Low-intensity exercise can increase muscle mass and strength proportionally to enhanced metabolic stress under ischemic conditions

Skeletal muscle bulk and strength are becoming important therapeutic targets in medicine. To increase muscle mass, however, intensive, long-term mechanical stress must be applied to the muscles, and such stress is often accompanied by orthopedic and cardiovascular problems. We examined the effects of circulatory occlusion in resistance training combined with a very low-intensity mechanical load on enhancing muscular metabolic stress and thereby increasing muscle bulk. Muscular metabolic stress, as indicated by the increases in inorganic phosphate (P(i)) and a decrease in intramuscular pH, was evaluated by (31)P-magnetic resonance spectroscopy during unilateral plantar-flexion at 20% of the one-repetition maximum (1-RM) with circulatory occlusion for 2 min in 14 healthy, male untrained participants (22 yr) at baseline. Participants performed two sets of the same exercise with a 30-s rest between sets, 2 times/day, 3 days/wk, for 4 wk. The muscle cross-sectional area (MCA) of the plantar-flexors and the 1-RM were measured at baseline and after 2 and 4 wk of training. MCA and 1-RM were significantly increased after 2 and 4 wk (P < 0.05, respectively). The increase in MCA at 2 wk was significantly (P < 0.05) correlated with the changes in P(i) (r = 0.876) and intramuscular pH (r = 0.601). Furthermore, the increases in MCA at 4 wk and 1-RM at 2 wk were also correlated with the metabolic stress. Thus enhanced metabolic stress in exercising muscle is a key mechanism for favorable effects by resistance training. Low-intensity resistance exercise provides successful outcomes when performed with circulatory occlusion, even with a short training period.     

In vivo magnetic resonance spectroscopy in chronic fatigue syndrome

The pathogenic mechanisms of chronic fatigue syndrome (CFS) are not clearly known. Fatigue, poor short-term memory and muscle pain are the most disabling symptoms in CFS. Research data on magnetic resonance spectroscopy (MRS) of muscles and brain in CFS patients suggest a cellular metabolic abnormality in some cases. 31P MRS of skeletal muscles in a subset of patients indicate early intracellular acidosis in the exercising muscles. 1H MRS of the regional brain areas in CFS have shown increased peaks of choline derived from the cell membrane phospholipids. Cell membrane oxidative stress may offer a common explanation for the observed MRS changes in the muscles and brain of CFS patients and this may have important therapeutic implications. As a research tool, MRS may be used as an objective outcome measure in the intervention studies. In addition, regional brain 1H MRS has the potential for wider use to substantiate a clinical diagnosis of CFS from other disorders of unexplained chronic fatigue.     

The effect of iron limitation on glycerol production and expression of the isogenes for NAD(+)-dependent glycerol 3-phosphate dehydrogenase in Saccharomyces cerevisiae

The forearm flexor muscles of 56 untrained volunteers (26 women and 30 men) were examined by 31P magnetic resonance spectroscopy, during a rest-exercise-recovery protocol, in order to document the impact of gender on muscle energetics. Absolute concentrations of high-energy phosphate compounds, intracellular pH and rates of aerobic and anaerobic ATP production were calculated. An inverse correlation was found between body mass index (BMI) and power output in women but not in men. After correcting for power output and BMI, the measured energy cost of contraction was twice larger for women than for men. This increase was also reflected in larger ATP production from aerobic and anaerobic pathways. This higher energy cost might be explained in part by differences in local muscle mass, a higher impact of fatness, but also by a reduced metabolic efficiency of muscle fibers in untrained women.     

Skeletal muscle type comparison of pyruvate dehydrogenase phosphatase activity and isoform expression: effects of obesity and endurance training

Pyruvate dehydrogenase (PDH) plays an important role in regulating carbohydrate metabolism in skeletal muscle. PDH is activated by PDH phosphatase (PDP) and deactivated by PDH kinase (PDK). Obesity has a large negative impact on skeletal muscle carbohydrate metabolism, whereas endurance training has been shown to improve regulatory control of skeletal muscle carbohydrate metabolism, more so when coupled with obesity. A majority of this literature has focused on PDK, with little information available on PDP. To determine the relative role of PDP in regulating skeletal muscle PDH activity with obesity and endurance training, obese and lean Zucker rats remained sedentary or were endurance trained (1 h/day, 5 days/wk) for a period of 8 wk. Soleus, red gastrocnemius, (RG), and white gastrocnemius (WG) muscles were sampled after the training period. The main findings were 1) obesity resulted in a 46% decrease in PDP activity expressed per milligram extracted mitochondrial protein only in RG, while PDP isoform content was unchanged; 2) 8 wk of endurance training led to a significant 1.4-2.2-fold increase in PDP activity of all muscle examined from obese rats, and the concomitant increase in PDP1 protein was only seen in soleus and RG; 3) 8 wk of endurance training led to a trending 1.4-2.2-fold increase in PDP activity of all muscle examined from obese rats, and the concomitant increase in PDP1 protein was only seen in soleus and RG; and 4) PDP2 protein content was not affected by obesity or training. These results suggest that decreased PDP activity in oxidative skeletal muscles may play a role in the impairment of carbohydrate metabolism in obese rats, which is reversible with endurance training.     

Gender modulates the energy cost of muscle contraction in untrained healthy subjects. A P magnetic resonance spectroscopy analysis

The forearm flexor muscles of 56 untrained volunteers (26 women and 30 men) were examined by ³¹P magnetic resonance spectroscopy, during a rest-exercise-recovery protocol, in order to document the impact of gender on muscle energetics. Absolute concentrations of high-energy phosphate compounds, intracellular pH and rates of aerobic and anaerobic ATP production were calculated. An inverse correlation was found between body mass index (BMI) and power output in women but not in men. After correcting for power output and BMI, the measured energy cost of contraction was twice larger for women than for men. This increase was also reflected in larger ATP production from aerobic and anaerobic pathways. This higher energy cost might be explained in part by differences in local muscle mass, a higher impact of fatness, but also by a reduced metabolic efficiency of muscle fibers in untrained women.     

Physiological basis of muscle functional MRI

Muscle functional magnetic resonance imaging (MRI) refers to changes in the contrast properties of certain MR images that occur in exercising muscles. In part, these changes result indirectly from increased rates of cellular energy metabolism, which alter the image contrast properties by increasing the water content and by decreasing the intracellular pH. Also, increases in blood oxygen extraction cause a rapidly evolving, small, and negative contribution to signal. Together, these changes produce a complex time course of contrast changes during exercise. Analysis of this time course may provide insight into the physiology of exercising muscles. These contrast changes also provide a non-invasive method for determining the spatial pattern of muscle activation.     

Improved functional vasodilation in obese Zucker rats following exercise training

Obese individuals exhibit impaired functional vasodilation and exercise performance. We have demonstrated in obese Zucker rats (OZ), a model of morbid obesity, that insulin resistance impairs functional vasodilation via an increased thromboxane receptor (TP)-mediated vasoconstriction. Chronic treadmill exercise training improves functional vasodilation in the spinotrapezius muscle of the OZ, but the mechanisms responsible for the improvement in functional vasodilation are not clear. Based on evidence that exercise training improves insulin resistance, we hypothesized that, in the OZ, exercise training increases functional vasodilation and exercise capability due to decreases TP-mediated vasoconstriction associated with improved insulin sensitivity. Six-week-old lean Zucker rats (LZ) and OZ were exercised on a treadmill (24 m/min, 30 min/day, 5 days/wk) for 6 wk. An oral glucose tolerance test was performed at the end of the training period. We measured functional vasodilation in both exercise trained (spinotrapezius) and nonexercise trained (cremaster) muscles to determine whether the improved functional vasodilation following exercise training in OZ is due to a systemic improved insulin resistance. Compared with LZ, the sedentary OZ exhibited impairments in glucose tolerance and functional vasodilation in both muscles. The TP antagonist SQ-29548 improved the vasodilator responses in the sedentary OZ with no effect in the LZ. Exercising training of the LZ increased the functional vasodilation in spinotrapezius muscle, with no effect in the cremaster muscle. Exercising training of the OZ improved glucose tolerance, along with increased functional vasodilation, in both the spinotrapezius and cremaster muscles. SQ-29548 treatment had no effect on the vasodilator responses in either cremaster or spinotrapezius muscles of the exercise-trained OZ. These results suggest that, in the OZ, there is a global effect of exercising training to improve insulin resistance and increase functional vasodilation via a decreased TP-mediated vasoconstriction.     

The effect of unilateral isokinetic strength training on local adipose and muscle tissue morphology, thickness, and enzymes.

One-leg exercise of 5 weeks duration in 10 healthy middleaged women resulted in a significant increment of muscle force in the exercising leg and in a less, but at some angular velocities also significant, increase in the nonexercising leg. The thickness of subcutaneous tissue measured by ultrasound and skinfold caliper decreased, while muscle thickness increased in the exercising leg only. The increased thickness of muscle tissue was associated with an increase in the relative number and relative fiber area of type II fibers in the exercising leg. The mean fiber area of type IIB fibers increased significantly as well as the activity of lactate dehydrogenase and myokinase. The decrease of thickness of subcutaneous adipose tissue was not associated with a significant decrease in fat cell size and was probably due to geometrical factors secondary to hypertrophy of the underlying muscle. It is concluded that the relationship between lean and fat components of the human thigh is significantly influenced by changes in the activity of the thigh skeletal muscles, but a local dynamic strength training program can hardly be used for local emptying of the fat depot over the exercising muscles.     

Author index for volume 181, number 2

A phosphodiester, which comes into resonance at 0.4 ppm in the ³¹P nuclear magnetic resonance spectrum of intact muscles, has been isolated from the pectoralis muscle of chickens with hereditary muscular dystrophy by perchloric acid extraction, barium and alcoholic fractionation, and chromatographic isolation procedures. The compound,l-serine ethanolamine phosphodiester, whose presence is a characteristic of the diseased chicken muscle, has been characterized by ³¹P, ¹³C, and ¹H nuclear magnetic resonance as well as by chemical and chromatographic procedures.     

Phosphate metabolites in muscular contraction caused by magnetic stimulation

The metabolism of high energy phosphates during muscular contraction due to direct electrical stimulation, indirect stimulation via nerve excitation, and magnetic stimulation was studied in isolated muscles (frog sartorius muscles) by (31)P nuclear magnetic resonance ((31)P-NMR). Twitch amplitudes elicited by each stimulus were measured alternatively at 3 mm displacement loading and 5 g weight. Both the creatine/inorganic phosphate (PCr/Pi) and pH changes were more marked in direct electrical stimulation than in magnetic stimulation. The muscular contraction caused by magnetic stimulation showed less fatigue than that caused by direct electrical muscular stimulation.     

Effects of a draft-loaded interval-training program on skeletal muscle in the horse

Five Standardbred trotters were trained on a treadmill 3 times/wk for 12 wk by intervals of draft-loaded exercise. The draft load was 34 kp and the velocity approximately 7 m/s. Muscle biopsies were taken from the gluteus medius and longissimus muscles before training and after 2, 4, 8, and 12 wk of training and from the brachiocephalicus muscle before and after training. Both the percentage and the area of type IIa fibers increased and the percentage of type IIb fibers decreased in the gluteus medius muscle during the first 2 wk of training, and then no further significant difference was noted. The percentage of type I fibers increased in the brachiocephalicus muscle, and the area of type IIb fibers increased in the longissimus muscle. The citrate synthase activity increased in the gluteus muscle only, and the increase was seen during the first 2 wk. No significant differences were seen in 3-hydroxy-acyl-CoA dehydrogenase and lactate dehydrogenase activities in the muscles during the entire training period. Less glycogen was utilized in the gluteus muscle and less blood lactate accumulated when the horses performed an unloaded submaximal exercise test after compared with before training. It can be concluded that rapid changes are induced in the gluteus medius muscle when horses are trained pulling a light-draft resistance at a submaximal trotting speed.     

Dynamic exercise training in foxhounds. II. Analysis of skeletal muscle

The purpose of this study was to determine whether 8-12 wk of endurance training produces biochemical and histochemical adaptations in skeletal muscle in foxhounds. Analyses were performed on samples removed from gastrocnemius, triceps, and semitendinosus muscles of foxhounds before and after a treadmill running program. Biochemical analysis showed that training did not alter the activities of phosphofructokinase, beta-hydroxyacyl-CoA dehydrogenase, succinate dehydrogenase, or total phosphorylase. Histochemical analysis of myofibrillar actomyosin ATPase demonstrated three distinct classes of type II fibers and one type I fiber in the semitendinosus and triceps muscles and two type II and two type I fibers in the gastrocnemius muscle. Fiber type distribution and oxidative and glycolytic potentials, as indicated by nicotinamide adenine dinucleotide tetrazolium reductase or alpha-glycerophosphate dehydrogenase staining intensity, were unaltered by training. Similarly, capillary density, capillary-to-fiber ratios, and capillary area-to-fiber area ratios did not change with training. Thus, unlike humans and other mammals (i.e., rat), these foxhounds did not manifest biochemical or histochemical adaptations in skeletal muscle as the result of endurance training. This is consistent with the results of the study in which endurance training produced a 27% increase in maximal cardiac output and a 4% increase in maximal arteriovenous O2 extraction in foxhounds.     

Interactions of exercise training and ACE inhibition on insulin action in obese Zucker rats.

Exercise training or chronic treatment with angiotensin-converting enzyme (ACE) inhibitors can ameliorate glucose intolerance, insulin resistance of muscle glucose metabolism, and dyslipidemia associated with the obese Zucker rat. The purpose of the present study was to determine the interactions of exercise training and ACE inhibition (trandolapril) on these parameters in the obese Zucker rat. Animals were assigned to a sedentary control, a trandolapril-treated (1 mg. kg-1. day-1 for 6 wk), an exercise-trained (treadmill running for 6 wk), or a combined trandolapril-treated and exercise-trained group. Exercise training, alone or with trandolapril, significantly (P < 0. 05) increased peak O2 consumption by 31-34%. Similar decreases in fasting plasma insulin (34%) and free fatty acids (31%) occurred with exercise training alone or in combination with trandolapril. Compared with control, exercise training or trandolapril alone caused smaller areas under the curve (AUC) for glucose (12-14%) and insulin (28-33%) during an oral glucose tolerance test. The largest decreases in the glucose AUC (40%) and insulin AUC (53%) were observed in the combined group. Similarly, whereas exercise training or trandolapril alone improved maximally activated insulin-stimulated glucose transport in isolated epitrochlearis (26-34%) or soleus (39-41%) muscles, the greatest improvements in insulin action (67 and 107%, respectively) were seen in the combined group and were associated with similarly enhanced muscle GLUT-4 protein and total hexokinase levels. In conclusion, these results indicate combined exercise training and ACE inhibition improve oral glucose tolerance and insulin-stimulated muscle glucose transport to a greater extent than does either intervention alone.     

Capsiate Supplementation Reduces Oxidative Cost of Contraction in Exercising Mouse Skeletal Muscle In Vivo

Chronic administration of capsiate is known to accelerate whole-body basal energy metabolism, but the consequences in exercising skeletal muscle remain very poorly documented. In order to clarify this issue, the effect of 2-week daily administration of either vehicle (control) or purified capsiate (at 10- or 100-mg/kg body weight) on skeletal muscle function and energetics were investigated throughout a multidisciplinary approach combining in vivo and in vitro measurements in mice. Mechanical performance and energy metabolism were assessed strictly non-invasively in contracting gastrocnemius muscle using magnetic resonance (MR) imaging and 31-phosphorus MR spectroscopy (³¹P-MRS). Regardless of the dose, capsiate treatments markedly disturbed basal bioenergetics in vivo including intracellular pH alkalosis and decreased phosphocreatine content. Besides, capsiate administration did affect neither mitochondrial uncoupling protein-3 gene expression nor both basal and maximal oxygen consumption in isolated saponin-permeabilized fibers, but decreased by about twofold the K _m of mitochondrial respiration for ADP. During a standardized in vivo fatiguing protocol (6-min of repeated maximal isometric contractions electrically induced at a frequency of 1.7 Hz), both capsiate treatments reduced oxidative cost of contraction by 30-40%, whereas force-generating capacity and fatigability were not changed. Moreover, the rate of phosphocreatine resynthesis during the post-electrostimulation recovery period remained unaffected by capsiate. Both capsiate treatments further promoted muscle mass gain, and the higher dose also reduced body weight gain and abdominal fat content. These findings demonstrate that, in addition to its anti-obesity effect, capsiate supplementation improves oxidative metabolism in exercising muscle, which strengthen this compound as a natural compound for improving health.     

Effect of exercise training on tissue vitamin E and ubiquinone content

Endurance exercise training led to an adaptive increase in the ubiquinone content and cytochrome c reductase activity of red quadriceps and soleus muscles and adipose tissues, but not of cardiac or white quadriceps muscle. These findings are consistent with the well-known positive adaptation of skeletal muscle mitochondria to endurance training. However, there was no concomitant increase in the vitamin E content of tissues, which showed an increase in mitochondrial content. Since ubiquinone is located in the mitochondrial inner membrane and the major pool of vitamin E is also associated with mitochondrial membranes, the results suggest that training causes a substantial decrease in vitamin E concentration in the proliferating muscle mitochondrial membranes, thus depleting muscle mitochondria of their major lipid antioxidant. Since vitamin E is the major cellular, lipid-soluble, chain-breaking antioxidant, these findings indicate increased free radical reactions in the tissues of exercising animals.     

Regional body composition changes in women after 6 months of periodized physical training.

Data are lacking regarding regional morphological changes among women after prolonged physical training. This study employed dual-energy X-ray absorptiometry to assess changes in whole body and regional (i.e., trunk, legs, arms) fat mass, lean mass, and bone mineral content body composition adaptations in 31 healthy women pre-, mid-, and post-6 mo of periodized physical training. These results were compared with those of 1) a control group of women who had not undergone the training program and were assessed pre- and post-6 mo and 2) a group of 18 men that was tested only once. Additionally, magnetic resonance imaging was used to assess changes in muscle morphology of the thigh in a subset of 11 members of the training group. Physical training consisted of a combination of aerobic and resistance exercise in which the subjects engaged for 5 days/wk for 24 wk. Overall, the training group experienced a 2.2% decrease, a 10% decrease, and a 2.2% increase for body mass, fat mass, and soft tissue lean mass, respectively. No changes in bone mineral content were detected. The women had less of their soft tissue lean mass distributed in their arms than did the men, both before and after the women were trained. Novel to this study were the striking differences in the responses in the tissue composition of the arms (31% loss in fat mass but no change in lean mass) compared with the legs (5.5% gain in lean mass but no change in fat mass). There was a 12% fat loss in the trunk with no change in soft tissue lean mass. Dual-energy X-ray absorptiometry and magnetic resonance imaging fat mass measurements showed good agreement (r = 0. 72-0.92); their lean mass measurements were similar as well, showing approximately 5.5% increases in leg lean tissue. These findings show the importance of considering regional body composition changes, rather than whole body changes alone when assessing the effects of a periodized physical training program.     

Acute effect on power output of alternating an agonist and antagonist muscle exercise during complex training

The efficient coordination of agonist and antagonist muscles is one of the important early adaptations in resistance training responsible for large increases in strength. Weak antagonist muscles may limit speed of movement; consequently, strengthening them leads to an increase in agonist muscle movement speed. However, the effect of combining agonist and antagonist muscle exercises into a power training session has been largely unexplored. The purpose of this study was to determine if a training complex consisting of contrasting agonist and antagonist muscle exercises would result in an acute increase in power output in the agonist power exercise. Twenty-four college-aged rugby league players who were experienced in combined strength and power training served as subjects for this study. They were equally assigned to an experimental (Antag) or control (Con) group and were no different in age, height, body mass, strength, or maximal power. Power output was assessed during bench press throws with a 40-kg resistance (BT P40) with the Plyometric Power System training device. After warming up, the Con group performed the BT P40 tests 3 minutes apart to determine if any acute augmentation to power output could occur without intervention. The Antag group also performed the BT P40 tests; however, an intervention strategy of a set of bench pulls, which is an antagonistic action to the bench throw, was performed between tests to determine if this would acutely affect power output during the second BT P40 test. Although the power output for the Con group remained unaltered between test occasions, the significant 4.7% increase for the Antag group indicates that a strategy of alternating agonist and antagonist muscle exercises may acutely increase power output during complex power training. This result may affect power training and specific warm-up strategies used in ballistic sports activities, with increased emphasis placed upon the antagonist muscle groups.     

Analysis of phosphate metabolites, the intracellular pH, and the state of adenosine triphosphate in intact muscle by phosphorus nuclear magnetic resonance.

31P nuclear magnetic resonance spectra recorded from intact muophosphate, and the sugar phosphates. Quantitation of these metabolites by 31P nuclear magnetic resonance was in good agreement with values obtained by chemical analyses. The spectra obtained from various muscles showed considerable variation in their phosphorus profile. Thus, differences could be detected between (a) normal and diseased muscle; (b) vertebrates and invertebrates; (c) different species of the same animal. The time course of change in phosphate metabolites in frog muscle showed that ATP level remains unchanged until phosphocreatine is nearly depleted. Comparative studies revealed that under anaerobic conditions the Northern frog maintains its ATP content for 7 hours, while other types of amphibian, bird, and mammalian muscles begin to show an appreciable decay in ATP after 2 hours. Several lines of evidence indicated that ATP forms a complex with magnesium in the muscle water: (a) the phosphate resonances of ATP in the muscle were shifted downfield as compared to those in the alkaline earth metal-free perchloric acid extract of the muscle; (b) the coupling constants of ATP measured in various live muscles closely corresponded to those for MgATP in a solution resembling the composition of the muscle water; (c) in the muscle the gamma-phosphate group of ATP exhibited no shift change over a period of 10 hours under conditions where resonances of other phosphate compounds could be titrated. This behavior is similar to that of MgATP in model solutions in the physiological pH range, and it is different from that of CaATP. The chemical shifts of the phosphate metabolites were determined in several relevant solutions as a function of pH. Under all conditions only inorganic orthophosphate showed an invariant titration curve. From the chemical shift of inorganic phosphate observed during aging of intact muscle the intracellular pH of frog muscle was estimated to be 7.2.     

Phosphorus-31 magnetic resonance spectroscopy of forearm flexor muscles in student rowers using an exercise protocol adjusted for differences in cross-sectional muscle area

To assess exercise energy metabolism of forearm flexor muscles in rowers, six male student rowers and six control subjects matched for age and sex were studied using phosphorus-31 magnetic resonance spectroscopy (31P-MRS). Firstly, to adjust for the effect of differences in cross-sectional muscle area, the maximal cross-sectional area (CSAmax) of the forearm flexor muscles was estimated in each individual using magnetic resonance imaging. Multistage exercise was then carried out with an initial energy production of 1 J.cm-2 CSAmax for 1 min and an increment of 1 J.cm-2 CSAmax every minute to the point of muscle exhaustion. A series of measurements of 31P-MRS were performed every minute. The CSAmax was significantly greater in the student rowers than in the control subjects [19.8 (SD 2.2) vs 17.1 (SD 1.2) cm2, P less than 0.05]. The absolute maximal exercise intensity (J.min-1) was greater in the rowers than in the control subjects. However, the maximal exercise intensity per unit of muscle cross sectional area (J.min-1.cm-2) was not significantly different between the two groups. During mild to moderate exercise intensities, a decrease in phosphocreatine and an increase in inorganic phosphate before the onset of acidosis were significantly less in the rowers, indicating a requirement of less adenosine 5'-diphosphate to drive adenosine 5'-triphosphate production. The onset of acidosis was also significantly delayed in the rowers. No difference was observed in forearm blood flow between the two groups at the same exercise intensity (J.min-1.cm-2).(ABSTRACT TRUNCATED AT 250 WORDS)     

Biochemical adaptations to training: implications for resisting muscle fatigue

Skeletal muscle activity is invariably associated with a decline in force-generating capacity (fatigue). The build-up of metabolic by-products such as intracellular H+ and inorganic phosphate (Pi) has been shown to be one of the potential mechanisms of muscle fatigue. The use of phosphorus magnetic resonance spectroscopy is a repeatable and useful tool to study the effect of pH and Pi on force development. When maximal exercise is preceded by submaximal exercise to reduce the starting muscle pH and increase Pi, the degree of muscle fatigue correlates more strongly with H2PO4- than pH or Pi alone. However, other studies in humans have found that H2PO4- does not always correlate well with fatigue. The use of ramp exercise protocols allow repeatable and sensitive measurement of changes in muscle metabolism in response to endurance training. Chronic electrical stimulation in dogs and endurance training in humans results in reduced pH and Pi changes at the same exercise intensities. This means that the effect of pH and Pi in depressing force development is reduced, which could partially explain the increased fatigue resistance seen following endurance training.