Proteolytic mRNA expression in response to acute resistance exercise in human single skeletal muscle fibers.
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The purpose of this study was to characterize changes in mRNA expression of select proteolytic markers in human slow-twitch [myosin heavy chain (MHC) I] and fast-twitch (MHC IIa) single skeletal muscle fibers following a bout of resistance exercise (RE). Muscle biopsies were obtained from the vastus lateralis of eight young healthy sedentary men [23 +/- 2 yr (mean +/- SD), 93 +/- 17 kg, 183 +/- 6 cm] before and 4 and 24 h after 3 x 10 repetitions of bilateral knee extensions at 65% of one repetition maximum. The mRNA levels of TNF-alpha, calpains 1 and 2, muscle RING (really interesting novel gene) finger-1 (MuRF-1), atrogin-1, caspase-3, B-cell leukemia/lymphoma (Bcl)-2, and Bcl-2-associated X protein (Bax) were quantified using real-time RT-PCR. Generally, MHC I fibers had higher (1.6- to 5.0-fold, P < 0.05) mRNA expression pre- and post-RE. One exception was a higher (1.6- to 3.9-fold, P < 0.05) Bax-to-Bcl-2 mRNA ratio in MHC IIa fibers pre- and post-RE. RE increased (1.4- to 4.8-fold, P < 0.05) MuRF-1 and caspase-3 mRNA levels 4-24 h post-RE in both fiber types, whereas Bax-to-Bcl-2 mRNA ratio increased 2.2-fold (P < 0.05) at 4 h post-RE only in MHC I fibers. These results suggest that MHC I fibers have a greater proteolytic mRNA expression pre- and post-RE compared with MHC IIa fibers. The greatest mRNA induction following RE was in MuRF-1 and caspase-3 in both fiber types. This altered and specific proteolytic mRNA expression among slow- and fast-twitch muscle fibers indicates that the ubiquitin/proteasomal and caspase pathways may play an important role in muscle remodeling with RE. (+info)
GRB14, GPD1, and GDF8 as potential network collaborators in weight loss-induced improvements in insulin action in human skeletal muscle.
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Obesity is associated with insulin resistance in skeletal muscle; accordingly, weight loss dramatically improves insulin action. We sought to identify molecular remodeling of muscle commensurate with weight loss that could explain improvements in insulin action. Muscle from morbidly obese women was studied before and after gastric bypass surgery. Gastric bypass surgery significantly reduced body mass by approximately 45% and improved insulin action. We then assessed mRNA profiles using a stringent statistical analysis (statistical concordance with three probe set algorithms), with validation in a cross-sectional study of lean (n = 8) vs. morbidly obese (n = 8) muscle. Growth factor receptor-bound protein 14 (GRB14), glycerol-3-phosphate dehydrogenase 1 (GPD1), and growth differentiation factor 8 (GDF8; myostatin) significantly decreased approximately 2.4-, 2.2-, and 2.4-fold, respectively, after weight loss (gastric bypass). Increased expression of these transcripts was associated with increased obesity in the cross-sectional group (lean vs. morbidly obese muscle). Each transcript was validated by real-time quantitative RT-PCR assays in both study groups. Using Ingenuity Pathway Analysis, we show that all three transcripts are involved in the same regulatory network including AKT1, IGF1, TNF, PPARG, and INS. These results suggest that GRB14, GPD1, and GDF8 are weight loss-responsive genes in skeletal muscle and that the observed transcriptional modulation of these would be expected to improve insulin signaling, decrease triglyceride synthesis, and increase muscle mass, respectively, with weight loss. Thus our data provide a possible regulatory pathway involved in the development of insulin resistance in the morbidly obese state, and improvement of insulin resistance with weight loss. (+info)
Different changes of quantity due to aging in the psoas major and quadriceps femoris muscles in women.
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Bone fractures cause disabilities that leave the elderly bedridden and strengthening the muscles of the lower limbs, especially the quadriceps femoris, is the main kinematical method of preventing falls. Recently, however, it has become clear that the psoas major is critical for walking ability. We examined changes due to aging in the size of the psoas major compared with changes in the quadriceps femoris. Bone fractures are more frequent in women than in men; our participants (n=210) were therefore exclusively women ranging in age from 20 to 79 and divided into 6 age groups (n=35 each) in 10-year increments. Cross-sectional areas of the two muscles were measured by an MR scanner for a comparative estimation of muscle size. The psoas major showed the greatest quantity in subjects in their 20s, after which it declined steadily until the 60s and dramatically in the 70s, while the area of the quadriceps femoris was preserved until the 40s and showed no dramatic later decline. Exercise beyond regular daily activities is recommended to prevent the psoas major from decreasing in volume. We also recommend the development of a method of maintaining its muscle volume which would target women younger than 40 and older than 60. (+info)
Insulin resistance does not influence gene expression in skeletal muscle.
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Insulin resistance is commonly observed in patients prior to the development of type 2 diabetes and may predict the onset of the disease. We tested the hypothesis that impairment in insulin stimulated glucose-disposal in insulin resistant patients would be reflected in the gene expression profile of skeletal muscle. We performed gene expression profiling on skeletal muscle of insulin resistant and insulin sensitive subjects using microarrays. Microarray analysis of 19,000 genes in skeletal muscle did not display a significant difference between insulin resistant and insulin sensitive muscle. This was confirmed with real-time PCR. Our results suggest that insulin resistance is not reflected by changes in the gene expression profile in skeletal muscle. (+info)
Skeletal muscle and heart LKB1 deficiency causes decreased voluntary running and reduced muscle mitochondrial marker enzyme expression in mice.
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LKB1 has been identified as a component of the major upstream kinase of AMP-activated protein kinase (AMPK) in skeletal muscle. To investigate the roles of LKB1 in skeletal muscle, we used muscle-specific LKB1 knockout (MLKB1KO) mice that exhibit low expression of LKB1 in heart and skeletal muscle, but not in other tissues. The importance of LKB1 in muscle physiology was demonstrated by the observation that electrical stimulation of the muscle in situ increased AMPK phosphorylation and activity in the wild-type (WT) but not in the muscle-specific LKB1KO mice. Likewise, phosphorylation of acetyl-CoA carboxylase (ACC) was markedly attenuated in the KO mice. The LKB1KO mice had difficulty running on the treadmill and exhibited marked reduction in distance run in voluntary running wheels over a 3-wk period (5.9 +/- 0.9 km/day for WT vs. 1.7 +/- 0.7 km/day for MLKB1KO mice). The MLKB1KO mice anesthetized at rest exhibited significantly decreased phospho-AMPK and phospho-ACC compared with WT mice. KO mice exhibited lower levels of mitochondrial protein expression in the red and white regions of the quadriceps. These observations, along with previous observations from other laboratories, clearly demonstrate that LKB1 is the major upstream kinase in skeletal muscle and that it is essential for maintaining mitochondrial marker proteins in skeletal muscle. These data provide evidence for a critical role of LKB1 in muscle physiology, one of which is maintaining basal levels of mitochondrial oxidative enzymes. Capacity for voluntary running is compromised with muscle and heart LKB1 deficiency. (+info)
Intra- and intermuscular variation in human quadriceps femoris architecture assessed in vivo.
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Despite the functional importance of the human quadriceps femoris in movements such as running, jumping, lifting and climbing, and the known effects of muscle architecture on muscle function, no research has fully described the complex architecture of this muscle group. We used ultrasound imaging techniques to measure muscle thickness, fascicle angle and fascicle length at multiple regions of the four quadriceps muscles in vivo in 31 recreationally active, but non-strength-trained adult men and women. Our analyses revealed a reasonable similarity in the superficial quadriceps muscles, which is suggestive of functional similarity (at least during the uni-joint knee extension task) given that they act via a common tendon. The deep vastus intermedius (VI) is architecturally dissimilar and therefore probably serves a different function(s). Architecture varies significantly along the length of the superficial muscles, which has implications for the accuracy of models that assume a constant intramuscular architecture. It might also have consequences for the efficiency of intra- and intermuscular force transmission. Our results provide some evidence that subjects with a given architecture of one superficial muscle, relative to the rest of the subject sample, also have a similar architecture in other superficial muscles. However, this is not necessarily true for vastus lateralis (VL), and was not the case for VI. Therefore, the relative architecture of one muscle cannot confidently be used to estimate the relative architecture of another. To confirm this, we calculated a value of whole quadriceps architecture by four different methods. Regardless of the method used, we found that the absolute or relative architecture of one muscle could not be used as an indicator of whole quadriceps architecture, although vastus medialis, possibly in concert with VL and the anterior portion of VI, could be used to provide a useful snapshot. Importantly, our estimates of whole quadriceps architecture show a gender difference in whole quadriceps muscle thickness, and that muscle thickness is positively correlated with fascicle angle whereas fascicle length is negatively, although weakly, correlated with fascicle angle. These results are supportive of the validity of estimates of whole quadriceps architecture. These data are interpreted with respect to their implications for neural control strategies, region-specific adaptations in muscle size in response to training, and gender-dependent differences in the response to exercise training. (+info)
A model for determining baseline morphometrics of the capillary bed in skeletal muscle.
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Changes in capillary diameter (CD) have been used to detect the effect of pharmacological interventions, physical treatments and ischaemic reperfusion injury in skin and muscle. For comparison, CDs within similar structures in the untreated limb of the same subject have been used as the control, with the assumption that CDs are the same in both limbs. This study employs light microscopic morphometry (LMM) to explore this premise, investigates the repeatability of LMM and determines the number of CDs that should be measured to produce a reliable result. Muscle biopsies were obtained from the left (L) and right (R) vastus lateralis of four rabbits and the left and right tibialis anterior of three vervet monkeys. Thin (1-micro m) resin sections were prepared for LMM examination and CDs were measured using computerised image analysis. To determine the repeatability of measurement, two specimens were re-measured on five occasions at monthly intervals. The mean CD of each biopsy from L and R limbs were compared and the number of measurements necessary to produce a result with less than a 3% difference was determined. A minimum of 58 and a maximum of 175 CDs were measured from each specimen. Repeated measurement of the same biopsies showed a non-significant mean difference of less than 2% in CD means between the first measurement and each of the four subsequent measurements. There was a non-significant difference of 3.7% in CD means between R and L limbs in one animal, in which less than 70 CDs were measured on each side. When 100 CDs or more were measured, the difference was always less than 2.3%. When grouped, the difference in CD means between L and R limbs was 0.5% in rabbits and 2.0% in vervet monkeys. The results confirm that firstly, CD data derived from a muscle in an untreated limb can be used as a control for experiment-mediated changes of CD in the other; secondly, LMM appears to be a reliable means of measuring CD; and thirdly, while fewer measurements may suffice, ideally 75-100 CDs are needed to provide a dependable result. (+info)
Effects of strength training on the incidence and progression of knee osteoarthritis.
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OBJECTIVE: Quadriceps weakness is a risk factor for incident knee osteoarthritis (OA). We describe a randomized controlled trial of effects of lower-extremity strength training on incidence and progression of knee OA. METHODS: A total of 221 older adults (mean age 69 years) were stratified by sex, presence of radiographic knee OA, and severity of knee pain, and were randomized to strength training (ST) or range-of-motion (ROM) exercises. Subjects exercised 3 times per week (twice at a fitness facility, once at home) for 12 weeks, followed by transition to home-based exercise after 12 months. Assessments of isokinetic lower-extremity strength and highly standardized knee radiographs were obtained at baseline and 30 months. RESULTS: Subjects in both groups lost lower-extremity strength over 30 months; however, the rate of loss was slower with ST than with ROM. Compared with ROM, ST decreased the mean rate of joint space narrowing (JSN) in osteoarthritic knees by 26% (P = not significant). However, the difference between ST and ROM groups with respect to frequency of knee OA progression in JSN consensus ratings was marginally significant (18% versus 28%; P = 0.094). In knees that were radiographically normal at baseline, JSN >0.50 mm was more common in ST than in ROM (34% versus 19%; P = 0.038). Incident JSN was unrelated to exercise adherence or changes in quadriceps strength or knee pain. CONCLUSION: The ST group retained more strength and exhibited less frequent progressive JSN over 30 months than the ROM group. The increase in incident JSN >0.50 mm in ST is unexplained and requires confirmation. (+info)