Protein composition of endurance trained human skeletal muscle.

Evidence suggests that myofibers from endurance trained skeletal muscle display unique contractile parameters. However, the underlying mechanisms remain unclear. To further elucidate the influence of endurance training on myofiber contractile function, we examined factors that may impact myofilament interactions (i. e., water content, concentration of specific protein fractions, actin and myosin content) or directly modulate myosin heavy chain (MHC) function (i. e., myosin light chain (MLC) composition) in muscle biopsy samples from highly-trained competitive (RUN) and recreational (REC) runners. Muscle water content was lower (P<0.05) in RUN (73±1%) compared to REC (75±1%) and total muscle and myofibrillar protein concentration was higher (P<0.05) in RUN, which may indicate differences in myofilament spacing. Content of the primary contractile proteins, myosin (0.99±0.08 and 1.01±0.07 AU) and actin (1.33±0.09 and 1.27±0.09 AU) in addition to the myosin to actin ratio (0.75±0.04 and 0.80±0.06 AU) was not different between REC and RUN, respectively, when expressed relative to the amount of myofibrillar protein. At the single-fiber level, slow-twitch MHC I myofibers from RUN contained less (P<0.05) MLC 1 and greater (P<0.05) amounts of MLC 3 than REC, while MLC composition was similar in fast-twitch MHC IIa myofibers between REC and RUN. These data suggest that the distinctive myofiber contractile profile in highly-trained runners may be partially explained by differences in the content of the primary contractile proteins and provides unique insight into the modulation of contractile function with extreme loading -patterns.

Prostaglandin E2 induces transcription of skeletal muscle mass regulators interleukin-6 and muscle RING finger-1 in humans.

Cyclooxygenase (COX) inhibiting drugs augment muscle mass and strength improvements during resistance exercise based treatment of sarcopenia in older individuals. Initial evidence suggests a potential mechanism of COX inhibitor blunted prostaglandin (PG) E2 stimulation of interleukin (IL)-6 and the ubiquitin ligase MuRF-1, reducing their inhibition on muscle growth. The purpose of this investigation was to determine if PGE2 stimulates IL-6 and MuRF-1 transcription in skeletal muscle. Muscle biopsies were obtained from 10 young individuals and incubated ex vivo with PGE2 or control and analyzed for IL-6 and MuRF-1 mRNA levels. PGE2 upregulated (P<0.05) expression of both IL-6 (195%) and MuRF-1 (51%). A significant relationship was found between IL-6 and MuRF-1 expression after incubation with PGE2 (r=0.77, P<0.05), suggesting regulation through a common pathway. PGE2 induces IL-6 and MuRF-1 transcription in human skeletal muscle, providing a mechanistic link between COX inhibiting drugs, PGE2, and the regulation of muscle mass.

Influence of aerobic cycle exercise training on patellar tendon cross-sectional area in older women.

Nine to 12 weeks of resistance exercise training in young individuals induces quadriceps muscle (∼6%) and region-specific patellar tendon (4-6%) hypertrophy. However, 12 weeks of resistance exercise training (∼1 h total exercise time) in older individuals (60-78 years) induces quadriceps muscle hypertrophy (9%) without impacting patellar tendon size. The current study examined if a different loading paradigm using cycle exercise would promote patellar tendon hypertrophy or alter the internal tendon properties, measured with magnetic resonance imaging signal intensity, in older individuals. Nine women (70 ± 2 years) completed 12 weeks of aerobic upright cycle exercise training (∼28 h total exercise time). Aerobic exercise training increased (P < 0.05) quadriceps muscle size (11 ± 2%) and VO2max (30 ± 9%). Mean patellar tendon cross-sectional area (CSA) (2 ± 1%) and signal intensity (-1 ± 2%) were unchanged (P > 0.05) over the 12 weeks of training. Region-specific CSA was unchanged (P > 0.05) at the proximal (-1 ± 3%) and mid regions (2 ± 2%) of the tendon but tended (P = 0.069) to increase at the distal region (5 ± 3%). Region-specific signal intensity differed along the tendon but was unchanged (P > 0.05) with training. Although more studies are needed, exercise-induced patellar tendon hypertrophy, compared with skeletal muscle, appears to be attenuated in older individuals, while the loading pattern associated with aerobic exercise seems to have more impact than resistance exercise in promoting patellar tendon hypertrophy.

Influence of acetaminophen and ibuprofen on in vivo patellar tendon adaptations to knee extensor resistance exercise in older adults.

Millions of older individuals consume acetaminophen or ibuprofen daily and these same individuals are encouraged to participate in resistance training. Several in vitro studies suggest that cyclooxygenase-inhibiting drugs can alter tendon metabolism and may influence adaptations to resistance training. Thirty-six individuals were randomly assigned to a placebo (67 ± 2 yr old), acetaminophen (64 ± 1 yr old; 4,000 mg/day), or ibuprofen (64 ± 1 yr old; 1,200 mg/day) group in a double-blind manner and completed 12 wk of knee extensor resistance training. Before and after training in vivo patellar tendon properties were assessed with MRI [cross-sectional area (CSA) and signal intensity] and ultrasonography of patellar tendon deformation coupled with force measurements to obtain stiffness, modulus, stress, and strain. Mean patellar tendon CSA was unchanged (P > 0.05) with training in the placebo group, and this response was not influenced with ibuprofen consumption. Mean tendon CSA increased with training in the acetaminophen group (3%, P < 0.05), primarily due to increases in the mid (7%, P < 0.05) and distal (8%, P < 0.05) tendon regions. Correspondingly, tendon signal intensity increased with training in the acetaminophen group at the mid (13%, P < 0.05) and distal (15%, P = 0.07) regions. When normalized to pretraining force levels, patellar tendon deformation and strain decreased 11% (P < 0.05) and stiffness, modulus, and stress were unchanged (P > 0.05) with training in the placebo group. These responses were generally uninfluenced by ibuprofen consumption. In the acetaminophen group, tendon deformation and strain increased 20% (P < 0.05) and stiffness (-17%, P < 0.05) and modulus (-20%, P < 0.05) decreased with training. These data suggest that 3 mo of knee extensor resistance training in older adults induces modest changes in the mechanical properties of the patellar tendon. Over-the-counter doses of acetaminophen, but not ibuprofen, have a strong influence on tendon mechanical and material property adaptations to resistance training. These findings add to a growing body of evidence that acetaminophen has profound effects on peripheral tissues in humans.

Effects of 3 days unloading on molecular regulators of muscle size in humans.

Changes in skeletal muscle mass are controlled by mechanisms that dictate protein synthesis or degradation. The current human study explored whether changes in activation of the phosphoinositide 3-kinase (PI3K)-Akt1, p38, myostatin, and mRNA expression of markers of protein degradation and synthesis occur soon after withdrawal of weight bearing. Biopsies of the vastus lateralis muscle (VL) and soleus muscle (Sol) were obtained from eight healthy men before and following 3 days of unilateral lower limb suspension (ULLS). Akt1, Forkhead box class O (FOXO)-1A, FOXO-3A, p38, and eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1) phosphorylation and protein levels and myostatin protein level were analyzed by Western blot. Levels of mRNA of IGF1, FOXO-1A, FOXO-3A, atrogin-1, MuRF-1, caspase-3, calpain-2, calpain-3, 4E-BP1, and myostatin were measured using real-time PCR. The amounts of phosphorylated Akt1, FOXO-1A, FOXO-3A, and p38 were unaltered (P>0.05) after ULLS. Similarly, mRNA levels of IGF1, FOXO-1A, FOXO-3A, caspase-3, calpain-2, and calpain-3 showed no changes (P>0.05). The mRNA levels of atrogin-1 and MuRF-1, as well as the mRNA and protein phosphorylation of 4E-BP1, increased (P<0.05) in VL but not in Sol. Both muscles showed increased (P<0.05) myostatin mRNA and protein following ULLS. These results suggest that pathways other than PI3K-Akt stimulate atrogin-1 and MuRF-1 expression within 3 days of ULLS. Alternatively, transient changes in these pathways occurred in the early phase of ULLS. The increased myostatin mRNA and protein expression also indicate that multiple processes are involved in the early phase of muscle wasting. Further, the reported difference in gene expression pattern across muscles suggests that mechanisms regulating protein content in human skeletal muscle are influenced by phenotype and/or function.

A new method to study in vivo protein synthesis in slow- and fast-twitch muscle fibers and initial measurements in humans.

The aim of this study was to develop an approach to directly assess protein fractional synthesis rate (FSR) in isolated human muscle fibers in a fiber type-specific fashion. Individual muscle fibers were isolated from biopsies of the vastus lateralis (VL) and soleus (SOL) obtained from eight young men during a primed, continuous infusion of [5,5,5-(2)H3]leucine performed under basal conditions. To determine mixed protein FSR, a portion of each fiber was used to identify fiber type, fibers of the same type were pooled, and the [5,5,5-(2)H3]leucine enrichment was determined via GC-MS. Processing isolated slow-twitch [myosin heavy chain (MHC) I] and fast-twitch (MHC IIa) fibers for mixed protein bound [5,5,5-(2)H3]leucine enrichment yielded mass ion chromatographic peaks that were similar in shape, abundance, and measurement reliability as tissue homogenates. In the VL, MHC I fibers exhibited a 33% faster (P<0.05) mixed protein FSR compared with MHC IIa fibers (0.068+/-0.006 vs. 0.051+/-0.003%/h). MHC I fibers from the SOL (0.060+/-0.005%/h) and MHC I fibers from the VL displayed similar (P>0.05) mixed protein FSR. Feasibility of processing isolated human muscle fibers for analysis of myofibrillar protein [5,5,5-(2)H3]leucine enrichment was also confirmed in non-fiber-typed pooled fibers from the VL. These methods can be applied to the study of fiber type-specific responses in human skeletal muscle. The need for this level of investigation is underscored by the different contributions of each fiber type to whole muscle function and the numerous distinct adaptive functional and metabolic changes in MHC I and MHC II fibers originating from the same muscle.

Influence of aging on the in vivo properties of human patellar tendon.

Tendons are important for optimal muscle force transfer to bone and play a key role in functional ability. Changes in tendon properties with aging could contribute to declines in physical function commonly associated with aging. We investigated the in vivo mechanical properties of the patellar tendon in 37 men and women [11 young (27 +/- 1 yr) and 26 old (65 +/- 1 yr)] using ultrasonography and magnetic resonance imaging (MRI). Patella displacement relative to the tibia was monitored with ultrasonography during ramped isometric contractions of the knee extensors, and MRI was used to determine tendon cross-sectional area (CSA) and signal intensity. At peak force, patellar tendon deformation, stress, and strain were 13 (P = 0.05), 19, and 12% less in old compared with young (P < 0.05). Additionally, deformation, stiffness, stress, CSA, and length were 18, 35, 41, 28, and 11% greater (P < 0.05), respectively, in men compared with women. After normalization of mechanical properties to a common force, no age differences were apparent; however, stress and strain were 26 and 22% higher, respectively, in women compared with men (P < 0.05). CSA and signal intensity decreased 12 and 24%, respectively, with aging (P < 0.05) in the midregion of the tendon. These data suggest that differences in patellar tendon in vivo mechanical properties with aging are more related to force output rather than an age effect. In contrast, the decrease in signal intensity indirectly suggests that the internal milieu of the tendon is altered with aging; however, the physiological and functional consequence of this finding requires further study.

Resistance exercise reduces muscular substrates in women.

The purpose of this investigation was to examine the influence of an acute bout of resistance exercise (RE) on intramuscular triglyceride (IMTG) and muscle glycogen concentrations and intracellular signaling in women with high body fat content. Six overweight women with a high percent body fat (age 29+/-3 yr; BMI 28+/-3 kg/m(2), body fat 38+/-4%) performed 6 sets of 10 repetitions of knee extension exercise at 70% 1RM. Muscle biopsies were obtained from the vastus lateralis before, 1 min after (POST1), and 2 h after (POST2) exercise. Acute RE reduced (p<0.05) IMTG content approximately 40% at POST1 and POST2 (75+/-5; 45+/-6; 50+/-10 mmol/kg/dry wt). Muscle glycogen was also reduced (p<0.05) approximately 25% at POST1 and remained lower at POST2 (317+/-14; 241+/-30; 235+/-26 mmol/kg/dry wt). ERK1/2, SAPK/JNK, and p38 phosphorylation were increased (p<0.05) approximately 2-3-fold at POST1 and ERK1/2 remained elevated and POST2 whereas SAPK/JNK and p38 returned to basal levels. AMPKalpha phosphorylation was unchanged in response to RE. These results show that both IMTG and muscle glycogen stores serve as an important energy source during RE in overweight women and the MAP kinase signaling response to RE is not compromised by high levels of body fat.

Influence of concurrent exercise or nutrition countermeasures on thigh and calf muscle size and function during 60 days of bed rest in women.

AIM: The goal of this investigation was to test specific exercise and nutrition countermeasures to lower limb skeletal muscle volume and strength losses during 60 days of simulated weightlessness (6 degrees head-down-tilt bed rest). METHODS: Twenty-four women underwent bed rest only (BR, n = 8), bed rest and a concurrent exercise training countermeasure (thigh and calf resistance training and aerobic treadmill training; BRE, n = 8), or bed rest and a nutrition countermeasure (a leucine-enriched high protein diet; BRN, n = 8). RESULTS: Thigh (quadriceps femoris) muscle volume was decreased (P < 0.05) in BR (-21 +/- 1%) and BRN (-24 +/- 2%), with BRN losing more (P < 0.05) than BR. BRE maintained (P > 0.05) thigh muscle volume. Calf (triceps surae) muscle volume was decreased (P < 0.05) to a similar extent (P > 0.05) in BR (-29 +/- 1%) and BRN (-28 +/- 1%), and this decrease was attenuated (P < 0.05) in BRE (-8 +/- 2%). BR and BRN experienced large (P < 0.05) and similar (P > 0.05) decreases in isometric and dynamic (concentric force, eccentric force, power and work) muscle strength for supine squat (-19 to -33%) and calf press (-26 to -46%). BRE maintained (P > 0.05) or increased (P < 0.05) all measures of muscle strength. CONCLUSION: The nutrition countermeasure was not effective in offsetting lower limb muscle volume or strength loss, and actually promoted thigh muscle volume loss. The concurrent aerobic and resistance exercise protocol was effective at preventing thigh muscle volume loss, and thigh and calf muscle strength loss. While the exercise protocol offset approximately 75% of the calf muscle volume loss, modification of this regimen is needed.

Resistance exercise and cyclooxygenase (COX) expression in human skeletal muscle: implications for COX-inhibiting drugs and protein synthesis.

We have shown that ibuprofen and acetaminophen block cyclooxygenase (COX) synthesis of prostaglandin PGF(2alpha) and the muscle protein synthesis increase following resistance exercise. Confusingly, these two drugs are purported to work through different mechanisms, with acetaminophen apparently unable to block COX and ibuprofen able to nonspecifically block COX-1 and COX-2. A recently discovered intron-retaining COX, now known to have three variants, has been shown to be sensitive to both drugs. We measured the expression patterns and levels of the intron 1-retaining COX-1 variants (-1b1, -1b2, and -1b3), COX-1, and COX-2 at rest and following resistance exercise to help elucidate the COX through which PGF(2alpha), ibuprofen, and acetaminophen regulate muscle protein synthesis. Skeletal muscle biopsy samples were taken from 16 individuals (8M, 8F) before, 4, and 24 h after a bout of resistance exercise and analyzed using real-time RT-PCR. Relatively few individuals expressed the intron 1-retaining COX-1b variants (COX-1b1, -1b2, and -1b3) at any time point, and when expressed, these variants were in very low abundance. COX-1 was the most abundant COX mRNA before exercise and remained unchanged (P > 0.05) following exercise. COX-2 was not expressed before exercise, but increased significantly (P < 0.05) at 4 and 24 h after exercise. The inconsistent and low levels of expression of the intron 1-retaining COX-1 variants suggest that these variants are not likely responsible for the inhibition of PGF(2alpha) production and skeletal muscle protein synthesis after resistance exercise by ibuprofen and acetaminophen. Skeletal muscle-specific inhibition of COX-1 or COX-2 by these drugs should be considered.

The effect of strenuous aerobic exercise on skeletal muscle myofibrillar proteolysis in humans.

Relatively little is known about the dynamics of the skeletal muscle protein pool following aerobic exercise. Myofibrillar protein synthesis has recently been shown to be substantially elevated for 3 days after a strenuous 60 min bout of one-legged aerobic exercise, and this increase was surprisingly equal to or greater than what has been shown numerous times following resistance exercise over the same time course. Because net protein accretion is the sum of protein synthesis and degradation, we sought to directly measure skeletal muscle myofibrillar proteolysis in five healthy young males in response to an identical strenuous 60 min aerobic exercise bout and at the same time points (rest, 6, and 24 h post-exercise and 48 and 72 h post-exercise in a subset of subjects). We measured skeletal muscle myofibrillar proteolysis by monitoring the release of the natural tracer 3-methylhistidine (3MH) from the vastus lateralis muscle into the interstitial space via microdialysis. Skeletal muscle interstitial 3MH concentration was no different (P>0.05) from rest (5.16+/-0.38 nmol/mL) after 6 (5.37+/-0.55 nmol/mL), 24 (5.40+/-0.26 nmol/mL), 48 (5.50+/-0.74 nmol/mL), or 72 h (4.73+/-0.28 nmol/mL). These results suggest that proteolysis of the myofibrillar fraction of skeletal muscle is relatively refractory to an intense aerobic exercise stimulus for up to 3 days, despite the large increase in synthesis of this muscle fraction following the same exercise stimulus. The apparent net myofibrillar protein accretion in the hours and days after exercise may occur in order to offset the large elevation in mixed muscle proteolysis that has been shown during similar bouts of intense one-legged aerobic exercise.

Human soleus muscle protein synthesis following resistance exercise.

AIM: It is generally believed the calf muscles in humans are relatively unresponsive to resistance training when compared with other muscles of the body. The purpose of this investigation was to determine the muscle protein synthesis response of the soleus muscle following a standard high intensity bout of resistance exercise. METHODS: Eight recreationally active males (27 +/- 4 years) completed three unilateral calf muscle exercises: standing calf press/heel raise, bent-knee calf press/heel raise, and seated calf press/heel raise. Each exercise consisted of four sets of 15 repetitions (approximately 15 repetition maximum, RM, or approximately 70% 1RM). Fractional rate of muscle protein synthesis (FSR) was determined with a primed constant infusion of [2H5]phenylalanine coupled with muscle biopsies immediately and 3 h following the exercise in both the exercise and non-exercise (resting control) leg. RESULTS: FSR was elevated (P < 0.05) in the exercise (0.069 +/- 0.010) vs. the control (0.051 +/- 0.012) leg. Muscle glycogen concentration was lower (P < 0.05) in the exercise compared with the control leg (Decrease from control; immediate post-exercise: 54 +/- 5; 3 h post-exercise: 36 +/- 4 mmol kg(-1) wet wt.). This relatively high amount of glycogen use is comparable with previous studies of resistance exercise of the thigh (i.e. vastus lateralis; approximately 41-49 mmol kg(-1) wet wt.). However, the exercise-induced increase in FSR that has been consistently reported for the vastus lateralis (approximately 0.045-0.060% h(-1)) is on average approximately 200% higher than reported here for the soleus (0.019 +/- 0.003% h(-1)). CONCLUSIONS: These results suggest the relatively poor response of soleus muscle protein synthesis to an acute bout of resistance exercise may be the basis for the relative inability of the calf muscles to respond to resistance training programs.

Effect of ibuprofen and acetaminophen on postexercise muscle protein synthesis.

We examined the effect of two commonly consumed over-the-counter analgesics, ibuprofen and acetaminophen, on muscle protein synthesis and soreness after high-intensity eccentric resistance exercise. Twenty-four males (25 +/- 3 yr, 180 +/- 6 cm, 81 +/- 6 kg, and 17 +/- 8% body fat) were assigned to one of three groups that received either the maximal over-the-counter dose of ibuprofen (IBU; 1,200 mg/day), acetaminophen (ACET; 4,000 mg/day), or a placebo (PLA) after 10-14 sets of 10 eccentric repetitions at 120% of concentric one-repetition maximum with the knee extensors. Postexercise (24 h) skeletal muscle fractional synthesis rate (FSR) was increased 76 +/- 19% (P < 0.05) in PLA (0.058 +/- 0.012%/h) and was unchanged (P > 0.05) in IBU (35 +/- 21%; 0.021 +/- 0.014%/h) and ACET (22 +/- 23%; 0.010 +/- 0.019%/h). Neither drug had any influence on whole body protein breakdown, as measured by rate of phenylalanine appearance, on serum creatine kinase, or on rating of perceived muscle soreness compared with PLA. These results suggest that over-the-counter doses of both ibuprofen and acetaminophen suppress the protein synthesis response in skeletal muscle after eccentric resistance exercise. Thus these two analgesics may work through a common mechanism to influence protein metabolism in skeletal muscle.

The influence of 5 weeks of ULLS and resistance exercise on vastus lateralis and soleus myosin heavy chain distribution.

We examined the distribution of the myosin heavy chain (MHC) isoforms (I, IIa, IIx) of the leg muscles of three groups of men and women (40 +/- 8y) that completed unilateral lower limb suspension only (ULLS), ULLS plus resistance exercise (ULLS+RE), or RE only (RE) for 5 weeks. Muscle biopsies were obtained pre and post from the vastus lateralis of all three groups and the soleus of the ULLS group. Distributions of all three MHC isoforms in the vastus lateralis were unchanged (p<0.05) from pre to post with ULLS. The soleus muscle, which contained no measurable IIx isoform, was also unchanged (p< 0.05) from pre to post ULLS. These results suggest that the percent distribution of the MHC isoforms per unit muscle protein in both the vastus lateralis and soleus does not change during the first five weeks of simulated microgravity. Further, resistance exercise during five weeks of ULLS or ambulation does not appear to alter the MHC distribution per unit muscle protein of the vastus lateralis.

Skeletal muscle protein composition following 5 weeks of ULLS and resistance exercise countermeasures.

The effects of 5 weeks of unilateral lower limb suspension (ULLS) and flywheel resistance exercise (RE) on skeletal muscle protein composition were examined in thirty-one subjects (40 +/- 8y), divided into three groups: ULLS, ULLS+RE, and RE. Pre and post biopsy samples were examined for protein concentration, myosin heavy chain (MHC) and actin concentration. VL protein concentration of the three groups did not change. Soleus protein concentration following ULLS decreased (p<0.05). MHC and actin content of the VL and soleus were unaltered. Muscle mass changed from pre to post: ULLS -11% (VL), -11% (soleus), both p<0.05; ULLS+RE +9%, p<0.05; RE +6%, P<0.05. Therefore, the increase or decrease in VL muscle mass over 5 weeks occurred while maintaining protein, MHC and actin. However, soleus muscle atrophy occurred at the expense of other muscle proteins, since MHC and actin were maintained and protein concentrations decreased.

Skeletal muscle PGF(2)(alpha) and PGE(2) in response to eccentric resistance exercise: influence of ibuprofen acetaminophen.

PGs have been shown to modulate skeletal muscle protein metabolism as well as inflammation and pain. In nonskeletal muscle tissues, the over the counter analgesic drugs ibuprofen and acetaminophen function through suppression of PG synthesis. We previously reported that ibuprofen and acetaminophen inhibit the normal increase in skeletal muscle protein synthesis after high intensity eccentric resistance exercise. The current study examined skeletal muscle PG levels in the same subjects to further investigate the mechanisms of action of these drugs in exercised skeletal muscle. Twenty-four males (25 +/- 3 yr) were assigned to 3 groups that received the maximal over the counter dose of ibuprofen (1200 mg/d), acetaminophen (4000 mg/d), or a placebo after 10-14 sets of 10 eccentric repetitions at 120% of concentric 1 repetition maximum using the knee extensors. Preexercise and 24 h postexercise biopsies of the vastus lateralis revealed that the exercise-induced change in PGF(2alpha) in the placebo group (77%) was significantly different (P < 0.05) from those in the ibuprofen (-1%) and acetaminophen (-14%) groups. However, the exercise-induced change in PGE(2) in the placebo group (64%) was only significantly different (P < 0.05) from that in the acetaminophen group (-16%). The exercise-induced changes in PGF(2alpha) and PGE(2) were not different between the ibuprofen and acetaminophen groups. These results suggest that ibuprofen and acetaminophen have a comparable effect on suppressing the normal increase in PGF(2alpha) in human skeletal muscle after eccentric resistance exercise, which may profoundly influence the anabolic response of muscle to this form of exercise.

Short-term moderate weight loss and resistance training do not affect insulin-stimulated glucose disposal in postmenopausal women.

OBJECTIVES: Moderate weight loss and exercise have been proposed as important tools in the treatment and prevention of type 2 diabetes. Therefore, we tested the hypothesis that short-term (4 weeks) moderate energy restriction (-750 kcal/day) would result in a significant increase in insulin-stimulated glucose disposal (40 mU x m(-2) x min(-1) hyperinsulinemic-euglycemic clamp) in moderately overweight postmenopausal women and that when combined with resistance training (RT) an even greater effect would be seen. RESEARCH DESIGN AND METHODS: Older women were randomly assigned to energy restriction (WLoss group; n = 9) or energy restriction plus RT (RT + WLoss group; n = 10). RESULTS: For the WLoss versus the RT + WLoss groups, changes in body weight (-3.0 +/- 0.2 kg vs. -3.2 +/- 0.3 kg), fat mass (FM) (-3.0 +/- 0.3 kg vs. -3.2 +/- 0.3 kg), and percent body fat (BF) (-2.1 +/- 0.4 vs. -2.4 +/- 0.3%) were not different between groups. Muscle mass (group-by-time interaction, P = 0.04) was preserved in RT + WLoss (0.40 +/- 0.40 kg) and reduced in WLoss (-0.64 +/- 0.18 kg). There were no changes in fat-free mass (FFM) and waist-to-hip ratio in either group. Whole body glucose disposal (WLoss 6.14 +/- 0.57 vs. 6.03 +/- 0.53, RT + WLoss 5.85 +/- 0.60 vs. 6.09 +/- 0.56 mg/kg of FFM/min) did not change in either group. CONCLUSIONS: The results of this study demonstrate that short-term energy restriction resulting in moderate decreases in body weight (4.0 +/- 0.3%) and FM (8.2 +/- 0.7%) did not improve insulin-stimulated glucose disposal. The addition of RT to the hypoenergetic diet preserved muscle mass but provided no synergistic effect on insulin action. These results suggest that a greater change in body weight or FM may be necessary to observe a significant improvement in insulin action.

Comparison of a space shuttle flight (STS-78) and bed rest on human muscle function.

The purpose of this investigation was to assess muscle fiber size, composition, and in vivo contractile characteristics of the calf muscle of four male crew members during a 17-day spaceflight (SF; Life and Microgravity Sciences Spacelab Shuttle Transport System-78 mission) and eight men during a 17-day bed rest (BR). The protocols and timelines of these two investigations were identical, therefore allowing for direct comparisons between SF and the BR. The subjects' age, height, and weight were 43 +/- 2 yr, 183 +/- 4 cm, and 86 +/- 3 kg for SF and 43 +/- 2 yr, 182 +/- 3 cm, and 82 +/- 4 kg for BR, respectively. Calf muscle strength was examined before SF and BR; on days 2, 8, and 12 during SF and BR; and on days 2 and 8 of recovery. Muscle biopsies were obtained before and within 3 h after SF (gastrocnemius and soleus) and BR (soleus) before reloading. Maximal isometric calf strength and the force-velocity characteristics were unchanged with SF or BR. Additionally, neither SF nor BR had any effect on fiber composition or fiber size of the calf muscles studied. In summary, no changes in calf muscle strength and morphology were observed after the 17-day SF and BR. Because muscle strength is lost during unloading, both during spaceflight and on the ground, these data suggest that the testing sequence employed during the SF and BR may have served as a resistance training countermeasure to attenuate whole muscle strength loss.

Calf muscle strength in humans.

In an effort to measure strength characteristics of the calf muscles, 18 subjects (14 male, 4 female, age =34.3+/-2.4yrs) were tested using a specially designed torque velocity device (TVD). This TVD is a hardware interface with the subject's lower leg which stabilizes the leg for calf muscle strength measurements. Calf muscle strength measurements consisted of 1) isometric force production at ankle angles of 80, 90, and 100 degrees of plantar flexion, 2) peak torque at six isokinetic angular velocities 0.52, 1.05, 2.09, 3.14, 4.19, and 5.24 rad x s(-1), and 3) a fatigue test consisting of 30 maximal contractions at 3.14 rad x s(-1). The greatest force production occurred at 80 degrees of ankle plantar flexion (148.5 +/- 40.2 Nm). Isokinetic force production ranged from 114.1 +/- 24.7 Nm at 0.52 rad x s(-1) to 16.8 +/- 6.5 Nm at 5.24 rad x s(-1). A fatigue test consisting of 30 maximal repetitions at 3.14 rad x s(-1) resulted in a 61 +/- 15% decline in force production. To assess reproducibility and day to day variation, measurements at 1.05 and 2.09 rad x s(-1) were made during five different trials in a single day and one trial per day for three days, respectively. The within subject coefficient of variation was 2.6 to 6.5% for reproducibility and 1.9 to 7.4% for day to day variation. Magnetic resonance imaging (MRI) of the lower limb and muscle biopsy specimens from the gastrocnemius (lateral head) and soleus muscles were obtained to examine the relationship between strength and morphological characteristics of the calf muscles. Cross-sectional area of the primary plantar flexors (gastrocnemius and soleus) was 47.9 +/- 1.3 cm2 while muscle volume was 642 +/- 16 cm3. Muscle fiber composition of the gastrocnemius and soleus averaged 57 +/- 2 and 85 +/- 3% type I fibers, respectively. A poor correlation was found between fiber type and maximal isometric force production (r =0.38; p>0.05). However, calf muscle strength and muscle size was positively correlated (r = 0.76; p < 0.05). These data indicate that using the TVD interface to stabilize the lower leg is a reliable and reproducible procedure for the measurement of calf muscle strength.

Muscle-specific atrophy of the quadriceps femoris with aging.

We examined the size of the four muscles of the quadriceps femoris in young and old men and women to assess whether the vastus lateralis is an appropriate surrogate for the quadriceps femoris in human studies of aging skeletal muscle. Ten young (24 +/- 2 yr) and ten old (79 +/- 7 yr) sedentary individuals underwent magnetic resonance imaging of the quadriceps femoris after 60 min of supine rest. Volume (cm3) and average cross-sectional area (CSA, cm2) of the rectus femoris (RF), vastus lateralis (VL), vastus intermedius (VI), vastus medialis (VM), and the total quadriceps femoris were decreased (P < 0.05) in older compared with younger women and men. However, percentage of the total quadriceps femoris taken up by each muscle was similar (P > 0.05) between young and old (RF: 10 +/- 0.3 vs. 11 +/- 0.4; VL: 33 +/- 1 vs. 33 +/- 1; VI: 31 +/- 1 vs. 31 +/- 0.4; VM: 26 +/- 1 vs. 25 +/- 1%). These results suggest that each of the four muscles of the quadriceps femoris atrophy similarly in aging men and women. Our data support the use of vastus lateralis tissue to represent the quadriceps femoris muscle in aging research.