Carbohydrate supplementation during prolonged cycling exercise spares muscle glycogen but does not affect intramyocellular lipid use

Using contemporary stable-isotope methodology and fluorescence microscopy, we assessed the impact of carbohydrate supplementation on whole-body and fiber-type-specific intramyocellular triacylglycerol (IMTG) and glycogen use during prolonged endurance exercise. Ten endurance-trained male subjects were studied twice during 3 h of cycling at 63 ± 4% of maximal O₂ uptake with either glucose ingestion (CHO trial; 0.7 g CHO kg⁻¹ h⁻¹) or without (CON placebo trial; water only). Continuous infusions with [U-¹³C] palmitate and [6,6-²H₂] glucose were applied to quantify plasma free fatty acids (FFA) and glucose oxidation rates and to estimate intramyocellular lipid and glycogen use. Before and after exercise, muscle biopsy samples were taken to quantify fiber-type-specific IMTG and glycogen content. Plasma glucose rate of appearance (R _a) and carbohydrate oxidation rates were substantially greater in the CHO vs CON trial. Carbohydrate supplementation resulted in a lower muscle glycogen use during the first hour of exercise in the CHO vs CON trial, resulting in a 38 ± 19 and 57 ± 22% decreased utilization in type I and II muscle-fiber glycogen content, respectively. In the CHO trial, both plasma FFA R _a and subsequent plasma FFA concentrations were lower, resulting in a 34 ± 12% reduction in plasma FFA oxidation rates during exercise (P < 0.05). Carbohydrate intake did not augment IMTG utilization, as fluorescence microscopy revealed a 76 ± 21 and 78 ± 22% reduction in type I muscle-fiber lipid content in the CHO and CON trial, respectively. We conclude that carbohydrate supplementation during prolonged cycling exercise does not modulate IMTG use but spares muscle glycogen use during the initial stages of exercise in endurance-trained men.     

Fuel substrate turnover and oxidation and glycogen sparing with carbohydrate ingestion in non-carbohydrate-loaded cyclists

This study examined the effects of ingesting 500 ml/h of either a 10% carbohydrate (CHO) drink (CI) or placebo (PI) on splanchnic glucose appearance rate (endogenous + exogenous) (R _a), plasma glucose oxidation and muscle glycogen utilisation in 17, non-carbohydrate-loaded, male, endurance-trained cyclists who rode for 180 min at 70% of maximum oxygen uptake. Mean muscle glycogen content at the start of exercise was 130 ± 6 mmol/kg ww; (mean ± SEM). Total CHO oxidation was similar in CI and PI subjects and declined during the trial. R _a increased significantly during the trial (P < 0.05) in both groups. Plasma glucose oxidation also increased significantly during the trial, reaching a plateau in the PI subjects, but was significantly (P < 0.05) higher in CI than PI subjects at the end of exercise [(98 ± 14 vs. 72 ± 10 μmol/min/kg fat-free mass) (FFM) (1.34 ± 0.19 vs. 0.93 ± 0.13 g/min)]. However, mean endogenous R _a was significantly (P < 0.05) lower in the CI than PI subjects throughout exercise (35 ± 7 vs. 54 ± 6 μmol/min/kg FFM), as was the oxidation of endogenous plasma glucose, which remained almost constant in CI subjects, and reached values at the end of exercise of 42 ± 13 and 72 ± 10 μmol/min/kg FFM in the CI and PI groups respectively. Of the 150 g CHO ingested during the trial, 50% was oxidised. Muscle glycogen disappearance was identical during the first 2 h of exercise in both groups and continued at the same rate in PI subjects, however no net muscle glycogen disappearance occurred during the final hour in CI subjects. We conclude that ingestion of 500 ml/h of a 10% CHO solution during prolonged exercise in non carbohydrate loaded subjects has a marked liver glycogen-sparing effect or causes a reduction in gluconeogenesis, or both, maintains plasma glucose concentration and has a muscle glycogen-sparing effect. Received: 25 August 1995/Received after revision: 25 March 1996/Accepted: 29 April 1996     

Fuel metabolism during ultra-endurance exercise

 Cyclists either ingested 300 ml 100 g/l U-[¹⁴C] glucose solution every 30 min during 6 h rides at 55% of VO_2max (n=6) or they consumed unlabelled glucose and were infused with U-[¹⁴C] lactate (n=5). Maintenance of euglycaemia limited rises in circulating free fatty acids, noradrenaline and adrenaline concentrations to 0.9±0.1 mM, 27±4 nM and 2.0±0.5 nM, respectively, and sustained the oxidation of glucose and lactate. As muscle glycogen oxidation declined from 100±13 to 71±9 μmol/min/kg in the last 3 h of exercise, glucose and lactate oxidation and interconversion rates remained at approximately 60 and 50 and at about 4 and 5 μmol/min/kg, respectively. Continued high rates of carbohydrate oxidation led to a total oxidation of around 270 g glucose, 130 g plasma lactate and 530 g muscle glycogen. Oxidation of some 530 g of muscle glycogen far exceeded the predicted (about 250 g) initial glycogen content of the active muscles and suggested that there must have been a considerable diffusion of unlabelled lactate from glycogen breakdown in inactive muscle fibres to adjacent active muscle fibres via the interstitial fluid that did not equilibrate with ¹⁴C lactate in the circulation. Received: 19 September 1997 / Received after revision: 15 December 1997 / Accepted: 22 January 1998     

Substrate utilization during prolonged exercise preceded by ingestion of13C-glucose in glycogen depleted and control subjects

The utilization of 100 g glucose by 5 control and 5 glycogen depleted subjects was investigated during a prolonged exercise, using naturally labelled¹³C-glucose as a metabolic tracer in conjunction with continuous respiratory exchange measurements. 1 h after glucose ingestion, the subjects pedaled for 2 h at 40% of theirVO₂ max. In both groups, expired CO₂ reached similar peaks of enrichment with¹³C after 75 min of exercise. At this time, control subjects used principally carbohydrate (65%), exogenous glucose representing 24% of the total energy expenditure. In contrast the glycogen depleted subjects used mainly lipid (70%), exogenous glucose representing 20% of the energy expenditure. In the latter subjects, FFA plasma levels remained 2 to 3 times higher than those of non-depleted subjects throughout the whole exercise period. Control subjects oxidized an average of 41±1 g and glycogen depleted subjects 38±2 g of exogenous glucose during the 2 h exercise period. It is concluded that during an exercise which is preceded by the ingestion of glucose:

1. The principal energetic substrate is carbohydrate for control and lipid for glycogen depleted subjects.
2. Inspite of their glycogen depletion, these subjects do not utilize ingested glucose to a greater extent than the control subjects, which is probably due to their higher FFA plasma levels.
3. The trend to store carbohydrate energy remains important during muscular exercise.

     

Reliability of a cycling time trial in a glycogen-depleted state

The aim of this study was to investigate the reliability of a protocol designed to simulate endurance performance in events of long duration (∼5 h) where endogenous carbohydrate stores are low. Seven male subjects were recruited (age 27 ± 7 years, VO_2max 66 ± 5 ml/kg/min, W _max 367 ± 42 W). The subjects underwent three trials to determine the reliability of the protocol. For each trial subjects entered the laboratory in the evening to undergo a glycogen-depleting exercise trial lasting approximately 2.5 h. The subjects returned the following morning in a fasted state to undertake a 1-h steady-state ride at 50% W _max followed by a time trial of approximately 40-min duration. Each trial was separated by 7–14 days. The trials were analysed for reliability of time to completion of the time trial using a coefficient of variation (CV), with 95% confidence intervals (data are mean ± SD). The times to complete the three trials were 2,546 ± 529, 2,585 ± 490 and 2,568 ± 555 s for trials 1, 2 and 3, respectively. The CV between trials 1 and 2 was 4.5% (95% CI 2.9–10.4%) and between trials 2 and 3, 3.8% (95% CI 2.4–9.9%). There was no difference in oxygen uptake, respiratory exchange ratio, carbohydrate oxidation, fat oxidation, plasma glucose concentration and plasma lactate concentration between the three trials. Therefore we can conclude that prior glycogen depletion does produce a reliable measure of performance with metabolic characteristics similar to ultraendurance exercise.     

Effect of low glycogen on glycogen synthase in human muscle during and after exercise

Subjects cycled at a work load calculated to elicit 75% of maximal oxygen uptake on two occasions: the first to fatigue (34.5 ± 5.3 min; mean ± SE), and the second at the same workload and for the same duration as the first. Biopsies were obtained from the quadriceps femoris muscle before and immediately after exercise, and 5 min post-exercise. Before the first experiment, muscle glycogen was lowered by a combination of exercise and diet, and before the second, experiment muscle glycogen was elevated. In the low glycogen condition (LG), muscle glycogen decreased from 169 ± 15 mmol glucosyl units kg^-1dry wt at to rest to 13 ± 6 after exercise. In the high glycogen condition (HG) glycogen decreased from 706 ± 52 at rest to 405 ± 68 after exercise. Glycogen synthase fractional activity (GSF) was always higher during the LG treatment. During exercise in the HG condition, those subjects who cycled for < 35 min (n= 3) had GSF values in muscle which were lower than at rest, whereas those subjects who cycled for > 35 min (n= 4) had values which were similar to or higher than at rest. Thus the change in GSF in muscle during HG was positively related to the exercise duration (r= 0.94; y = 254–17x + 0.3x²; P < 0.001) and negatively related to the glycogen content at the end of exercise (r=–0.82; y= 516–2x + 0.001x²; P < 0.05). During LG exercise GSF remained constant. GSF increased markedly after 5 min post-exercise in both HG and LG conditions. cAMP dependent protein kinase activity increased similarly during both LG and HG exercise and reverted to the preexercise values 5 min post-exercise. It is concluded that muscle contraction decreases GSF, but low glycogen levels can attenuate or abolish the decrease in GSF. The rapid increase of GSF during recovery from exercise does not require glycogen depletion during the exercise.     

Metabolic response to prolonged cycling with 13C-glucose ingestion following downhill running

The purpose of this study was to describe the effect of muscle damage and delayed-onset muscle soreness (DOMS) on the metabolic response during a subsequent period of prolonged concentric exercise (120 min, ~61% O_2max, on a cycle ergometer), with ingestion of 3 g of ¹³C-glucose/kg body mass. We hypothesized that the oxidation of plasma and exogenous glucose would be reduced, while the oxidation of glucose arising from muscle glycogen would be increased. Six male subjects were studied during exercise in a control situation and 2 days following downhill running, at a time when plasma creatine kinase (CK) activity was increased, and DOMS was present. Carbohydrate and lipid oxidation were computed from indirect respiratory calorimetry corrected for protein oxidation, while the oxidation of plasma glucose and muscle glycogen were computed from ¹³CO₂ and the ratio of ¹³C/¹²C in the plasma glucose. All data were presented as the mean and the standard error of the mean. The oxidation of protein (~6% energy yield, in the control and the experimental trial), lipid (~15 and ~18%), and carbohydrate (~79 and ~76%), as well as that of plasma glucose (~41 and ~46%), glucose from the liver (~12 and ~14%), and glucose from muscle glycogen (~38 and ~31%) were not significantly different between the control and experimental (DOMS) trials. The response of the plasma glucose, insulin, lactate, and free fatty acid concentrations was not modified by the previous eccentric exercise. These results indicate that the metabolic response to prolonged concentric exercise is not modified by muscle damage and DOMS resulting from a bout of eccentric exercise performed 2 days before.     

Brief intense exercise followed by passive recovery modifies the pattern of fuel use in humans during subsequent sustained intermittent exercise

The role of work period duration as the principal factor influencing carbohydrate metabolism during intermittent exercise has been investigated. Fuel oxidation rates and muscle glycogen and free carnitine content were compared between two protocols of sustained intermittent intense exercise with identical treadmill speed and total work duration. In the first experiment subjects (n=6) completed 40 min of intermittent treadmill running involving a work : recovery cycle of 6 : 9 s or 24 : 36 s on separate days. With 24 : 36 s exercise a higher rate of carbohydrate oxidation approached significance (P=0.057), whilst fat oxidation rate was lower (P ≤ 0.01) and plasma lactate concentration higher (P ≤ 0.01). Muscle glycogen was lower post‐exercise with 24 : 36 s (P ≤ 0.05). Muscle free carnitine decreased (P ≤ 0.05), but there was no difference between protocols. In the second experiment a separate group of subjects (n=5) repeated the intermittent exercise protocols with the addition of a 10‐min bout of intense exercise, followed by 43 ± 5 min passive recovery, prior to sustained (40 min) intermittent exercise. For this experiment the difference in fuel use observed previously between 6 : 9 s and 24 : 36 s was abolished. Carbohydrate and fat oxidation, plasma lactate and muscle glycogen levels were similar in 6 : 9 s and 24 : 36 s. When compared with the first experiment, this result was because of reduced carbohydrate oxidation in 24 : 36 s (P ≤ 0.05). There was no difference, and no change, in muscle free carnitine between protocols. A 10‐min bout of intense exercise, followed by 43 ± 5 min of passive recovery, substantially modifies fuel use during subsequent intermittent intense exercise.     

Effects of 3 days of carbohydrate supplementation on muscle glycogen content and utilisation during a 1-h cycling performance

This study compared the effects of supplementing the normal diets of six trained cyclists [maximal oxygen uptake $(\dot {V}$ O_2max) 4.5 (0.36)l · min^?1; values are mean (SD)] with additional carbohydrate (CHO) on muscle glycogen utilisation during a 1-h cycle time-trial (TT). Using a randomised crossover design, subjects consumed either their normal diet (NORM) for 3 days, which consisted of 426 (137) g · day^?1 CHO [5.9 (1.4) g · kg^?1 body mass (BM)], or additional CHO (SUPP) to increase their intake to 661 (76) g · day^?1 [9.3 (0.7) g · kg^?1 BM]. The SUPP diet elevated muscle glycogen content from 459?(83) to 565?(62) mmol?·?kg^?1 dry weight (d.w.) (P < 0.05). However, despite the increased pre-exercise muscle glycogen stores, there was no difference in the distance cycled during the TT [40.41 (1.44) vs 40.18 (1.76)?km for NORM and SUPP, respectively]. With NORM, muscle glycogen declined from 459 (83) to 175?(64) mmol?·?kg^?1 d.w., whereas with SUPP the corresponding values were 565?(62) and 292?(113) mmol?·?kg^?1 d.w. Accordingly, both muscle glycogen utilisation [277?(64) vs 273?(114) mmol?·?kg^?1 d.w.] and total CHO oxidation [169 (20) vs 165?(30)?g?·?h^?1 for NORM and SUPP, respectively] were similar. Neither were there any differences in plasma glucose or lactate concentrations during the two experimental trials. Plasma glucose concentration averaged 5.5 (0.5) and 5.6 (0.6) mmol?·?l^?1, while plasma lactate concentration averaged 4.4 (1.9) and 4.4 (2.3) mmol?·?l^?1 for NORM and SUPP, respectively. The results of this study show that when well-trained subjects increase the CHO content of their diet for 3 days from 6 to 9 g?·?kg^?1 BM there is only a modest increase in muscle glycogen content. Since supplementary CHO did not improve TT performance, we conclude that additional CHO provides no benefit to performance for athletes who compete in intense, continuous events lasting 1?h. Furthermore, the substantial muscle CHO reserves observed at the termination of exercise indicate that whole-muscle glycogen depletion does not determine fatigue at this exercise intensity and duration.     

High-intensity exercise and muscle glycogen availability in humans

This study investigated the effects of muscle glycogen availability on performance and selected physiological and metabolic responses during high-intensity intermittent exercise. Seven male subjects completed a regimen of exercise and dietary intake (48 h) to either lower and keep low (LOW-CHO) or lower and then increase (HIGH-CHO) muscle glycogen stores, on two separate occasions at least a week apart. On each occasion the subjects completed a short-term (<10 min) and prolonged (>30 min) intermittent exercise (IEX) protocol, 24 h apart, which consisted of 6-s bouts of high-intensity exercise performed at 30-s intervals on a cycle ergometer. Glycogen concentration (mean ± SEM) in m. vastus lateralis before both IEx_short and IEx_long was significantly lower following LOW-CHO [180 (14), 181 (17) mmol kg (dw)^–1] compared with HIGH-CHO [397 (35), 540 (25) mmol kg (dw)^–1]. In both IEx_short and IEx_long, significantly less work was performed following LOW-CHO compared with HIGH-CHO. In IEx_long, the number of exercise bouts that could be completed at a pre-determined target exercise intensity increased by 265% from 111 (14) following LOW-CHO to 294 (29) following HIGH-CHO (P < 0.05). At the point of fatigue in IEx_long, glycogen concentration was significantly lower with the LOW-CHO compared with HIGH-CHO [58 (25) vs. 181 (46) mmol kg (dw)^–1, respectively]. The plasma concentrations of adrenaline and nor-adrenaline (in IEx_short and IEx_long), and FFA and glycerol (in IEx_long), increased several-fold above resting values with both experimental conditions. Oxygen uptake during the exercise periods in IEx_long approached 70% of V o_2max. These results suggest that muscle glycogen availability can affect performance during both short-term and more prolonged high-intensity intermittent exercise and that with repeated exercise periods as short as 6 s, there can be a relatively high aerobic contribution.     

Effect of a 20-day ski trek on fuel selection during prolonged exercise at low workload with ingestion of <Superscript>13</Superscript>C-glucose

Fuel selection was measured in five subjects (36.0 ± 10.5 years old; 87.3 ± 12.5 kg; mean ± SD) during a 120-min tethered walking with ski poles (1.12 l O₂ min⁻¹) with ingestion of ¹³C-glucose (1.5 g kg⁻¹), before and after a 20-day 415-km ski trek [physical activity level (PAL) ~3], using respiratory calorimetry, urea excretion, and ¹³C/¹²C in expired CO₂ and in plasma glucose. Before the ski trek, protein oxidation contributed 9.7 ± 1.6% to the energy yield (%En) while fat and carbohydrate (CHO) oxidation provided 73.5 ± 5.5 and 16.7 ± 6.5%En. Plasma glucose was the main source of CHO (52.9 ± 9.5%En) with similar contributions from exogenous glucose (27.2 ± 3.1%En), glucose from the liver (25.6 ± 8.3%En) and muscle glycogen (20.9 ± 4.0%En). Endogenous CHO contributed 46.6 ± 3.9%En. Following the ski trek %En from protein, fat, CHO, exogenous glucose and endogenous CHO were not significantly modified (10.1 ± 1.3, 15.8 ± 6.7, 74.1 ± 6.5, 28.7 ± 3.0 and 45.5 ± 7.5%En, respectively) but the %En from plasma glucose and glucose from the liver (41.1 ± 3.6 and 12.4 ± 4.0%En) were reduced, while that from muscle glycogen increased (33.0 ± 4.5%En). These results show that in subjects in the fed state with glucose ingestion during exercise, CHO is the main substrate oxidized, with major contributions from both exogenous and endogenous CHO. Following a ~3-week period of prolonged low intensity exercise, the %En from protein, fat, CHO, exogenous glucose and endogenous CHO were not modified. However, the %En from glucose released from the liver was reduced (possibly due to an increased insulin sensitivity of the liver) while that from muscle glycogen was increased. Ethical standards: the experiments reported in this study comply with the current laws of Canada.     

Glycogen breakdown in different human muscle fibre types during exhaustive exercise of short duration

The rates of glycogen breakdown during exhaustive intense exercise of three different intensities were determined in type I and subgroups of type II fibres. The exercise intensity corresponded to 122 ± 2 , 150 ± 7 and 194 ± 7% of Vo_2max. Muscle biopsies were taken from both legs before and immediately after exhaustion. Muscle lactate concentration increased by 27 ± 1 , 27 ± 1 and 20 ± 2 mmolkg^-1 wet wt during the exercise at 122 , 150 and 194%Vo_2max, respectively. The rates of glycogen depletion increased in all fibre types with increasing intensity, and the decline in type I fibres was 30–35% less than in type II fibres at all intensities. No differences were observed between the glycogen depletion rates in subgroups of type II fibres (IIA, IIAB and IIB). During the exercise at 194% Vo_2max, the rates of glycogen breakdown were 0.35 ± 0.03 and 0.52 ± 0.05 mmol s^-1 kg^-1 wet wt in type I and type II fibres, respectively. For both fibre types, the rates were 32 and 69% lower during the exercise at 150 and 12296 VO_2max. These data indicate that the glycolytic capacity of type I fibres is 30–35% lower than the capacity of type II fibres, in good agreement with the differences in phosphorylase and phosphofructokinase activities (Essén et al. 1 975 , Harris et al. 1976). The data also indicate that both fibre types contribute significantly to the anaerobic energy release at powers up till almost 200%Vo_2max.     

Carbohydrate feeding and glycogen synthesis during exercise in man

In 7 male cyclists glycogen synthesis during exercise and rest was studied. Each subject did two exercise trials (A and B), in random order. In both trials, after determining the maximal workload (W _max), intermittent exercise was given to exhaustion. After the exhaustive exercise and taking a muscle biopsy the subjects either exercised at 40%W _max for 3 h (trial A) or rested for 3 h (trial B), during which they consumed approximately 21 of a 25% malto-dextrine drink in both trials. After 3 h rest (trial A) or 3 h of mild exercise (trial B) a second muscle biopsy was taken for total glycogen and histochemistry (ATPase and PAS). Blood glucose and insulin levels were elevated during the first 2 h of exercise (p<0.05). Glycogen depletion was most pronounced in type I and to a less extent in type IIA fibers. In trial A muscle glycogen increased from 136±66 to 199±71 mmol/kg DW, and in trial B from 145±56 to 257±79 mmol/kg DW. During exercise glycogen repletion was restricted to type IIA and IIB fibers, whereas during rest glycogen synthesis occurred both in type I and type II fibers. The present study demonstrates that oral carbohydrate administered during exercise may not only provide substrate for energy metabolism, but can also be utilized for glycogen synthesis in the non-active muscle fibers.     

13C MRS reveals a small diurnal variation in the glycogen content of human thigh muscle

There is marked diurnal variation in the glycogen content of skeletal muscles of animals, but few studies have addressed such variations in human muscles. ¹³C MRS can be used to noninvasively measure the glycogen content of human skeletal muscle, but no study has explored the diurnal variations in this parameter. This study aimed to investigate whether a diurnal variation in glycogen content occurs in human muscles and, if so, to what extent it can be identified using ¹³C MRS. Six male volunteers were instructed to maintain their normal diet and not to perform strenuous exercise for at least 3 days before and during the experiment. Muscle glycogen and blood glucose concentrations were measured six times in 24 h under normal conditions in these subjects. The glycogen content in the thigh muscle was determined noninvasively by natural abundance ¹³C MRS using a clinical MR system at 3 T. Nutritional analysis revealed that the subjects' mean carbohydrate intake was 463 ± 137 g, being approximately 6.8 ± 2.4 g/kg body weight. The average sleeping time was 5.9 ± 1.0 h. The glycogen content in the thigh muscle at the starting point was 64.8 ± 20.6 mM. Although absolute and relative individual variations in muscle glycogen content were 7.0 ± 2.1 mM and 11.3 ± 4.6%, respectively, no significant difference in glycogen content was observed among the different time points. This study demonstrates that normal food intake (not fat and/or carbohydrate rich), sleep and other daily activities have a negligible influence on thigh muscle glycogen content, and that the diurnal variation of the glycogen content in human muscles is markedly smaller than that in animal muscles. Moreover, the present results also support the reproducibility and availability of ¹³C MRS for the evaluation of the glycogen content in human muscles. Copyright © 2015 John Wiley & Sons, Ltd.     

Noninvasive assessment of in vivo glycogen kinetics in humans: effect of increased physical activity on glycogen breakdown and synthesis

In vivo glycogen kinetics was estimated with the simultaneous use of indirect calorimetry and tracer technology in healthy humans during 24-h periods with low or moderate physical activity (1 or 3 exercise sessions each day). Two ¹³C-carbohydrates meals were administered at 9.30 a.m. and 1.30 p.m., and one ¹²C-carbohydrates meal at 6.30 p.m. Net carbohydrate oxidation (net CHO ox) was measured over a 24 h period by indirect calorimetry and oxidation of ¹³C-labelled carbohydrates (13C CHO ox) was estimated from ¹³CO₂ production. Glycogen breakdown, assessed for the period 8.15 a.m.-6.30 p.m. as the difference between net CHO ox and ¹³C CHO ox, was increased 1.6 times with three exercise sessions [123.3 (SEM 8.0) g] versus one session [77.9 (SEM 7.7) g, P<0.0001]. Carbohydrate balances over 24 h were close to zero under both conditions, indicating that glycogen breakdown was matched by an equivalent glycogen synthesis. It was concluded that simultaneous use of indirect calorimetry and tracer technology may make possible the estimation of glycogen kinetics in humans. Moderate physical activity enhanced both glycogen breakdown and synthesis. This stimulation of glycogen metabolism may therefore play a role in the enhanced insulin sensitivity induced by physical exercise.     

Exercise with low glycogen increases PGC-1α gene expression in human skeletal muscle

Recent studies suggest that carbohydrate restriction can improve the training-induced adaptation of muscle oxidative capacity. However, the importance of low muscle glycogen on the molecular signaling of mitochondrial biogenesis remains unclear. Here, we compare the effects of exercise with low (LG) and normal (NG) glycogen on different molecular factors involved in the regulation of mitochondrial biogenesis. Ten highly trained cyclists (VO_2max 65 ± 1 ml/kg/min, W _max 387 ± 8 W) exercised for 60 min at approximately 64 % VO_2max with either low [166 ± 21 mmol/kg dry weight (dw)] or normal (478 ± 33 mmol/kg dw) muscle glycogen levels achieved by prior exercise/diet intervention. Muscle biopsies were taken before, and 3 h after, exercise. The mRNA of peroxisome proliferator-activated receptor-γ coactivator-1 was enhanced to a greater extent when exercise was performed with low compared with normal glycogen levels (8.1-fold vs. 2.5-fold increase). Cytochrome c oxidase subunit I and pyruvate dehydrogenase kinase isozyme 4 mRNA were increased after LG (1.3- and 114-fold increase, respectively), but not after NG. Phosphorylation of AMP-activated protein kinase, p38 mitogen-activated protein kinases and acetyl-CoA carboxylase was not changed 3 h post-exercise. Mitochondrial reactive oxygen species production and glutathione oxidative status tended to be reduced 3 h post-exercise. We conclude that exercise with low glycogen levels amplifies the expression of the major genetic marker for mitochondrial biogenesis in highly trained cyclists. The results suggest that low glycogen exercise may be beneficial for improving muscle oxidative capacity.     

Post-exercise ketosis and the glycogen content of liver and muscle in rats on a high carbohydrate diet

Summary Post-exercise ketosis is known to be suppressed by physical training and by a high carbohydrate diet. As a result it has often been presumed, but not proven, that the development of post-exercise ketosis is closely related to the glycogen content of the liver. We therefore studied the effect of 1 h of treadmill running on the blood 3-hydroxybutyrate and liver and muscle glycogen concentrations of carbohydrate-loaded trained (n=72) and untrained rats (n=72). Resting liver and muscle glycogen levels were 25%–30% higher in the trained than in the untrained animals. The resting 3-hydroxybutyrate concentrations of both groups of rats were very low: <0.08 mmol·1⁻¹. Exercise did not significantly influence the blood 3-hydroxybutyrate concentrations of trained rats, but caused a marked post-exercise ketosis (1.40±0.40 mmol·1⁻¹ 1 h after exercise) in the untrained animals, the time-course of which was the approximate inverse of the changes in liver glycogen concentration. Interpreting the results in the light of similar data obtained after a normal and low carbohydrate diet it has been concluded that trained animals probably owe their relative resistance to post-exercise ketosis to their higher liver glycogen concentrations as well as to greater peripheral stores of mobilizable carbohydrate.     

Intramyocellular lipid stores increase markedly in athletes after 1.5 days lipid supplementation and are utilized during exercise in proportion to their content

Intramyocellular lipids (IMCL) and muscle glycogen provide local energy during exercise (EX). The objective of this study was to clarify the role of high versus low IMCL levels at equal initial muscle glycogen on fuel selection during EX. After 3 h of depleting exercise, 11 endurance-trained males consumed in a crossover design a high-carbohydrate (7 g kg⁻¹ day⁻¹) low-fat (0.5 g kg⁻¹ day⁻¹) diet (HC) for 2.5 days or the same diet with 3 g kg⁻¹ day⁻¹ more fat provided during the last 1.5 days of diet (four meals; HCF). Respiratory exchange, thigh muscle substrate breakdown by magnetic resonance spectroscopy, and plasma FFA oxidation ([1-¹³C]palmitate) were measured during EX (3 h, 50% W _max). Pre-EX IMCL concentrations were 55% higher after HCF. IMCL utilization during EX in HCF was threefold greater compared with HC (P < 0.001) and was correlated with aerobic power and highly correlated (P < 0.001) with initial content. Glycogen values and decrements during EX were similar. Whole-body fat oxidation (Fat_ox) was similar overall and plasma FFA oxidation smaller (P < 0.05) during the first EX hour after HCF. Myocellular fuels contributed 8% more to whole-body energy demands after HCF (P < 0.05) due to IMCL breakdown (27% Fat_ox). After EX, when both IMCL and glycogen concentrations were again similar across trials, a simulated 20-km time-trial showed no difference in performance between diets. In conclusion, IMCL concentrations can be increased during a glycogen loading diet by consuming additional fat for the last 1.5 days. During subsequent exercise, IMCL decrease in proportion to their initial content, partly in exchange for peripheral fatty acids.     

Improved glucose tolerance after intensive life style intervention occurs without changes in muscle ceramide or triacylglycerol in morbidly obese subjects

Aim: This study investigated the effect of a 15‐week life style intervention (hypocaloric diet and regular exercise) on glucose tolerance, skeletal muscle lipids and muscle metabolic adaptations in 14 female and 9 male morbidly obese subjects (age: 32.5 ± 2.3 years, body mass index: 46.1 ± 1.9 kg m^?2). Method: Before and after the life style intervention, an oral glucose tolerance test was performed and a muscle biopsy was obtained in the fasted state. Maximal oxygen uptake was measured by an indirect test. Results: After the intervention, body weight was decreased (P < 0.05) by 11 ± 1%, maximal oxygen uptake increased (P < 0.05) by 18 ± 5% and glucose tolerance increased (P < 0.05) by 12 ± 3%. Muscle glycogen was significantly increased by 47 ± 14%, but muscle ceramide and triacylglycerol content remained completely unchanged. No sex difference was observed for any of these parameters, but during submaximal exercise a marked decrease (P < 0.05) of 15 ± 2% in respiratory exchange ratio was seen only in females indicating an enhanced fat oxidation. Conclusion: Despite a marked weight loss and an improved aerobic capacity muscle ceramide and triacylglycerol remained unchanged after intensive life style intervention, and muscle lipids hence do not seem to play a major role for the improved glucose tolerance in these morbidly obese subjects. Interestingly, only the females improved fat oxidation during submaximal exercise after the intervention implying the presence of a sex‐dependent response to intensive life style adaptation.     

Intramyocellular lipid and glycogen content are reduced following resistance exercise in untrained healthy males

Resistance exercise has recently been shown to improve whole-body insulin sensitivity in healthy males. Whether this is accompanied by an exercise-induced decline in skeletal muscle glycogen and/or lipid content remains to be established. In the present study, we determined fibre-type-specific changes in skeletal muscle substrate content following a single resistance exercise session. After an overnight fast, eight untrained healthy lean males participated in a ~45 min resistance exercise session. Muscle biopsies were collected before, following cessation of exercise, and after 30 and 120 min of post-exercise recovery. Subjects remained fasted throughout the test. Conventional light and (immuno)fluorescence microscopy were applied to assess fibre-type-specific changes in intramyocellular triacylglycerol (IMTG) and glycogen content. A significant 27±7% net decline in IMTG content was observed in the type I muscle fibres (P<0.05), with no net changes in the type IIa and IIx fibres. Muscle glycogen content decreased with 23±6, 40±7 and 44±7% in the type I, IIa and IIx muscle fibres, respectively (P<0.05). Fibre-type-specific changes in intramyocellular lipid and/or glycogen content correlated well with muscle fibre-type oxidative capacity. During post-exercise recovery, type I muscle fibre lipid content returned to pre-exercise levels within 120 min. No changes in muscle glycogen content were observed during recovery. We conclude that intramyocellular lipid and glycogen stores are readily used during resistance exercise and this is likely associated with the reported increase in whole-body insulin sensitivity following resistance exercise.