Mitochondrial lipid oxidation is impaired in cultured myotubes from obese humans.

OBJECTIVE: The skeletal muscle of obese humans is characterized by an inability to appropriately respond to alterations in substrate availability. The purpose of this study was to determine if this metabolic inflexibility with obesity is retained in mitochondria of human skeletal muscle cells raised in culture (HSkMC) and to identify potential mechanisms involved. DESIGN: Mitochondrial respiration was measured in permeabilized myotubes cultured from lean and obese individuals before and after a 24-h lipid incubation. RESULTS: Mitochondrial respiration (state 3) in the presence of lipid substrate (palmitoyl carnitine) increased by almost twofold after lipid incubation in HSkMC from lean, but not obese subjects, indicative of metabolic inflexibility with obesity. The 24-h lipid incubation increased mitochondrial DNA (mtDNA) copy number in HSkMC from lean subjects by +16% (P<0.05); conversely, mtDNA copy number decreased in myotubes cultured from obese individuals (-13%, P=0.06). When respiration data were normalized to mtDNA copy number and other indices of mitochondrial content (COX-IV protein content and CS activity), the significant treatment effects of lipid incubation persisted in the lean subjects, suggesting concomitant alterations in mitochondrial function; no similar adjustment was evident in HSkMC from obese individuals. CONCLUSION: These data indicate that the skeletal muscle of obese individuals inherently lacks metabolic flexibility in response to lipid exposure, which consists of an inability to increase mitochondrial respiration in the presence of lipid substrate and perhaps by an inability to induce mitochondrial proliferation.

Transcriptional activation of the IL-6 gene in human contracting skeletal muscle: influence of muscle glycogen content.

In humans, the plasma interleukin 6 (IL-6) concentration increases dramatically during low-intensity exercise. Measurements across the working limb indicate that skeletal muscle is the source of IL-6 production. To determine whether energy availability influences the regulation of IL-6 expression during prolonged exercise, six male subjects completed two trials consisting of 180 min of two-legged dynamic knee extensor with either normal or low (~60% of control) pre-exercise muscle glycogen levels. Increases in plasma IL-6 during exercise were significantly higher (P<0.05) in the low-glycogen (16-fold) trial verses the control (10-fold) trial. Transcriptional activation of the IL-6 gene in skeletal muscle was also higher in the low-glycogen trial; it increased by about 40-fold after 90 min of exercise and about 60-fold after 180 min of exercise. Muscle IL-6 mRNA followed a similar but delayed pattern, increasing by more than 100-fold in the low-glycogen trial and by about 30-fold in the control trial. These data demonstrate that exercise activates transcription of the IL-6 gene in working skeletal muscle, a response that is dramatically enhanced when glycogen levels are low. These findings also support the hypothesis that IL-6 may be produced by contracting myofibers when glycogen levels become critically low as a means of signaling the liver to increase glucose production.

δ-Catenin, a Wnt/ß-catenin modulator, reveals inducible mutagenesis promoting cancer cell survival adaptation and metabolic reprogramming.

Mutations of Wnt/ß-catenin signaling pathway has essential roles in development and cancer. Although ß-catenin and adenomatous polyposis coli (APC) gene mutations are well established and are known to drive tumorigenesis, discoveries of mutations in other components of the pathway lagged, which hinders the understanding of cancer mechanisms. Here we report that δ-catenin (gene designation: CTNND2), a primarily neural member of the ß-catenin superfamily that promotes canonical Wnt/ß-catenin/LEF-1-mediated transcription, displays exonic mutations in human prostate cancer and promotes cancer cell survival adaptation and metabolic reprogramming. When overexpressed in cells derived from prostate tumor xenografts, δ-catenin gene invariably gives rise to mutations, leading to sequence disruptions predicting functional alterations. Ectopic δ-catenin gene integrating into host chromosomes is locus nonselective. δ-Catenin mutations promote tumor development in mouse prostate with probasin promoter (ARR2PB)-driven, prostate-specific expression of Myc oncogene, whereas mutant cells empower survival advantage upon overgrowth and glucose deprivation. Reprogramming energy utilization accompanies the downregulation of glucose transporter-1 and poly (ADP-ribose) polymerase cleavage while preserving tumor type 2 pyruvate kinase expression. δ-Catenin mutations increase ß-catenin translocation to the nucleus and hypoxia-inducible factor 1α (HIF-1α) expression. Therefore, introducing δ-catenin mutations is an important milestone in prostate cancer metabolic adaptation by modulating ß-catenin and HIF-1α signaling under glucose shortage to amplify its tumor-promoting potential.

Influence of skeletal muscle glycogen on passive rewarming after hypothermia.

To examine the influence of muscle glycogen on the thermal responses to passive rewarming subsequent to mild hypothermia, eight subjects completed two cold-water immersions (18 degrees C), followed by 75 min of passive rewarming (24 degrees C air, resting in blanket). The experiments followed several days of different exercise-diet regimens eliciting either low (LMG; 141.0 +/- 10.5 mmol.kg.dry wt-1) or normal (NMG; 526.2 +/- 44.2 mmol.kg.dry wt-1) prewarming muscle glycogen levels. Cold-water immersion was performed for 180 min or to a rectal temperature (Tre) of 35.5 degrees C. In four subjects (group A, body fat = 20 +/- 1%), postimmersion Tre was similar to preimmersion Tre for both trials (36.73 +/- 0.18 vs. 37.26 +/- 0.18 degrees C, respectively). Passive rewarming in group A resulted in an increase in Tre of only 0.13 +/- 0.08 degrees C. Conversely, initial rewarming Tre for the other four subjects (group B, body fat = 12 +/- 1%) averaged 35.50 +/- 0.05 degrees C for both trials. Rewarming increased Tre similarly in group B during both LMG (0.76 +/- 0.25 degrees C) and NMG (0.89 +/- 0.13 degrees C). Afterdrop responses, evident only in those individuals whose body core cooled during immersion (group B), were not different between LMG and NMG. These data support the contention that Tre responses during passive rewarming are related to body insulation. Furthermore these results indicate that low muscle glycogen levels do not impair rewarming time nor alter after-drop responses during passive rewarming after mild-to-moderate hypothermia.

Chronic contractile activity upregulates the proteasome system in rabbit skeletal muscle.

Remodeling of skeletal muscle in response to altered patterns of contractile activity is achieved, in part, by the regulated degradation of cellular proteins. The ubiquitin-proteasome system is a dominant pathway for protein degradation in eukaryotic cells. To test the role of this pathway in contraction-induced remodeling of skeletal muscle, we used a well-established model of continuous motor nerve stimulation to activate tibialis anterior (TA) muscles of New Zealand White rabbits for periods up to 28 days. Western blot analysis revealed marked and coordinated increases in protein levels of the 20S proteasome and two of its regulatory proteins, PA700 and PA28. mRNA of a representative proteasome subunit also increased coordinately in contracting muscles. Chronic contractile activity of TA also increased total proteasome activity in extracts, as measured by the hydrolysis of a proteasome-specific peptide substrate, and the total capacity of the ubiquitin-proteasome pathway, as measured by the ATP-dependent hydrolysis of an exogenous protein substrate. These results support the potential role of the ubiquitin-proteasome pathway of protein degradation in the contraction-induced remodeling of skeletal muscle.

Training cessation does not alter GLUT-4 protein levels in human skeletal muscle.

The purpose of this study was to determine whether short-term training cessation resulted in reduced GLUT-4 protein levels. Endurance- (n = 12, ET) and strength-trained (n = 12) individuals (ST) were examined before and after 14 days of training withdrawal. GLUT-4 content was determined from muscle biopsy samples of the gastrocnemius in ET and the vastus lateralis in ST. Insulin sensitivity (oral glucose tolerance test) was significantly (P < 0.05) reduced in ET and ST with training cessation. GLUT-4 content was unaltered (P > 0.05) in both groups (92 and 100% of trained values for ET and ST, respectively). In ET, citrate synthase activity decreased significantly (P < 0.05) with training withdrawal (41.0 +/- 3.6 vs. 30.6 +/- 2.8 mumol.g-1.min-1); in ST no change was evident. The decrement in insulin sensitivity with the cessation of endurance- or resistance-oriented activity is therefore not associated with a reduction in GLUT-4 protein content. Muscle oxidative capacity and GLUT-4 content do not coincide with the removal of endurance training.

Hypohydration does not impair skeletal muscle glycogen resynthesis after exercise.

The purpose of this investigation was to examine the effects of moderate hypohydration (HY) on skeletal muscle glycogen resynthesis after exhaustive exercise. On two occasions, eight males completed 2 h of intermittent cycle ergometer exercise (4 bouts of 17 min at 60% and 3 min at 80% of maximal O2 consumption/10 min rest) to reduce muscle glycogen concentrations (control values 711 +/- 41 mumol/g dry wt). During one trial, cycle exercise was followed by several hours of light upper body exercise in the heat without fluid replacement to induce HY (-5% body wt); in the second trial, sufficient water was ingested during the upper body exercise and heat exposure to maintain euhydration (EU). In both trials, 400 g of carbohydrate were ingested at the completion of exercise and followed by 15 h of rest while the desired hydration level was maintained. Muscle biopsy samples were obtained from the vastus lateralis immediately after intermittent cycle exercise (T1) and after 15 h of rest (T2). During the HY trial, the muscle water content was lower (P less than 0.05) at T1 and T2 (288 +/- 9 and 265 +/- 5 ml/100 g dry wt, respectively; NS) than during EU (313 +/- 8 and 301 +/- 4 ml/100 g dry wt, respectively; NS). Muscle glycogen concentration was not significantly different during EU and HY at T1 (200 +/- 35 vs. 251 +/- 50 mumol/g dry wt) or T2 (452 +/- 34 vs. 491 +/- 35 mumol/g dry wt). These data indicate that, despite reduced water content during the first 15 h after heavy exercise, skeletal muscle glycogen resynthesis is not impaired.

Improvements in exercise performance: effects of carbohydrate feedings and diet.

In an effort to determine the effects of carbohydrate (CHO) feedings immediately before exercise in both the fasted and fed state, 10 well-trained male cyclists [maximum O2 consumption (VO2 max), 4.35 +/- 0.11 l/min)] performed 45 min of cycling at 77% VO2 max followed by a 15-min performance ride on an isokinetic cycle ergometer. After a 12-h fast, subjects ingested 45 g of liquid carbohydrate (LCHO), solid carbohydrate confectionery bar (SCHO), or placebo (P) 5 min before exercise. An additional trial was performed in which a high-CHO meal (200 g) taken 4 h before exercise was combined with a confectionery bar feeding (M + SCHO) immediately before the activity. At 10 min of exercise, serum glucose values were elevated by 18 and 24% during SCHO and LCHO, respectively, compared with P. At 0 and 45 min no significant differences were observed in muscle glycogen concentration or total use between the four trials. Total work produced during the final 15 min of exercise was significantly greater (P less than 0.05) during M + SCHO (194,735 +/- 9,448 N X m), compared with all other trials and significantly greater (P less than 0.05) during LCHO and SCHO (175,204 +/- 11,780 and 176,013 +/- 10,465 N X m, respectively) than trial P (159,143 +/- 11,407 N X m). These results suggest that, under conditions when CHO stores are less than optimal, exercise performance is enhanced with the ingestion of 45 g of CHO 5 min before 1 h of intense cycling.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of thermal factors on aerobic capacity improvements with endurance training.

This investigation studied the importance of the rise in body temperature during exercise for aerobic capacity adaptations produced by endurance training. The approach used was to compare training effects produced by subjects exercising in hot (35 degrees C) water vs. cold (20 degrees C) water. Hot water was used to potentiate, and cold water to blunt, the rise in body temperature during exercise. Eighteen young men trained by cycle-ergometer exercise at 60% of maximal oxygen uptake (VO2max) while immersed to the neck in either hot (HWT, n = 9) or cold (CWT, n = 9) water for 60 min, 5 days/wk, for 8 wk. Before and after training, VO2max, erythrocyte volume, plasma volume, and vastus lateralis citrate synthase activity were measured. Training increased (P < 0.01) VO2max by 13%, with no difference between HWT and CWT in the magnitude of the effect. Erythrocyte volume increased 4% (P < 0.01) with training, with no difference between HWT and CWT in the magnitude of the effect. Plasma volume remained unchanged by training in both the HWT and CWT groups. Last, vastus lateralis citrate synthase activity increased by 38% with training, but there was no difference between HWT and CWT in the training effect. Thus, exercise-induced body temperature elevations are not an important stimulus for the aerobic adaptations to moderate-intensity endurance training.

Human tolerance to heat strain during exercise: influence of hydration.

This study determined whether 1) exhaustion from heat strain occurs at the same body temperatures during exercise in the heat when subjects are euhydrated as when they are hypohydrated, 2) aerobic fitness influences the body temperature at which exhaustion from heat strain occurs, and 3) curves could be developed to estimate exhaustion rates at a given level of physiological strain. Seventeen heat-acclimated men [maximal oxygen uptake (VO2max) from 45 to 65 ml.kg-1.min-1] attempted two heat stress tests (HSTs): one when euhydrated and one when hypohydrated by 8% of total body water. The HSTs consisted of 180 min of rest and treadmill walking (45% VO2max) in a hot-dry (ambient temperature 49 degrees C, relative humidity 20%) environment. The required evaporative cooling (Ereq) exceeded the maximal evaporative cooling capacity of the environment (Emax); thus thermal equilibrium could not be achieved and 27 of 34 HSTs ended by exhaustion from heat strain. Our findings concerning exhaustion from heat strain are 1) hypohydration reduced the core temperature that could be tolerated; 2) aerobic fitness, per se, did not influence the magnitude of heat strain that could be tolerated; 3) curves can be developed to estimate exhaustion rates for a given level of physiological strain; and 4) exhaustion was rarely associated with a core temperature up to 38 degrees C, and it always occurred before a temperature of 40 degrees C was achieved. These findings are applicable to heat-acclimated individuals performing moderate-intensity exercise under conditions where Ereq approximates or exceeds Emax and who have high skin temperatures.

Thermoregulation during cold water immersion is unimpaired by low muscle glycogen levels.

This investigation studied the importance of muscle glycogen levels for body temperature regulation during cold stress. Physiological responses of eight euglycemic males were measured while they rested in cold (18 degrees C, stirred) water on two separate occasions. The trials followed a 3-day program of diet and exercise manipulation designed to produce either high (HMG) or low (LMG) preimmersion glycogen levels in the muscles of the legs, arms, and upper torso. Preimmersion vastus lateralis muscle glycogen concentrations were lower during the LMG trial (144 +/- 14 mmol glucose/kg dry tissue) than the HMG trial (543 +/- 53 mmol glucose/kg dry tissue). There were no significant differences between the two trials in shivering as reflected by aerobic metabolic rate or in the amount of body cooling as reflected by changes in rectal temperature during the immersions. Postimmersion muscle glycogen levels remained unchanged from preimmersion levels in both trials. Small but significant increases in plasma glucose and lactate concentration occurred during both immersions. Plasma glycerol increased during immersion in the LMG trial but not in the HMG trial. Plasma free fatty acid concentration increased during both immersion trials, but the change was apparent sooner in the LMG immersion. It was concluded that thermoregulatory responses of moderately lean and fatter individuals exposed to cold stress were not impaired by a substantial reduction in the muscle glycogen levels of several major skeletal muscle groups. Furthermore, the data suggest that, depending on the intensity of shivering, other metabolic substrates are available to enable muscle glycogen to be spared.

The effect of detraining and reduced training on the physiological adaptations to aerobic exercise training.

In previously sedentary individuals, regularly performed aerobic exercise results in significant improvements in exercise capacity. The development of peak exercise performance, as typified by competitive endurance athletes, is dependent upon several months to years of aerobic training. The physiological adaptations associated with these improvements in both maximal exercise performance, as reflected by increases in maximal oxygen uptake (VO2max), and submaximal exercise endurance include increases in both cardiovascular function and skeletal muscle oxidative capacity. Despite prolonged periods of aerobic training, reductions in maximal and submaximal exercise performance occur within weeks after the cessation of training. These losses in exercise performance coincide with declines in cardiovascular function and muscle metabolic potential. Significant reductions in VO2max have been reported to occur within 2 to 4 weeks of detraining. This initial rapid decline in VO2max is likely related to a corresponding fall in maximal cardiac output which, in turn, appears to be mediated by a reduced stroke volume with little or no change in maximal heart rate. A loss in blood volume appears to, at least partially, account for the decline in stroke volume and VO2max during the initial weeks of detraining, although changes in cardiac hypertrophy, total haemoglobin content, skeletal muscle capillarisation and temperature regulation have been suggested as possible mediating factors. When detraining continues beyond 2 to 4 weeks, further declines in VO2max appear to be a function of corresponding reductions in maximal arterial-venous (mixed) oxygen difference. Whether reductions in oxygen delivery to and/or extraction by working muscle regulates this progressive decline is not readily apparent. Changes in maximal oxygen delivery may result from decreases in total haemoglobin content and/or maximal muscle blood flow and vascular conductance. The declines in skeletal muscle oxidative enzyme activity observed with detraining are not causally linked to changes in VO2max but appear to be functionally related to the accelerated carbohydrate oxidation and lactate production observed during exercise at a given intensity. Alternatively, reductions in submaximal exercise performance may be related to changes in the mean transit time of blood flow through the active muscle and/or the thermoregulatory response (i.e. degree of thermal strain) to exercise. In contrast to the responses observed with detraining, currently available research indicates that the adaptations to aerobic training may be retained for at least several months when training is maintained at a reduced level. Reductions of one- to two-thirds in training frequency and/or duration do not significantly alter VO2max or submaximal endurance time provided the intensity of each exercise session is maintained.(ABSTRACT TRUNCATED AT 400 WORDS)

Regulation of glycogen resynthesis following exercise. Dietary considerations.

With the cessation of exercise, glycogen repletion begins to take place rapidly in skeletal muscle and can result in glycogen levels higher than those present before exercise. Understanding the rate-limiting steps that regulate glycogen synthesis will provide us with strategies to increase the resynthesis of glycogen during recovery from exercise, and thus improve performance. Given the importance of muscle glycogen to endurance performance, various factors which may optimise glycogen resynthesis rate and insure complete restoration have been of interest to both the scientist and athlete. The time required for complete muscle glycogen resynthesis after prolonged moderate intensity exercise is generally considered to be 24 hours provided approximately 500 to 700g of carbohydrate is ingested. Muscle glycogen synthesis rate is highest during the first 2 hours after exercise. Ingestion of 0.70g glucose/kg bodyweight every 2 hours appears to maximise glycogen resynthesis rate at approximately 5 to 6 mumol/g wet weight/h during the first 4 to 6 hours after exhaustive exercise. Further enhancement of glycogen resynthesis rate with ingestion of greater than 0.70g glucose/kg bodyweight appears to be limited by the constraints imposed by gastric emptying. Ingestion of glucose or sucrose results in similar muscle glycogen resynthesis rates while glycogen synthesis in liver is better served with the ingestion of fructose. Also, increases in muscle glycogen content during the first 4 to 6 hours after exercise are greater with ingestion of simple as compared with complex carbohydrate. Glycogen synthase activity is a key component in the regulation of glycogen resynthesis. Glycogen synthase enzyme exists in 2 states: the less active, more phosphorylated (D) form which is under allosteric control of glucose-6-phosphate, and the more active, less phosphorylated (I) form which is independent of glucose-6-phosphate. There is generally an inverse relationship between glycogen content in muscle and the percentage synthase in the activated (I) form. Exercise and insulin by themselves activate glycogen synthase by conversion to glycogen synthase I. Although small changes in the activity ratio (% I form) can lead to large changes in the rate of glycogen synthesis, glycogen synthase I appears to increase very little (approximately 25%) in response to glycogen depletion and returns to pre-exercise levels as glycogen levels return to normal. Thus glycogen resynthesis, which may increase 3- to 5-fold, may also be influenced by glucose-6-phosphate, which can activate glycogen synthase in the D form.(ABSTRACT TRUNCATED AT 400 WORDS)

Effect of reduced training on muscular strength and endurance in competitive swimmers.

Following 5 months of competitive training (approximately 9,000 yards.d-1, 6 d.wk-1), three groups of eight male swimmers performed 4 wk of either reduced training (3,000 yard.session-1) or inactivity. Two groups reduced their training to either 3 sessions.wk-1 (RT3) or 1 session.wk-1 (RT1), whereas the third group (IA) did no training. Measurement of muscular strength (biokinetic swim bench) showed no decrement in any group over the 4 wk. In contrast, swim power (tethered swim) was significantly decreased (P less than 0.05) in all groups, reaching a mean change of -13.6% by week 4. Blood lactate measured after a standard 200-yard (183 m) front crawl swim increased by 1.8, 3.5, and 5.5 mM over the 4 wk in groups RT3, RT1 and IA, respectively. In group RT1, stroke rate measured during the 200-yard swim significantly increased (P less than 0.05) from 0.54 +/- 0.03 to 0.59 +/- 0.03 strokes.-1 while stroke distance significantly decreased (P less than 0.05) from 2.50 +/- 0.08 to 2.29 +/- 0.13 m.stroke-1 during the 4-wk period. Both stroke rate and stroke distance were maintained in group RT3 over the 4 wk of reduced training. Group IA was not tested for stroke mechanics. Whereas maximal oxygen uptake decreases significantly (P less than 0.05) over the 4 wk in group RT1 (4.75 to 4.62 l.min-1), no change in maximal oxygen uptake was observed in group RT3. These results suggest that aerobic capacity is maintained over 4 wk of moderately reduced training (3 sessions.wk-1) in well-trained swimmers. Muscular strength was not diminished over 4 wk of reduced training or inactivity, but the ability to generate power during swimming was significantly reduced in all groups.

Gastric emptying during 1 h of cycling and running at 75% VO2max.

The purpose of this study was to compare gastric emptying (GE) responses during intense, prolonged cycling and running. It is important to discern whether gastric emptying (GE) responses are exercise-mode specific, since the findings of cycling and running studies are often compared and applied to one another. Ten male biathletes cycled (CY) and ran (R) for 1 h at 75% of their mode-specific VO2max or rested (S) and consumed water (SW, CYW, RW) or a 7% carbohydrate solution (SC, CYC, RC) at a rate of 10 ml.kg-1.h-1 (approximately 180 ml at 0, 15, 30, and 45 min). No differences were found between CYW, CYC, RW, RC, and SC for volume of drink emptied (mean +/- SE) (522.8 +/- 47.9 ml) and GE rate (range, 8.2 +/- 0.9 (RC) to 9.3 +/- 0.6 ml.min-1 (SC]. A mean of 72.7 +/- 5.7% of the total consumed volume was emptied. The GE rate during SW was significantly (P less than 0.05) greater than the other conditions (11.3 +/- 0.4 ml.min-1, 94.0 +/- 1.9% of total consumed volume emptied). Substantial volumes of water and a 7% carbohydrate solution are thus emptied from the stomach during prolonged, intense running and cycling, with no differences in GE between these exercise modes. These data suggest that recommendations concerning GE are reciprocal between running and cycling bouts similar to those in the current study.

Influence of selected carbohydrate drinks on cycling performance and glycogen use.

Eight well-trained male cyclists were used to determine the influence of carbohydrate feedings on exercise performance and muscle glycogen use. Two days prior to each trial, the subjects performed a 60-min "depletion ride" at 70% VO2max, which was followed by the ingestion of a high carbohydrate diet (approximately 500 g X -1). During the experimental trials, the men performed 2 h of cycling exercise and consumed 150 ml of 1 of 4 solutions at 24-min intervals. The drinks were: H2O (artificially flavored and sweetened); maltodextrin (5 g X 100 ml-1) and fructose (5 g X 100 ml-1); maltodextrin (7.7 g X 100 ml-1) and high fructose corn syrup (2.3 g X 100 ml-1); maltodextrin (3 g X 100 ml-1 and glucose (2 g X 100 ml-1). The amount of work completed during the four trials was not significantly different. Initial glycogen levels were high, and glycogen values were not significantly different at the beginning of exercise or at 90 min (185.35 +/- 3.26 and 91.93 +/- 3.39, respectively). Blood glucose was greater at 60 min in trial maltodextrin and glucose (5.70 +/- 0.36 mmoles X l-1), maltodextrin and high fructose corn syrup (6.05 +/- 0.54), and maltodextrin and fructose (6.03 +/- 0.42) compared to H2O (4.97 +/- 0.35) (P less than 0.05). Blood glucose remained elevated at 90 min during the maltodextrin and fructose and maltodextrin and high fructose corn syrup trials and at 120 min in the maltodextrin and fructose trial. No differences were observed between trials in blood lactate, serum glycerol, respiratory exchange ratio, or the subjects' perception of effort.(ABSTRACT TRUNCATED AT 250 WORDS)

Physiological responses to successive days of intense training in competitive swimmers.

To examine the physiological responses to successive days of intense training, 12 male collegiate swimmers doubled their training distance (4,266 +/- 264 to 8,970 +/- 161 m.d-1) while maintaining the intensity at approximately 95% VO2max for 10 d. Blood samples were obtained pre-exercise and immediately and 5 min after a sub-maximal (approximately 95% VO2max) front crawl swim (365.8 m) on days 0, 5, and 11. Swim performance was assessed from a maximal front crawl swim (365.8 m), two maximal front crawl sprints (22.9 m), and a semi-tethered swim power test. No significant changes were observed in performance. Pre-exercise serum cortisol (17.5 +/- 1.5, 19.5 +/- 1.6, and 20.6 +/- 1.2 micrograms.dl-1 for days 0, 5, and 11, respectively) and creatine kinase (56.2 +/- 7.7, 93.1 +/- 10.1, and 119.0 +/- 23.1 U.l-1 for days 0, 5, and 11, respectively) values were significantly elevated (P less than 0.05) on days 5 and 11 compared to day 0. Resting plasma catecholamine concentrations were higher but not significantly different (P greater than 0.05) at the end of the training period. Measurements of hemoglobin and hematocrit indicated a relative increase of 11.4 +/- 2.7% (P less than 0.05) in estimated plasma volume during the training period. Resting blood glucose values were unaffected by the training regimen while small but significant decreases in resting blood lactate values (1.01 +/- 0.06, 0.85 +/- 0.06, and 0.86 +/- 0.06 mmol.l-1 for days 0, 5, and 11, respectively) were observed on days 5 and 11. Resting heart rate and systolic blood pressure were not affected by the increased training load.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of exercise and carbohydrate composition on gastric emptying.

To examine the gastric emptying characteristics of selected test drinks varying in carbohydrate composition and concentration, twenty-five runners ingested 400 ml of a solution in one or more of a series of trials followed by either 15 min seated rest or 15 min running (50 to 70% VO2 max). The solutions tested at rest included water, 5.0% maltodextrin, 3.0% maltodextrin + 2% glucose (MG5.0), and 4.5% maltodextrin + 2.6% fructose (MF7.1). Solutions tested during running included water, MG5.0, MF7.1, 5.5% maltodextrin + 2% glucose, and 5.5% maltodextrin + 2% fructose. At rest and during running, water emptied significantly (P less than 0.5) faster than all other drinks. In the running trials, the volume of gastric residue of 5.5% maltodextrin + 2% fructose (221.7 +/- 11.0 ml) was significantly greater than water (103.4 +/- 19.0 ml), MG5.0 (153.3 +/- 16.8 ml), and MF7.1 (167.3 +/- 14.8), suggesting an inhibitory role of glucose on gastric emptying. Running resulted in a significantly lower volume of gastric residue of water, MG5.0, and MF7.1 (103.4 +/- 19.0, 153.3 +/- 16.8, and 167.3 +/- 14.8 ml, respectively) as compared to the corresponding drinks at rest (209.3 +/- 12.6, 287.7 +/- 16.0, and 271.0 +/- 17.8 ml, respectively). These results suggest a possible advantage for including maltodextrin and fructose as carbohydrate sources in athletic drinks. Furthermore, the rate of gastric emptying is enhanced while running, possibly due to increased mechanical movement of fluid within the stomach.

Fluid replacement during sustained activity in the heat: nutrient solution vs. water.

This study examined the thermoregulatory and hydrational status of men during sustained activity in a hot-dry (37 degrees C, 20% rh) environment while they consumed only a nutrient solution (nutrient), or consumed only colored, flavored water (control). Eleven heat acclimated young men attempted 24-h sustained activity experiments. These experiments consisted of alternating 45-min bouts of treadmill walking (410 W, approximately 30% VO2max) and rest (including sedentary activity). Data were analyzed through 13 h (after 13 h subjects began to discontinue testing). No significant differences between trials were observed for metabolic rate, fluid intake, skin or rectal temperature, sweating rate, plasma volume (as indicated by hemoglobin concentration) or plasma glucose concentrations. By the 8th h plasma osmolality was higher and by the 11th h plasma free fatty acids were lower during the nutrient trial compared to the control. In separate experiments with nine different men, the gastric emptying rates of the nutrient solution and water were compared during exercise (55% VO2max) in the heat (35 degrees C, 20% rh). The gastric emptying rates of the nutrient solution and water were similar (approximately 20 ml.min-1). These data indicate that during 13 h of sustained activity in a hot environment, the nutrient solution and water provided similar thermoregulatory and hydrational benefits.

High-fat load: mechanism(s) of insulin resistance in skeletal muscle.

Skeletal muscle from sedentary obese patients is characterized by depressed electron transport activity, reduced expression of genes required for oxidative metabolism, altered mitochondrial morphology and lower overall mitochondrial content. These findings imply that obesity, or more likely the metabolic imbalance that causes obesity, leads to a progressive decline in mitochondrial function, eventually culminating in mitochondrial dissolution or mitoptosis. A decrease in the sensitivity of skeletal muscle to insulin represents one of the earliest maladies associated with high dietary fat intake and weight gain. Considerable evidence has accumulated to suggest that the cytosolic ectopic accumulation of fatty acid metabolites, including diacylglycerol and ceramides, underlies the development of insulin resistance in skeletal muscle. However, an alternative mechanism has recently been evolving, which places the etiology of insulin resistance in the context of cellular/mitochondrial bioenergetics and redox systems biology. Overnutrition, particularly from high-fat diets, generates fuel overload within the mitochondria, resulting in the accumulation of partially oxidized acylcarnitines, increased mitochondrial hydrogen peroxide (H2O2) emission and a shift to a more oxidized intracellular redox environment. Blocking H2O2 emission prevents the shift in redox environment and preserves insulin sensitivity, providing evidence that the mitochondrial respiratory system is able to sense and respond to cellular metabolic imbalance. Mitochondrial H2O2 emission is a major regulator of protein redox state, as well as the overall cellular redox environment, raising the intriguing possibility that elevated H2O2 emission from nutrient overload may represent the underlying basis for the development of insulin resistance due to disruption of normal redox control mechanisms regulating protein function, including the insulin signaling and glucose transport processes.