Muscle Oxidative Potential Research Articles

Improving biologic predictors of cycling endurance performance with near-infrared spectroscopy derived measures of skeletal muscle respiration: E pluribus unum.

The study aim was to compare the predictive validity of the often referenced traditional model of human endurance performance (i.e. oxygen consumption, VO2, or power at maximal effort, fatigue threshold values, and indices of exercise efficiency) versus measures of skeletal muscle oxidative potential in relation to endurance cycling performance. We hypothesized that skeletal muscle oxidative potential would more completely explain endurance performance than the traditional model, which has never been collectively verified with cycling. Accordingly, we obtained nine measures of VO2 or power at maximal efforts, 20 measures reflective of various fatigue threshold values, 14 indices of cycling efficiency, and near‐infrared spectroscopy‐derived measures reflecting in vivo skeletal muscle oxidative potential. Forward regression modeling identified variable combinations that best explained 25‐km time trial time‐to‐completion (TTC) across a group of trained male participants (n = 24). The time constant for skeletal muscle oxygen consumption recovery, a validated measure of maximal skeletal muscle respiration, explained 92.7% of TTC variance by itself (Adj R 2 = .927, F = 294.2, SEE = 71.2, p < .001). Alternatively, the best complete traditional model of performance, including VO2max (L·min−1), %VO2max determined by the ventilatory equivalents method, and cycling economy at 50 W, only explained 76.2% of TTC variance (Adj R 2 = .762, F = 25.6, SEE = 128.7, p < .001). These results confirm our hypothesis by demonstrating that maximal rates of skeletal muscle respiration more completely explain cycling endurance performance than even the best combination of traditional variables long postulated to predict human endurance performance.

Ostreolysin induces browning of adipocytes and ameliorates hepatic steatosis.

Non-alcoholic fatty liver disease (NAFLD) is associated with all features of the metabolic syndrome. Deposition of excess triglycerides in liver cells, a hallmark of NAFLD, is associated with loss of insulin sensitivity. Ostreolysin (Oly) is a 15-kDa fungal protein known to interact with cholesterol-enriched raft-like membrane domains. We aim to test whether a recombinant version of Oly (rOly) can induce functional changes in vitro in adipocytes or in vivo in mice fed a high-fat diet (HFD). White preadipocyte 3T3-L1 cells or mouse primary adipocytes treated with rOly. Male C57BL/6 mice were fed a control or HFD and treated with saline or with rOly (1mg/kg BW) every other day for 4weeks. White preadipocyte 3T3-L1 cells or mouse primary adipocytes treated with rOly acquire a browning phenotype through activation of 5' adenosine monophosphate-activated protein kinase and downregulation of tumor necrosis factor α-mediated activation of IκB kinase ε and TANK-binding kinase 1. HFD-fed mice treated with rOly showed a 10% reduction in BW and improved glucose tolerance, which paralleled improved expression of liver and adipose functionality, metabolism, and inflammation status, mimicking the in vitro findings. This study provides first evidence of rOly's prevention of HFD-induced NAFLD by stimulating liver and adipose muscle tissue functionality and oxidative potential, improving glucose tolerance, and ameliorating the metabolic profile of diet-induced obese mice.

Sex Comparison of Knee Extensor Size, Strength, and Fatigue Adaptation to Sprint Interval Training.

Bagley, L, Al-Shanti, N, Bradburn, S, Baig, O, Slevin, M, and McPhee, JS. Sex comparison of knee extensor size, strength, and fatigue adaptation to sprint interval training. J Strength Cond Res 35(1): 64-71, 2021-Regular sprint interval training (SIT) improves whole-body aerobic capacity and muscle oxidative potential, but very little is known about knee extensor anabolic or fatigue resistance adaptations, or whether effects are similar for men and women. The purpose of this study was to compare sex-related differences in knee extensor size, torque-velocity relationship, and fatigability adaptations to 12-week SIT. Sixteen men and 15 women (mean [SEM] age: 41 [±2.5] years) completed measurements of total body composition assessed by dual energy X-ray absorptiometry, quadriceps muscle cross-sectional area (CSAQ) assessed by magnetic resonance imaging, the knee extensor torque-velocity relationship (covering 0-240°·s-1) and fatigue resistance, which was measured as the decline in torque from the first to the last of 60 repeated concentric knee extensions performed at 180°·s-1. Sprint interval training consisted of 4 × 20-second sprints on a cycle ergometer set at an initial power output of 175% of power at V̇o2max, 3 times per week for 12 weeks. Quadriceps muscle cross-sectional area increased by 5% (p = 0.023) and fatigue resistance improved 4.8% (p = 0.048), with no sex differences in these adaptations (sex comparisons: p = 0.140 and p = 0.282, respectively). Knee extensor isometric and concentric torque was unaffected by SIT in both men and women (p > 0.05 for all velocities). Twelve-week SIT, totaling 4 minutes of very intense cycling per week, significantly increased fatigue resistance and CSAQ similarly in men and women, but did not significantly increase torque in men or women. These results suggest that SIT is a time-effective training modality for men and women to increase leg muscle size and fatigue resistance.

Irisin is more strongly predicted by muscle oxidative potential than adiposity in non-diabetic men.

Numerous controversies surround the peptide hormone irisin. Although implicated as a myokine promoting the browning of adipose tissue in rodents, its roles in humans remain unclear. Contradictory results have also been found with respect to the relationships between adiposity or metabolic health and plasma irisin levels in humans. We investigated the relationship between irisin levels and body composition (hydrostatic weighing), insulin sensitivity (hyperinsulinemic-euglycemic clamp), fitness level (ergocycle VO2max) and skeletal muscle metabolic profile in 53 men (aged 34-53 years) from four groups: sedentary non-obese controls (body mass index [BMI] <25 kg/m(2)), sedentary obese (BMI >30 kg/m(2)), sedentary obese glucose-intolerant, and non-obese highly trained endurance active. Baseline plasma irisin levels were significantly different between groups, being lowest in trained men (140.6 ± 38.2 ng/mL) and highest in metabolically deteriorated glucose-intolerant subjects (204.0 ± 50.5 ng/mL; ANOVA p = 0.01). Including all subjects, irisin levels were positively associated with adiposity (e.g. fat mass, r = 0.430, p < 0.01) and negatively associated with fitness (r = -0.369, p < 0.01), insulin sensitivity (M/I, r = -0.355, p < 0.01) and muscle citrate synthase (CS) activity (r = -0.482, p < 0.01). Most correlations lost statistical significance when excluding active individuals, except for insulin resistance (r = -0.413, p < 0.01) and CS (r = -0.462, p < 0.01). Multiple regression analyses reveal CS as the strongest independent predictor of irisin levels (r(2) range 0.214 to 0.237). We conclude that muscle oxidative potential is an important factor linked to circulating irisin levels.

Predictors of body composition and body energy changes in response to chronic overfeeding

ObjectiveWe have previously shown that 24 young lean men (12 pairs of identical twins) subjected to a standardized 353 MJ (84 000 kcal) overfeeding protocol over 100 days exhibited individual differences in body weight and composition gains. The mean (+SD) gains in fat mass (FM) and fat-free mass (FFM) were 5.4+1.9 kg and 2.7+1.5 kg for a total body energy (BE) gain of 221+75 MJ representing 63% of the energy surplus consumed. We report here on the most important baseline correlates of these overfeeding-induced changes with the aim of identifying biomarkers of the response.ResultsBaseline maximal oxygen uptake per kilogram body mass was negatively correlated with gains in weight, FM, and BE (all p<0.05). Enzyme activities indicative of skeletal muscle oxidative potential correlated with gains in FM and BE (all p<0.05). Baseline TSH levels in response to a TRH stimulation correlated positively with changes in FM-to-FFM ratio (p<0.05). Plasma concentrations of androstenediol-sulfate, dehydroepiandrosterone, and 17-hydroxy pregnenolone were negatively correlated with gains in FM and BE (0.01<p<0.05), while level of estrone was negatively and androsterone-glucoronide was positively correlated with FFM gains (p<0.05). Baseline leptin and abdominal fat cell size correlated positively with gains in weight, FM, and BE (p<0.05). When compared to the six highest BE gainers, the six lowest gainers exhibited higher thermic effect of a meal (TEM) and plasma levels of total testosterone, cortisol, estradiol, androstenedione, and androstenediol-sulfate (all p<0.05). High baseline levels of total TEM, testosterone, and androstenediol-sulfate were associated with lower FM gains whereas high baseline levels of FT4 and estrone were found in low-FFM gainers.ConclusionAlthough none of the variables exerted individually an overwhelmingly strong influence on overfeeding-induced changes, baseline FFM, maximal oxygen uptake, muscle oxidative capacity, androgens, and leptin levels were the most consistent significant biomarkers of the responsiveness to chronic overfeeding.

Combined Effects of Whole-Body Vibration, Resistance Exercise, and Vascular Occlusion on Skeletal Muscle and Performance

The purpose of this study was to evaluate the effects of a new high-intensity training modality comprised of vibration exercise with superimposed resistance exercise and vascular occlusion (vibroX) on skeletal muscle and performance. Young untrained women were randomized to either train in a progressive mode on 3 days per week for 5 weeks ( N=12) or to maintain a sedentary lifestyle ( N=9). VibroX increased peak cycling power (+9%, P=0.001), endurance capacity (+57%, P=0.002), ventilatory threshold (+12%, P<0.001), and end-test torque (+15%, P=0.002) relative to the sedentary group. Training load increased by 84.5% ( P<0.001) after vibroX. The increases were paralleled by increases in myosin heavy chain type 1 vastus lateralis muscle fiber cross-sectional area (+14%, P=0.031) and proportion (+17%, P=0.015), thigh lean mass (+4%, P=0.001), capillary-to-fiber ratio (+14%, P=0.003), and cytochrome c oxidase activity. Conversely, maximal values for oxygen consumption, cardiac output, isokinetic leg extension power and jumping power remained unaffected. Notably, vastus lateralis muscle adaptations were achieved with a very low weekly training volume. We conclude that vibroX quickly increases muscle (fiber) size, capillarization, and oxidative potential, and markedly augments endurance capacity in young women.

Effects of Two Different Half-Squat Training Programs on Fatigue During Repeated Cycling Sprints in Soccer Players

This study compared the effects of two different half-squat training programs on the repeated-sprint ability of soccer players during the preseason. Twenty male professional soccer players were divided into 2 groups: One group (S-group) performed 4 sets of 5 repetitions with 90% of their 1-repetition maximum (1RM), and the other group (H-group) performed 4 sets of 12 repetitions with 70% of 1RM, 3 times per week for 6 weeks, in addition to their common preseason training program. Repeated-sprint ability was assessed before and after training by 10 × 6-second cycle ergometer sprints separated by 24 seconds of passive recovery. Maximal half-squat strength increased significantly in both groups (p < 0.01), but this increase was significantly greater in the S-group compared with the H-group (17.3 ± 1.9 vs. 11.0 ± 1.9%, p < 0.05). Lean leg volume (LLV) increased only in the H-group. Total work over the 10 sprints improved in both groups after training, but this increase was significantly greater in the second half (8.9 ± 2.6%) compared with the first half of the sprint test (3.2 ± 1.7%) only in the S-group. Mean power output (MPO) expressed per liter of LLV was better maintained during the last 6 sprints posttraining only in the S-group, whereas there was no change in MPO per LLV in the H-group over the 10 sprints. These results suggest that resistance training with high loads is superior to a moderate-load program, because it increases strength without a change in muscle mass and also results in a greater improvement in repeated sprint ability. Therefore, resistance training with high loads may be preferable when the aim is to improve maximal strength and fatigue during sprinting in professional soccer players.

Time-dependent effects of short-term training on muscle metabolism during the early phase of exercise

In this study, we investigated the hypothesis that the metabolic adaptations observed during steady-state exercise soon after the onset of training would be displayed during the nonsteady period of moderate exercise and would occur in the absence of increases in peak aerobic power (Vo2peak) and in muscle oxidative potential. Nine untrained males [age = 20.8 +/- 0.70 (SE) yr] performed a cycle task at 62% Vo2peak before (Pre-T) and after (Post-T) training for 2 h/day for 5 days at task intensity. Tissue samples extracted from the vastus lateralis at 0 min (before exercise) and at 10, 60, and 180 s of exercise, indicated that at Pre-T, reductions (P < 0.05) in phosphocreatine and increases (P < 0.05) in creatine, inorganic phosphate, calculated free ADP, and free AMP occurred at 60 and 180 s but not at 10 s. At Post-T, the concentrations of all metabolites were blunted (P < 0.05) at 60 s. Training also reduced (P < 0.05) the increase in lactate and the lactate-to-pyruvate ratio observed during exercise at Pre-T. These adaptations occurred in the absence of change in Vo2peak (47.8 +/- 1.7 vs. 49.2 +/- 1.7 mlxkg(-1)xmin(-1)) and in the activities (molxkg protein(-1)xh(-1)) of succinic dehydrogenase (3.48 +/- 0.21 vs. 3.77 +/- 0.35) and citrate synthase (7.48 +/- 0.61 vs. 8.52 +/- 0.65) but not cytochrome oxidase (70.8 +/- 5.1 vs. 79.6 +/- 6.6 U/g protein; P < 0.05). It is concluded that the tighter metabolic control observed following short-term training is initially expressed during the nonsteady state, probably as a result of increases in oxidative phosphorylation that is not dependent on changes in Vo2peak while the role of oxidative potential remains uncertain.

Gene‐Nutrition and Gene‐Physical Activity Interactions in the Etiology of Obesity

Gene‐Nutrition and Gene‐Physical Activity Interactions in the Etiology of Obesity

Training-induced Adaptation in Glucose Tolerance In Inbred Rats

PURPOSE: The purpose of the study was to determine if 1) training-induced adaptive change in glucose tolerance would depend on genetic factors and 2) training-induced change in muscle oxidative potential would be associated with change in glucose tolerance. METHODS: Two inbred strains of rats (DA=15 rats and COP=13 rats) with different genetic background were divided into control and training groups. Rats in the training group underwent swim training regimen, which consisted of two 3-hour long bouts separated by a 45-min long rest period, 6 days/wk for 4 weeks. At the completion of the training, rats in both groups underwent a glucose tolerance test. Blood glucose level was determined using a glucometer before and at 5, 10, 20, 50 and 75 minutes after i.p. glucose injection (2g/kg BW). The activity of citrate synthase (CS) in red and white gastrocnemius, soleus, and eipitrochlearis was determined at 25°C. The level of glucose tolerance was determined by calculating the area under curve (AUC) using a trapezoid rule. RESULTS: The training-induced improvement in glucose tolerance was 58% (P < 0.001) in DA and 25% (P < 0.01) in COP without difference between the two strains in the control groups. Glucose tolerance in the trained DA was significantly better than that in the trained COP, showing the AUC in the trained DA was significantly lower (47%, P < 0.001) than that in the trained COP. CS activity in red muscles (red gastrocnemius and soleus) was increased significantly in both DA (36-59%, P < 0.01) and COP (42%, P < 0.01). There was no change in CS in epitrochlearis in both strains but a significant increase in white gastrocnemius in COP (47%, P < 0.05) not in DA. CONCLUSIONS: The results demonstrate that training-induced improvement in glucose tolerance depends on genetic factors and a change in oxidative potential in skeletal muscle is not parallel with training-induced change in glucose tolerance.

Increased muscle oxidative potential following resistance training induced fibre hypertrophy in young men

Some evidence suggests that resistance training may lower relative muscle mitochondrial content via "dilution" of the organelle in a larger muscle fibre. Such an adaptation would reduce fatigue resistance, as well as compromise oxidative ATP synthesis and the capacity for fatty-acid oxidation. We investigated the effect of resistance training on mitochondrial enzymes of the citric acid cycle (citrate synthase; CS) and beta-oxidation (beta-hydroxyacyl CoA dehydrogenase; beta-HAD), as well as markers of the potential for glucose phosphorylation (hexokinase; HK) and glycolysis (phosphofructokinase; PFK). Twelve untrained men (21.9 +/- 0.5 y; 1.79 +/- 0.03 m; 83.2 +/- 3.2 kg) participated in a 12 week progressive resistance-training program. Muscle biopsies were taken from the vastus lateralis before (PRE) and after (POST) training. Training increased mean muscle fibre cross-sectional area (p < 0.05) and the activities of CS (PRE = 4.53 +/- 0.44 mol.kg protein(-1).h(-1); POST = 5.63 +/- 0.40 mol.kg protein(-1).h(-1); p < 0.001) and beta-HAD (PRE = 2.55 +/- 0.28 mol.kg protein(-1).h(-1); POST = 3.11 +/- 0.21 mol.kg protein(-1).h(-1); p < 0.05). The activity of HK increased 42% (p < 0.05), whereas the activity of PFK remained unchanged. We conclude that resistance training provides a stimulus for improving muscle oxidative potential, as reflected by the increased activities of CS and beta-HAD following resistance training induced hypertrophy.

Effect of short-term sprint interval training on human skeletal muscle carbohydrate metabolism during exercise and time-trial performance

Our laboratory recently showed that six sessions of sprint interval training (SIT) over 2 wk increased muscle oxidative potential and cycle endurance capacity (Burgomaster KA, Hughes SC, Heigenhauser GJF, Bradwell SN, and Gibala MJ. J Appl Physiol 98: 1895-1900, 2005). The present study tested the hypothesis that short-term SIT would reduce skeletal muscle glycogenolysis and lactate accumulation during exercise and increase the capacity for pyruvate oxidation via pyruvate dehydrogenase (PDH). Eight men [peak oxygen uptake (VO2 peak)=3.8+/-0.2 l/min] performed six sessions of SIT (4-7x30-s "all-out" cycling with 4 min of recovery) over 2 wk. Before and after SIT, biopsies (vastus lateralis) were obtained at rest and after each stage of a two-stage cycling test that consisted of 10 min at approximately 60% followed by 10 min at approximately 90% of VO2 peak. Subjects also performed a 250-kJ time trial (TT) before and after SIT to assess changes in cycling performance. SIT increased muscle glycogen content by approximately 50% (main effect, P=0.04) and the maximal activity of citrate synthase (posttraining: 7.8+/-0.4 vs. pretraining: 7.0+/-0.4 mol.kg protein -1.h-1; P=0.04), but the maximal activity of 3-hydroxyacyl-CoA dehydrogenase was unchanged (posttraining: 5.1+/-0.7 vs. pretraining: 4.9+/-0.6 mol.kg protein -1.h-1; P=0.76). The active form of PDH was higher after training (main effect, P=0.04), and net muscle glycogenolysis (posttraining: 100+/-16 vs. pretraining: 139+/-11 mmol/kg dry wt; P=0.03) and lactate accumulation (posttraining: 55+/-2 vs. pretraining: 63+/-1 mmol/kg dry wt; P=0.03) during exercise were reduced. TT performance improved by 9.6% after training (posttraining: 15.5+/-0.5 vs. pretraining: 17.2+/-1.0 min; P=0.006), and a control group (n=8, VO2 peak=3.9+/-0.2 l/min) showed no change in performance when tested 2 wk apart without SIT (posttraining: 18.8+/-1.2 vs. pretraining: 18.9+/-1.2 min; P=0.74). We conclude that short-term SIT improved cycling TT performance and resulted in a closer matching of glycogenolytic flux and pyruvate oxidation during submaximal exercise.

A comment on Burgomaster et al. and a general plea to consider behavioral influences in human physiology studies

Burgomaster, Kirsten A., Scott C. Hughes, George J. F. Heigenhauser, Suzanne N. Bradwell, and Martin J. Gibala. Six sessions of sprint interval training increases muscle oxidative potential and cyc...

Six sessions of sprint interval training increases muscle oxidative potential and cycle endurance capacity in humans

Parra et al. (Acta Physiol. Scand 169: 157-165, 2000) showed that 2 wk of daily sprint interval training (SIT) increased citrate synthase (CS) maximal activity but did not change "anaerobic" work capacity, possibly because of chronic fatigue induced by daily training. The effect of fewer SIT sessions on muscle oxidative potential is unknown, and aside from changes in peak oxygen uptake (Vo(2 peak)), no study has examined the effect of SIT on "aerobic" exercise capacity. We tested the hypothesis that six sessions of SIT, performed over 2 wk with 1-2 days rest between sessions to promote recovery, would increase CS maximal activity and endurance capacity during cycling at approximately 80% Vo(2 peak). Eight recreationally active subjects [age = 22 +/- 1 yr; Vo(2 peak) = 45 +/- 3 ml.kg(-1).min(-1) (mean +/- SE)] were studied before and 3 days after SIT. Each training session consisted of four to seven "all-out" 30-s Wingate tests with 4 min of recovery. After SIT, CS maximal activity increased by 38% (5.5 +/- 1.0 vs. 4.0 +/- 0.7 mmol.kg protein(-1).h(-1)) and resting muscle glycogen content increased by 26% (614 +/- 39 vs. 489 +/- 57 mmol/kg dry wt) (both P < 0.05). Most strikingly, cycle endurance capacity increased by 100% after SIT (51 +/- 11 vs. 26 +/- 5 min; P < 0.05), despite no change in Vo(2 peak). The coefficient of variation for the cycle test was 12.0%, and a control group (n = 8) showed no change in performance when tested approximately 2 wk apart without SIT. We conclude that short sprint interval training (approximately 15 min of intense exercise over 2 wk) increased muscle oxidative potential and doubled endurance capacity during intense aerobic cycling in recreationally active individuals.

DIETARY OBESITY-RESISTANCE AND MUSCLE OXIDATIVE ENZYME ACTIVITIES OF FAST-TWITCH FIBER DOMINANT RATS

The effects of a low- or high-fat diet on hereditary fast-twitch fiber dominant rats (FFDR) and control rats (CR) were investigated to clarify the relation between muscle fiber composition and fat accumulation. The CR and FFDR were divided into low-fat (20% of calories from fat) or high-fat (60% of calories from fat) diet groups; CR with a low-fat diet (CL), CR with a high-fat diet (CH), FFDR with a low-fat diet (FL), and FFDR with a high-fat diet (FH). After 6 wks of following such diets, the total weight gain in CH was found to be higher than FL and FH. The percentage of abdominal fat in CH was the highest while the food intake did not differ among the 4 groups. The percentage of type I fibers of M. gastrocnemius and soleus in FFDR were lower than in the CR, and the type IIDX fibers of M. gastrocnemius and type the IIA fibers of M. soleus in FFDR were higher than in the CR. No significant difference in the fiber composition was observed in M. plantaris. The succinate dehydrogenase (SDH) activity in type IIA fiber was the highest of all fiber types. The change in the SDH activity by a high-fat diet in type I and IIA fibers of M. soleus and type I fibers of M. plantaris in FH were higher than in CH. Citrate synthase (CS) and β-hydroxyacyl CoA dehydrogenase (HAD) activity of M. plantaris in FFDR were higher than in CR. These results therefore clearly indicated that the FFDR were more obesity-resistant than the CR. These results suggest that the muscle oxidative potential and its adaptability, rather than the fiber composition appear to be possible determinants of obesity. Supported by research grants from The Japanese Ministry of Education, Science and Culture (No. 11558002).

Changes in skeletal muscle in males and females following endurance training

Gender differences in substrate selection have been reported during endurance exercise. To date, no studies have looked at muscle enzyme adaptations following endurance exercise training in both genders. We investigated the effect of a 7-week endurance exercise training program on the activity of beta-oxidation, tricarboxylic acid cycle and electron transport chain enzymes, and fiber type distribution in males and females. Training resulted in an increase in VO2peak, for both males and females of 17% and 22%, respectively (P < 0.001). The following muscle enzyme activities increased similarly in both genders: 3-beta-hydroxyacyl CoA dehydrogenase (38%), citrate synthase (41%), succinate-cytochrome c oxidoreductase (41%), and cytochrome c oxidase (COX; 26%). The increase in COX activity was correlated (R2 = 0.52, P < 0.05) with the increase in VO2peak/fat free mass. Fiber area, size, and % area were not affected by training for either gender, however, males had larger Type II fibers (P < 0.05) and females had a greater Type I fiber % area (P < 0.05). Endurance training resulted in similar increases in skeletal muscle oxidative potential for both males and females. Training did not affect fiber type distribution or size in either gender.

Effect of short-term exercise training on angiogenic growth factor gene responses in rats.

We investigated whether 1) 5 days of exercise training would reduce the acute exercise-induced increase in skeletal muscle growth factor gene expression; and 2) reductions in the increase in growth factor gene expression in response to short-term exercise training would be coincident with increases in skeletal muscle oxidative potential. Female Wistar rats were used. Six groups (rest; exercise for 1-5 consecutive days) were used to measure the growth factor response through the early phases of an exercise training program. Vascular endothelial growth factor (VEGF), transforming growth factor-beta1 (TGF-beta1), and basic fibroblast growth factor (bFGF) mRNA were analyzed from the left gastrocnemius by quantitative Northern blot. Citrate synthase activity was analyzed from the right gastrocnemius. VEGF and TGF-beta1 mRNA increased after each of 5 days of exercise training, whereas exercise on any day did not increase bFGF mRNA. On day 1, the VEGF mRNA response was significantly greater than on days 2-5. However, the reduced increase in VEGF mRNA observed on days 2-5 was not coincident with increases in citrate synthase activity. These findings suggest that, in skeletal muscle, 1) VEGF and TGF-beta1 mRNA are increased through 5 days of exercise training and 2) the reduced exercise-induced increase in VEGF mRNA responses on days 2-5 does not result from increases in oxidative potential.

Chronic beta-blockade increases skeletal muscle beta-adrenergic-receptor density and enhances contractile force.

The effects of a chronic 14-day administration of a selective beta2-adrenergic-receptor antagonist (ICI-118551) on skeletal muscle were evaluated in female Sprague-Dawley rats. Chronic ICI-118551 treatment did not modify muscle mass, oxidative potential, or protein concentration of the medial gastrocnemius muscle, suggesting that maintenance of these skeletal muscle characteristics is not dependent on beta2-adrenergic-receptor stimulation. However, the drug treatment increased beta-adrenergic-receptor density of the lateral gastrocnemius (42%) and caused an increase in specific (g/g) isometric in situ contractile forces of the medial gastrocnemius [twitch, 56%; tetanic (200 Hz), 28%]. The elevated contractile forces observed after a chronic treatment with ICI-118551 were completely abolished when the beta2-adrenergic antagonist was also administered acutely before measurement of contractile forces, suggesting that this response is beta2-adrenergic-receptor dependent. Possible mechanisms for the increased forces were studied. Caffeine administration potentiated twitch forces but had little effect on tetanic force in control animals. Administration of dibutyryl adenosine 3',5'-cyclic monophosphate in control animals also resulted in small increases of twitch force but did not modify tetanic forces. We conclude that increases in beta-adrenergic-receptor density and the stimulation of the receptors by endogenous catecholamines appear to be responsible for increased contractile forces but that the mechanism remains to be demonstrated.

Metabolic changes associated with sustained 48-Hr shivering thermogenesis in the newborn pig

Metabolic changes associated with sustained 48-hr shivering thermogenesis were studied in piglets maintained at 34 (thermoneutrality) or 25°C (cold) between 6 and 54 hr of life. Despite their high shivering activity and elevated heat production, cold-exposed piglets exhibited a slightly lower rectal temperature than thermoneutral animals (-1.1°C; P < 0.01) at the end of the treatment. The enhancement of heat production and shivering activity were associated with a decrease in muscle glycogen (− 47%; P < 0.05) and total lipid content (− 23%; P < 0.05), a reduction of blood lactate levels ( P < 0.05) and an enhancement of muscle cytochrome oxidase activity (+20%; P < 0.05), which suggests that muscle oxidative potential was increased by cold exposure. Potential for capturing lipids (lipoprotein lipase activity) was also higher in the red rhomboideus muscle (+ 71%; P < 0.01) and lower in adipose tissue (−58%; P < 0.01) of the cold-exposed piglets. Measurements performed at the mitochondrial level show no changes in rhomboideus muscle, but respiratory capacities (state IV and FCCP-stimulated respiration) and intermyofibrillar mitochondria oxidative and phosphorylative (creatine kinase activity) capacities were enhanced in longissimus dorsi muscle ( P < 0.05). These changes may contribute to provide muscles with nonlimiting amount of readily oxidable substrates and ATP necessary for shivering thermogenesis. A rise in plasma norepinephrine levels was also observed during the second day of cold exposure ( P < 0.05).

Progressive effect of endurance training on metabolic adaptations in working skeletal muscle.

We investigated the hypothesis that a program of prolonged endurance training, previously shown to decrease metabolic perturbations to acute exercise within 5 days of training, would result in greater metabolic adaptations after a longer training duration. Seven healthy male volunteers [O2 consumption = 3.52 +/- 0.20 (SE) l/min] engaged in a training program consisting of 2 h of cycle exercise at 59% of pretraining peak O2 consumption (VO2peak) 5-6 times/wk. Responses to a 90-min submaximal exercise challenge were assessed pretraining (PRE) and after 5 and 31 days of training. On the basis of biopsies obtained from the vastus lateralis muscle, it was found that, after 5 days of training, muscle lactate concentration, phosphocreatine (PCr) hydrolysis, and glycogen depletion were reduced vs. PRE (all P < 0.01). Further training (26 days) showed that, at 31 days, the reduction in PCr and the accumulation of muscle lactate was even less than at 5 days (P < 0.01). Muscle oxidative potential, estimated from the maximal activity of succinate dehydrogenase, was increased only after 31 days of training (+41%; P < 0.01). In addition, VO2peak was only increased (10%) by 31 days (P < 0.05). The results show that a period of short-term training results in many characteristic training adaptations but that these adaptations occurred before increases in mitochondrial potential. However, a further period of training resulted in further adaptations in muscle metabolism and muscle phosphorylation potential, which were linked to the increase in muscle mitochondrial capacity.