 +/- 0.23 mmol/kg dry wt, respectively). However, the net increase in muscle TCAI during the first minute of exercise was higher (P </= 0.05) in the DCA trial vs. Con (3.05 +/- 0.45 vs. 2.44 +/- 0.55 mmol. min(-1). kg dry wt(-1), respectively), and consequently, the SigmaTCAI was not different between trials during exercise. We conclude that DCA reduced TCAI pool size at rest by increasing the flux through PDH and diverting pyruvate away from anaplerotic pathways. The reason for the similar absolute increase in TCAI during exercise is not clear but may be related to 1) an initial mismatch between glycolytic flux and PDH flux that provided sufficient pyruvate for anaplerosis in both trials; or 2) a transient inhibition of PDH flux during the DCA trial due to an elevated resting acetyl-CoA-to-CoASH ratio, which augmented the anaplerotic flux of carbon during the rest-to-work transition.
Adult↗