Dichloroacetate reveals the presence of metabolic inertia at the start of exercise in rainbow trout (Oncorhynchus mykiss, Walbaum 1792).

A lag in the increase in oxygen consumption (MO2 ) occurs at the start of sustainable exercise in trout. Waterborne dichloroacetate (0.58 and 3.49 mmol l-1 ), a compound which activates pyruvate dehydrogenase (PDH) by inhibiting PDH kinase in muscle, accelerates the increase in MO2 during the first 10 min of sustainable exercise when velocity is elevated to 75% critical swimming speed in a swim tunnel. There are no effects on MO2 thereafter or at rest. This indicates that a delay in PDH activation ("metabolic inertia") contributes to the lag phenomenon.

Resting metabolic rate and skeletal muscle SERCA and Na+ /K+ ATPase activities are not affected by fish oil supplementation in healthy older adults.

Omega-3 polyunsaturated fatty acids (PUFAs) have unique properties purported to influence several aspects of metabolism, including energy expenditure and protein function. Supplementing with n-3 PUFAs may increase whole-body resting metabolic rate (RMR), by enhancing Na+ /K+ ATPase (NKA) activity and reducing the efficiency of sarcoplasmic reticulum (SR) Ca2+ ATPase (SERCA) activity by inducing a Ca2+ leak-pump cycle. The purpose of this study was to examine the effects of fish oil (FO) on RMR, substrate oxidation, and skeletal muscle SERCA and NKA pump function in healthy older individuals. Subjects (n = 16 females; n = 8 males; 65 ± 1 years) were randomly assigned into groups supplemented with either olive oil (OO) (5 g/day) or FO (5 g/day) containing 2 g/day eicosapentaenoic acid and 1 g/day docosahexaenoic acid for 12 weeks. Participants visited the laboratory for RMR and substrate oxidation measurements after an overnight fast at weeks 0 and 12. Skeletal muscle biopsies were taken during weeks 0 and 12 for analysis of NKA and SERCA function and protein content. There was a main effect of time with decrease in RMR (5%) and fat oxidation (18%) in both the supplementation groups. The kinetic parameters of SERCA and NKA maximal activity, as well as the expression of SR and NKA proteins, were not affected after OO and FO supplementation. In conclusion, these results suggest that FO supplementation is not effective in altering RMR, substrate oxidation, and skeletal muscle SERCA and NKA protein levels and activities, in healthy older men and women.

Low-load resistance training to task failure with and without blood flow restriction: muscular functional and structural adaptations.

The application of blood flow restriction (BFR) during resistance exercise is increasingly recognized for its ability to improve rehabilitation and for its effectiveness in increasing muscle hypertrophy and strength among healthy populations. However, direct comparison of the skeletal muscle adaptations to low-load resistance exercise (LL-RE) and low-load BFR resistance exercise (LL-BFR) performed to task failure is lacking. Using a within-subject design, we examined whole muscle group and skeletal muscle adaptations to 6 wk of LL-RE and LL-BFR training to repetition failure. Muscle strength and size outcomes were similar for both types of training, despite ~33% lower total exercise volume (load × repetition) with LL-BFR than LL-RE (28,544 ± 1,771 vs. 18,949 ± 1,541 kg, P = 0.004). After training, only LL-BFR improved the average power output throughout the midportion of a voluntary muscle endurance task. Specifically, LL-BFR training sustained an 18% greater power output from baseline and resulted in a greater change from baseline than LL-RE (19 ± 3 vs. 3 ± 4 W, P = 0.008). This improvement occurred despite histological analysis revealing similar increases in capillary content of type I muscle fibers following LL-RE and LL-BFR training, which was primarily driven by increased capillary contacts (4.53 ± 0.23 before training vs. 5.33 ± 0.27 and 5.17 ± 0.25 after LL-RE and LL-BFR, respectively, both P < 0.05). Moreover, maximally supported mitochondrial respiratory capacity increased only in the LL-RE leg by 30% from baseline (P = 0.006). Overall, low-load resistance training increased indexes of muscle oxidative capacity and strength, which were not further augmented with the application of BFR. However, performance on a muscle endurance test was improved following BFR training.

Assessment of Na+/K+ ATPase Activity in Small Rodent and Human Skeletal Muscle Samples.

INTRODUCTION: In skeletal muscle, the Na/K ATPase (NKA) plays essential roles in processes linked to muscle contraction, fatigue, and energy metabolism; however, very little information exists regarding the regulation of NKA activity. The scarcity of information regarding NKA function in skeletal muscle likely stems from methodological constraints, as NKA contributes minimally to total cellular ATP utilization, and therefore contamination from other ATPases prevents the assessment of NKA activity in muscle homogenates. Here we introduce a method that improves accuracy and feasibility for the determination of NKA activity in small rodent muscle samples (5-10 mg) and in human skeletal muscle. METHODS: Skeletal muscle homogenates from mice (n = 6) and humans (n = 3) were used to measure NKA and sarcoplasmic reticulum Ca ATPase (SERCA) activities with the addition of specific ATPase inhibitors to minimize "background noise." RESULTS: We observed that myosin ATPase activity was the major interfering factor for estimation of NKA activity in skeletal muscle homogenates, as the addition of 25 µM of blebbistatin, a specific myosin ATPase inhibitor, considerably minimized "background noise" (threefold) and enabled the determination of NKA maximal activity with values three times higher than previously reported. The specificity of the assay was demonstrated after the addition of 2 mM ouabain, which completely inhibited NKA. On the other hand, the addition of blebbistatin did not affect the ability to measure SERCA function. The coefficient of variation for NKA and SERCA assays were 6.2% and 4.4%, respectively. CONCLUSION: The present study has improved the methodology to determine NKA activity. We further show the feasibility of measuring NKA and SERCA activities from a common muscle homogenate. This methodology is expected to aid in our long-term understanding of how NKA affects skeletal muscle metabolic homeostasis and contractile function in diverse situations.

Incorporation of Omega-3 Fatty Acids Into Human Skeletal Muscle Sarcolemmal and Mitochondrial Membranes Following 12 Weeks of Fish Oil Supplementation.

Fish oil (FO) supplementation in humans results in the incorporation of omega-3 fatty acids (FAs) eicosapentaenoic acid (EPA; C20:5) and docosahexaenoic acid (DHA; C20:6) into skeletal muscle membranes. However, despite the importance of membrane composition in structure-function relationships, a paucity of information exists regarding how different muscle membranes/organelles respond to FO supplementation. Therefore, the purpose of the present study was to determine the effects 12 weeks of FO supplementation (3g EPA/2g DHA daily) on the phospholipid composition of sarcolemmal and mitochondrial fractions, as well as whole muscle responses, in healthy young males. FO supplementation increased the total phospholipid content in whole muscle (57%; p < 0.05) and the sarcolemma (38%; p = 0.05), but did not alter the content in mitochondria. The content of omega-3 FAs, EPA and DHA, were increased (+3-fold) in whole muscle, and mitochondrial membranes, and as a result the omega-6/omega-3 ratios were dramatically decreased (-3-fold), while conversely the unsaturation indexes were increased. Intriguingly, before supplementation the unsaturation index (UI) of sarcolemmal membranes was ∼3 times lower (p < 0.001) than either whole muscle or mitochondrial membranes. While supplementation also increased DHA within sarcolemmal membranes, EPA was not altered, and as a result the omega-6/omega-3 ratio and UI of these membranes were not altered. All together, these data revealed that mitochondrial and sarcolemmal membranes display unique phospholipid compositions and responses to FO supplementation.

Slow V˙O2 kinetics in acute hypoxia are not related to a hyperventilation-induced hypocapnia.

We examined whether slower pulmonary O2 uptake (V˙O2p) kinetics in hypoxia is a consequence of: a) hypoxia alone (lowered arterial O2 pressure), b) hyperventilation-induced hypocapnia (lowered arterial CO2 pressure), or c) a combination of both. Eleven participants performed 3-5 repetitions of step-changes in cycle ergometer power output from 20W to 80% lactate threshold in the following conditions: i) normoxia (CON; room air); ii) hypoxia (HX, inspired O2 = 12%; lowered end-tidal O2 pressure [PETO2] and end-tidal CO2 pressure [PETCO2]); iii) hyperventilation (HV; increased PETO2 and lowered PETCO2); and iv) normocapnic hypoxia (NC-HX; lowered PETO2 and PETCO2 matched to CON). Ventilation was increased (relative to CON) and matched between HX, HV, and NC-HX conditions. During each condition VO2p˙ was measured and phase II V˙O2p kinetics were modeled with a mono-exponential function. The V˙O2p time constant was different (p < 0.05) amongst all conditions: CON, 26 ±â€¯11s; HV, 36 ±â€¯14s; HX, 46 ±â€¯14s; and NC-HX, 52 ±â€¯13s. Hypocapnia may prevent further slowing of V˙O2p kinetics in hypoxic exercise.

Beetroot Juice Increases Human Muscle Force without Changing Ca2+-Handling Proteins.

Dietary inorganic nitrate (NO3) supplementation improves skeletal muscle (SkM) contractile efficiency, and although rodent literature has suggested improvements in calcium handling or redox modifications as likely explanations, the direct mechanism of action in humans remains unknown. PURPOSE: This study aimed to examine the effects of 7 d of beetroot juice (BRJ) supplementation on SkM contractile characteristics and function. METHODS: Recreationally active males (n = 8) underwent transcutaneous electrical muscle stimulation of the vastus lateralis for the evaluation of contractile characteristics before and after 7 d of BRJ supplementation (280 mL·d, ~26 mmol NO3). An additional group of individuals (n = 8) followed the same supplementation protocol but underwent SkM biopsies pre- and post-supplementation for the determination of proteins associated with calcium handling via Western blotting, and the ratio of reduced/oxidized glutathione (GSH:GSSG), an indicator of cellular redox state, via high-performance liquid chromatography (HPLC). RESULTS: After supplementation, there was no change in maximal voluntary force production (602 ± 50 vs 596 ± 56 N) or electrically induced tetanic contractions. By contrast, force production was increased at 10 Hz electrical stimulation (41.1% ± 2.3% vs 37.6% ± 2.4% of peak force, P < 0.05), as was peak twitch tension (164.0 ± 12.5 vs 136.5 ± 7.2 N, P < 0.01) and maximal rates of force development and relaxation (3582.8 ± 382.3 vs 2575.7 ± 196.2 and -2752.4 ± 423.9 vs -2104.4 ± 249.0 N·s, respectively, P < 0.05). Despite these measurements implicating a change in calcium handling, the content of associated proteins (SERCA1a, SERCA2a, dihydropyradine receptor, ryanodine receptor, and calsequestrin) and the GSH:GSSG ratio were unaltered by BRJ. CONCLUSION: BRJ supplementation increases force production at low-stimulation frequencies; however, in human SkM, this is independent of changes in redox stress or the expression of protein targets associated with calcium handling.

Mild Dehydration Does Not Influence Performance Or Skeletal Muscle Metabolism During Simulated Ice Hockey Exercise In Men.

This study determined whether mild dehydration influenced skeletal muscle glycogen use, core temperature or performance during high-intensity, intermittent cycle-based exercise in ice hockey players vs. staying hydrated with water. Eight males (21.6 ± 0.4 yr, 183.5 ± 1.6 cm, 83.9 ± 3.7 kg, 50.2 ± 1.9 ml·kg-1·min-1) performed two trials separated by 7 days. The protocol consisted of 3 periods (P) containing 10 × 45-s cycling bouts at ~133% VO2max, followed by 135 s of passive rest. Subjects drank no fluid and dehydrated during the protocol (NF), or maintained body mass by drinking WATER. Muscle biopsies were taken at rest, immediately before and after P3. Subjects were mildly dehydrated (-1.8% BM) at the end of P3 in the NF trial. There were no differences between the NF and WATER trials for glycogen use (P1+P2; 350.1 ± 31.9 vs. 413.2 ± 33.2, P3; 103.5 ± 16.2 vs. 131.5 ± 18.9 mmol·kg dm-1), core temperature (P1; 37.8 ± 0.1 vs. 37.7 ± 0.1, P2; 38.2 ± 0.1 vs. 38.1 ± 0.1, P3; 38.3 ± 0.1 vs. 38.2 ± 0.1 °C) or performance (P1; 156.3 ± 7.8 vs. 154.4 ± 8.2, P2; 150.5 ± 7.8 vs. 152.4 ± 8.3, P3; 144.1 ± 8.7 vs. 148.4 ± 8.7 kJ). This study demonstrated that typical dehydration experienced by ice hockey players (~1.8% BM loss), did not affect glycogen use, core temperature, or voluntary performance vs. staying hydrated by ingesting water during a cycle-based simulation of ice hockey exercise in a laboratory environment.

The effect of dehydration on muscle metabolism and time trial performance during prolonged cycling in males.

This study combined overnight fluid restriction with lack of fluid intake during prolonged cycling to determine the effects of dehydration on substrate oxidation, skeletal muscle metabolism, heat shock protein 72 (Hsp72) response, and time trial (TT) performance. Nine males cycled at ~65% VO2peak for 90 min followed by a TT (6 kJ/kg BM) either with fluid (HYD) or without fluid (DEH). Blood samples were taken every 20 min and muscle biopsies were taken at 0, 45, and 90 min of exercise and after the TT. DEH subjects started the trial with a -0.6% BM from overnight fluid restriction and were dehydrated by 1.4% after 45 min, 2.3% after 90 min of exercise, and 3.1% BM after the TT. There were no significant differences in oxygen uptake, carbon dioxide production, or total sweat loss between the trials. However, physiological parameters (heart rate [HR], rate of perceived exertion, core temperature [Tc], plasma osmolality [Posm], plasma volume [Pvol] loss, and Hsp72), and carbohydrate (CHO) oxidation and muscle glycogen use were greater during 90 min of moderate cycling when subjects progressed from 0.6% to 2.3% dehydration. TT performance was 13% slower when subjects began 2.3% and ended 3.1% dehydrated. Throughout the TT, Tc, Posm, blood and muscle lactate [La], and serum Hsp72 were higher, even while working at a lower power output (PO). The accelerated muscle glycogen use during 90 min of moderate intensity exercise with DEH did not affect subsequent TT performance, rather augmented Tc, RPE and the additional physiological factors were more important in slowing performance when dehydrated.

Effect of voluntary hyperventilation with supplemental CO2 on pulmonary O2 uptake and leg blood flow kinetics during moderate-intensity exercise.

Pulmonary O2 uptake (V(O2p)) and leg blood flow (LBF) kinetics were examined at the onset of moderate-intensity exercise, during hyperventilation with and without associated hypocapnic alkalosis. Seven male subjects (25 ± 6 years old; mean ± SD) performed alternate-leg knee-extension exercise from baseline to moderate-intensity exercise (80% of estimated lactate threshold) and completed four to six repetitions for each of the following three conditions: (i) control [CON; end-tidal partial pressure of CO2 (P(ET, CO2)) ~40 mmHg], i.e. normal breathing with normal inspired CO2 (0.03%); (ii) hypocapnia (HYPO; P(ET, CO2) ~20 mmHg), i.e. sustained hyperventilation with normal inspired CO2 (0.03%); and (iii) normocapnia (NORMO; P(ET, CO2) ~40 mmHg), i.e. sustained hyperventilation with elevated inspired CO2 (~5%). The V(O2p) was measured breath by breath using mass spectrometry and a volume turbine. Femoral artery mean blood velocity was measured by Doppler ultrasound, and LBF was calculated from femoral artery diameter and mean blood velocity. Phase 2 V(O2p) kinetics (τV(O2p)) was different (P < 0.05) amongst all three conditions (CON, 19 ± 7 s; HYPO, 43 ± 17 s; and NORMO, 30 ± 8 s), while LBF kinetics (τLBF) was slower (P < 0.05) in HYPO (31 ± 9 s) compared with both CON (19 ± 3 s) and NORMO (20 ± 6 s). Similar to previous findings, HYPO was associated with slower V(O2p) and LBF kinetics compared with CON. In the present study, preventing the fall in end-tidal P(CO2) (NORMO) restored LBF kinetics, but not V(O2p) kinetics, which remained 'slowed' relative to CON. These data suggest that the hyperventilation manoeuvre itself (i.e. independent of induced hypocapnic alkalosis) may contribute to the slower V(O2p) kinetics observed during HYPO.

Pulmonary gas exchange and acid-base balance during exercise.

As the first step in the oxygen-transport chain, the lung has a critical task: optimizing the exchange of respiratory gases to maintain delivery of oxygen and the elimination of carbon dioxide. In healthy subjects, gas exchange, as evaluated by the alveolar-to-arterial PO2 difference (A-aDO2), worsens with incremental exercise, and typically reaches an A-aDO2 of approximately 25 mmHg at peak exercise. While there is great individual variability, A-aDO2 is generally largest at peak exercise in subjects with the highest peak oxygen consumption. Inert gas data has shown that the increase in A-aDO2 is explained by decreased ventilation-perfusion matching, and the development of a diffusion limitation for oxygen. Gas exchange data does not indicate the presence of right-to-left intrapulmonary shunt developing with exercise, despite recent data suggesting that large-diameter arteriovenous shunt vessels may be recruited with exercise. At the same time, multisystem mechanisms regulate systemic acid-base balance in integrative processes that involve gas exchange between tissues and the environment and simultaneous net changes in the concentrations of strong and weak ions within, and transfer between, extracellular and intracellular fluids. The physicochemical approach to acid-base balance is used to understand the contributions from independent acid-base variables to measured acid-base disturbances within contracting skeletal muscle, erythrocytes and noncontracting tissues. In muscle, the magnitude of the disturbance is proportional to the concentrations of dissociated weak acids, the rate at which acid equivalents (strong acid) accumulate and the rate at which strong base cations are added to or removed from muscle.

AMP-activated protein kinase is required for exercise-induced peroxisome proliferator-activated receptor co-activator 1 translocation to subsarcolemmal mitochondria in skeletal muscle.

In skeletal muscle, mitochondria exist as two subcellular populations known as subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondria. SS mitochondria preferentially respond to exercise training, suggesting divergent transcriptional control of the mitochondrial genomes. The transcriptional co-activator peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α) and mitochondrial transcription factor A (Tfam) have been implicated in the direct regulation of the mitochondrial genome in mice, although SS and IMF differences may exist, and the potential signalling events regulating the mitochondrial content of these proteins have not been elucidated. Therefore, we examined the potential for PGC-1α and Tfam to translocate to SS and IMF mitochondria in human subjects, and performed experiments in rodents to identify signalling mechanisms regulating these translocation events. Acute exercise in humans and rats increased PGC-1α content in SS but not IMF mitochondria. Acute exposure to 5-aminoimidazole-4-carboxamide-1-ß-ribofuranoside in rats recapitulated the exercise effect of increased PGC-1α protein within SS mitochondria only, suggesting that AMP-activated protein kinase (AMPK) signalling is involved. In addition, rendering AMPK inactive (AMPK kinase dead mice) prevented exercise-induced PGC-1α translocation to SS mitochondria, further suggesting that AMPK plays an integral role in these translocation events. In contrast to the conserved PGC-1α translocation to SS mitochondria across species (humans, rats and mice), acute exercise only increased mitochondrial Tfam in rats. Nevertheless, in rat resting muscle PGC-1α and Tfam co-immunoprecipate with α-tubulin, suggesting a common cytosolic localization. These data suggest that exercise causes translocation of PGC-1α preferentially to SS mitochondria in an AMPK-dependent manner.

Increase in skeletal-muscle glycogenolysis and perceived exertion with progressive dehydration during cycling in hydrated men.

This study investigated the effects of progressive mild dehydration during cycling on whole-body substrate oxidation and skeletal-muscle metabolism in recreationally active men. Subjects (N = 9) cycled for 120 min at ~65% peak oxygen uptake (VO2peak 22.7 °C, 32% relative humidity) with water to replace sweat losses (HYD) or without fluid (DEH). Blood samples were taken at rest and every 20 min, and muscle biopsies were taken at rest and at 40, 80, and 120 min of exercise. Subjects lost 0.8%, 1.8%, and 2.7% body mass (BM) after 40, 80, and 120 min of cycling in the DEH trial while sweat loss was not significantly different between trials. Heart rate was greater in the DEH trial from 60 to 120 min, and core temperature was greater from 75 to 120 min. Rating of perceived exertion was higher in the DEH trial from 30 to 120 min. There were no differences in VO2, respiratory-exchange ratio, total carbohydrate (CHO) oxidation (HYD 312 ± 9 vs. DEH 307 ± 10 g), or sweat rate between trials. Blood lactate was significantly greater in the DEH trial from 20 to 120 min with no difference in plasma free fatty acids or epinephrine. Glycogenolysis was significantly greater (24%) over the entire DEH vs. HYD trial (433 ± 44 vs. 349 ± 27 mmol · kg-1 · dm-1). In conclusion, dehydration of <2% BM elevated physiological parameters and perceived exertion, as well as muscle glycogenolysis, during exercise without affecting whole-body CHO oxidation.

Mitochondrial creatine kinase activity and phosphate shuttling are acutely regulated by exercise in human skeletal muscle.

Energy transfer between mitochondrial and cytosolic compartments is predominantly achieved by creatine-dependent phosphate shuttling (PCr/Cr) involving mitochondrial creatine kinase (miCK). However, ADP/ATP diffusion through adenine nucleotide translocase (ANT) and voltage-dependent anion carriers (VDACs) is also involved in this process. To determine if exercise alters the regulation of this system, ADP-stimulated mitochondrial respiratory kinetics were assessed in permeabilized muscle fibre bundles (PmFBs) taken from biopsies before and after 2 h of cycling exercise (60% ) in nine lean males. Concentrations of creatine (Cr) and phosphocreatine (PCr) as well as the contractile state of PmFBs were manipulated in situ. In the absence of contractile signals (relaxed PmFBs) and miCK activity (no Cr), post-exercise respiratory sensitivity to ADP was reduced in situ (up to 126% higher apparent K(m) to ADP) suggesting inhibition of ADP/ATP diffusion between matrix and cytosolic compartments (possibly ANT and VDACs). However this effect was masked in the presence of saturating Cr (no effect of exercise on ADP sensitivity). Given that the role of ANT is thought to be independent of Cr, these findings suggest ADP/ATP, but not PCr/Cr, cycling through the outer mitochondrial membrane (VDACs) may be attenuated in resting muscle after exercise. In contrast, in contracted PmFBs, post-exercise respiratory sensitivity to ADP increased with miCK activation (saturating Cr; 33% lower apparent K(m) to ADP), suggesting prior exercise increases miCK sensitivity in situ. These observations demonstrate that exercise increases miCK-dependent respiratory sensitivity to ADP, promoting mitochondrial-cytosolic energy exchange via PCr/Cr cycling, possibly through VDACs. This effect may mask an underlying inhibition of Cr-independent ADP/ATP diffusion. This enhanced regulation of miCK-dependent phosphate shuttling may improve energy homeostasis through more efficient coupling of oxidative phosphorylation to perturbations in cellular energy charge during subsequent bouts of contraction.

Effects of dehydration during cycling on skeletal muscle metabolism in females.

INTRODUCTION: This study investigated the effects of progressive dehydration on the time course of changes to whole body substrate oxidation and skeletal muscle metabolism during 120 min of cycling in hydrated females. METHODS: Subjects (n = 9) cycled for 120 min at approximately 65% VO(2peak) on two occasions: with no fluid (DEH) and with fluid (HYD) replacement to match sweat losses. Venous blood samples were taken at rest and every 20 min and muscle biopsies taken at 0, 60, and 120 min of exercise. RESULTS: DEH subjects lost 0.9% body mass from 0 to 60 min and 1.1% from 60 to 120 min (2.0% total). HR and core temperature (Tc) were significantly greater from 30 to 120 min, plasma volume (Pvol) loss from 40 to 120 min, and RPE from 60 to 120 min in the DEH trial. There were no differences in VO(2) or sweat loss between trials. RER (HYD, 0.85 ± 0.01, vs. DEH, 0.87 ± 0.01) and total CHO oxidation (175 ± 17 vs. 191 ± 17 g) were higher in the DEH trial. Blood (La) was significantly higher in the DEH trial, with no change in plasma free fatty acid and epinephrine concentrations. Muscle glycogenolysis was 31% greater in the DEH trial (252 ± 49 vs. 330 ± 33 mmol.kg(-1) dry muscle), and muscle (La) was also higher at 60 min. CONCLUSION: Progressive dehydration significantly increased HR, Tc, RPE, Pvol loss, whole body CHO oxidation, and muscle glycogenolysis, and these changes were already apparent in the first hour of exercise when body mass losses were ≤ 1%. The increased muscle glycogenolysis with DEH appeared to be due to increased core and muscle temperature, secondary to less efficient movement of heat from the core to the periphery.

Acute endurance exercise increases plasma membrane fatty acid transport proteins in rat and human skeletal muscle.

Fatty acid transport proteins are present on the plasma membrane and are involved in the uptake of long-chain fatty acids into skeletal muscle. The present study determined whether acute endurance exercise increased the plasma membrane content of fatty acid transport proteins in rat and human skeletal muscle and whether the increase was accompanied by an increase in long-chain fatty acid transport in rat skeletal muscle. Sixteen subjects cycled for 120 min at ∼60 ± 2% Vo(2) peak. Two skeletal muscle biopsies were taken at rest and again following cycling. In a parallel study, eight Sprague-Dawley rats ran for 120 min at 20 m/min, whereas eight rats acted as nonrunning controls. Giant sarcolemmal vesicles were prepared, and protein content of FAT/CD36 and FABPpm was measured in human and rat vesicles and whole muscle homogenate. Palmitate uptake was measured in the rat vesicles. In human muscle, plasma membrane FAT/CD36 and FABPpm protein contents increased 75 and 20%, respectively, following 120 min of exercise. In rat muscle, plasma membrane FAT/CD36 and FABPpm increased 20 and 30%, respectively, and correlated with a 30% increase in palmitate transport following 120 min of running. These data suggest that the translocation of FAT/CD36 and FABPpm to the plasma membrane in rat skeletal muscle is related to the increase in fatty acid transport and oxidation that occurs with endurance running. This study is also the first to demonstrate that endurance cycling induces an increase in plasma membrane FAT/CD36 and FABPpm content in human skeletal muscle, which is predicted to increase fatty acid transport.

Effects of gas exchange on acid-base balance.

This paper describes the interactions between ventilation and acid-base balance under a variety of conditions including rest, exercise, altitude, pregnancy, and various muscle, respiratory, cardiac, and renal pathologies. We introduce the physicochemical approach to assessing acid-base status and demonstrate how this approach can be used to quantify the origins of acid-base disorders using examples from the literature. The relationships between chemoreceptor and metaboreceptor control of ventilation and acid-base balance summarized here for adults, youth, and in various pathological conditions. There is a dynamic interplay between disturbances in acid-base balance, that is, exercise, that affect ventilation as well as imposed or pathological disturbances of ventilation that affect acid-base balance. Interactions between ventilation and acid-base balance are highlighted for moderate- to high-intensity exercise, altitude, induced acidosis and alkalosis, pregnancy, obesity, and some pathological conditions. In many situations, complete acid-base data are lacking, indicating a need for further research aimed at elucidating mechanistic bases for relationships between alterations in acid-base state and the ventilatory responses.

The relationship between human skeletal muscle pyruvate dehydrogenase phosphatase activity and muscle aerobic capacity.

Pyruvate dehydrogenase (PDH) is a mitochondrial enzyme responsible for regulating the conversion of pyruvate to acetyl-CoA for use in the tricarboxylic acid cycle. PDH is regulated through phosphorylation and inactivation by PDH kinase (PDK) and dephosphorylation and activation by PDH phosphatase (PDP). The effect of endurance training on PDK in humans has been investigated; however, to date no study has examined the effect of endurance training on PDP in humans. Therefore, the purpose of this study was to examine differences in PDP activity and PDP1 protein content in human skeletal muscle across a range of muscle aerobic capacities. This association is important as higher PDP activity and protein content will allow for increased activation of PDH, and carbohydrate oxidation. The main findings of this study were that 1) PDP activity (r(2) = 0.399, P = 0.001) and PDP1 protein expression (r(2) = 0.153, P = 0.039) were positively correlated with citrate synthase (CS) activity as a marker for muscle aerobic capacity; 2) E1α (r(2) = 0.310, P = 0.002) and PDK2 protein (r(2) = 0.229, P =0.012) are positively correlated with muscle CS activity; and 3) although it is the most abundant isoform, PDP1 protein content only explained ∼ 18% of the variance in PDP activity (r(2) = 0.184, P = 0.033). In addition, PDP1 in combination with E1α explained ∼ 38% of the variance in PDP activity (r(2) = 0.383, P = 0.005), suggesting that there may be alternative regulatory mechanisms of this enzyme other than protein content. These data suggest that with higher muscle aerobic capacity (CS activity) there is a greater capacity for carbohydrate oxidation (E1α), in concert with higher potential for PDH activation (PDP activity).