Fiber hypertrophy and increased oxidative capacity can occur simultaneously in pig glycolytic skeletal muscle

2014 ◽  
Vol 306 (4) ◽  
pp. C354-C363 ◽  
Author(s):  
T. L. Scheffler ◽  
J. M. Scheffler ◽  
S. Park ◽  
S. C. Kasten ◽  
Y. Wu ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Fiber ◽  
Citrate Synthase ◽  
Oxidative Capacity ◽  
Mitochondrial Proteins ◽  
Cross Sectional ◽  
Pig Muscle ◽  
Ryanodine Receptor 1 ◽  
Hydroxyacyl Coa Dehydrogenase ◽  
Amp Activated Protein Kinase

An inverse relationship between skeletal muscle fiber cross-sectional area (CSA) and oxidative capacity suggests that muscle fibers hypertrophy at the expense of oxidative capacity. Therefore, our objective was to utilize pigs possessing mutations associated with increased oxidative capacity [AMP-activated protein kinase (AMPKγ3R200Q)] or fiber hypertrophy [ryanodine receptor 1 (RyR1R615C)] to determine if these events occur in parallel. Longissimus muscle was collected from wild-type (control), AMPKγ3R200Q, RyR1R615C, and AMPKγ3R200Q-RyR1R615Cpigs. Regardless of AMPK genotype, RyRR615Cincreased fiber CSA by 35%. In contrast, AMPKγ3R200Qpig muscle exhibited greater citrate synthase and β-hydroxyacyl CoA dehydrogenase activity. Isolated mitochondria from AMPKγ3R200Qmuscle had greater maximal, ADP-stimulated oxygen consumption rate. Additionally, AMPKγ3R200Qmuscle contained more (∼50%) of the mitochondrial proteins succinate dehydrogenase and cytochrome c oxidase and more mitochondrial DNA. Surprisingly, RyR1R615Cincreased mitochondrial proteins and DNA, but this was not associated with improved oxidative capacity, suggesting that altered energy metabolism in RyR1R615Cmuscle influences mitochondrial proliferation and protein turnover. Thus pigs that possess both AMPKγ3R200Qand RyRR615Cexhibit increased muscle fiber CSA as well as greater oxidative capacity. Together, our findings support the notion that hypertrophy and enhanced oxidative capacity can occur simultaneously in skeletal muscle and suggest that the signaling mechanisms controlling these events are independently regulated.

scholarly journals Muscle Oxidative Capacity Is a Better Predictor of Insulin Sensitivity than Lipid Status

2003 ◽  
Vol 88 (11) ◽  
pp. 5444-5451 ◽  
Author(s):  
Clinton R. Bruce ◽  
Mitchell J. Anderson ◽  
Andrew L. Carey ◽  
David G. Newman ◽  
Arend Bonen ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Citrate Synthase ◽  
Oxidative Capacity ◽  
Fatty Acyl ◽  
Whole Body ◽  
Before And After ◽  
Hydroxyacyl Coa Dehydrogenase ◽  
Long Chain

Abstract We determined whole-body insulin sensitivity, long-chain fatty acyl coenzyme A (LCACoA) content, skeletal muscle triglyceride (TGm) concentration, fatty acid transporter protein content, and oxidative enzyme activity in eight patients with type 2 diabetes (TYPE 2); six healthy control subjects matched for age (OLD), body mass index, percentage of body fat, and maximum pulmonary O2 uptake; nine well-trained athletes (TRAINED); and four age-matched controls (YOUNG). Muscle biopsies from the vastus lateralis were taken before and after a 2-h euglycemic-hyperinsulinemic clamp. Oxidative enzyme activities, fatty acid transporters (FAT/CD36 and FABPpm), and TGm were measured from basal muscle samples, and total LCACoA content was determined before and after insulin stimulation. Whole-body insulin-stimulated glucose uptake was lower in TYPE 2 (P < 0.05) than in OLD, YOUNG, and TRAINED. TGm was elevated in TYPE 2 compared with all other groups (P < 0.05). However, both basal and insulin-stimulated skeletal muscle LCACoA content were similar. Basal citrate synthase activity was higher in TRAINED (P < 0.01), whereas β-hydroxyacyl CoA dehydrogenase activity was higher in TRAINED compared with TYPE 2 and OLD. There was a significant relationship between the oxidative capacity of skeletal muscle and insulin sensitivity (citrate synthase, r = 0.71, P < 0.001; β-hydroxyacyl CoA dehydrogenase, r = 0.61, P = 0.001). No differences were found in FAT/CD36 protein content between groups. In contrast, FABPpm protein was lower in OLD compared with TYPE 2 and YOUNG (P < 0.05). In conclusion, despite markedly elevated skeletal muscle TGm in type 2 diabetic patients and strikingly different levels of whole-body glucose disposal, both basal and insulin-stimulated LCACoA content were similar across groups. Furthermore, skeletal muscle oxidative capacity was a better predictor of insulin sensitivity than either TGm concentration or long-chain fatty acyl CoA content.

scholarly journals Fiber Composition and Oxidative Capacity of Hamster Skeletal Muscle

2002 ◽  
Vol 50 (12) ◽  
pp. 1685-1692 ◽  
Author(s):  
John P. Mattson ◽  
Todd A. Miller ◽  
David C. Poole ◽  
Michael D. Delp
Keyword(s):  
Skeletal Muscle ◽  
Citrate Synthase ◽  
Fiber Type ◽  
Rank Order ◽  
Oxidative Capacity ◽  
Type I ◽  
Cross Sectional ◽  
Physiological Investigation ◽  
Combining Data ◽  
Type I Fibers

The hamster is a valuable biological model for physiological investigation. Despite the obvious importance of the integration of cardiorespiratory and muscular system function, little information is available regarding hamster muscle fiber type and oxidative capacity, both of which are key determinants of muscle function. The purpose of this investigation was to measure immunohistochemically the relative composition and size of muscle fibers composed of types I, IIA, IIX, and IIB fibers in hamster skeletal muscle. The oxidative capacity of each muscle was also assessed by measuring citrate synthase activity. Twenty-eight hindlimb, respiratory, and facial muscles or muscle parts from adult (144–147 g bw) male Syrian golden hamsters ( n=3) were dissected bilaterally, weighed, and frozen for immunohistochemical and biochemical analysis. Combining data from all 28 muscles analyzed, type I fibers made up 5% of the muscle mass, type IIA fibers 16%, type IIX fibers 39%, and type IIB fibers 40%. Mean fiber cross-sectional area across muscles was 1665 ± 328 μm2 for type I fibers, 1900 ± 417 μm2 for type IIA fibers, 3230 ± 784 μm2 for type IIX fibers, and 4171 ± 864 μm2 for type IIB fibers. Citrate synthase activity was most closely related to the population of type IIA fibers ( r=0.68, p<0.0001) and was in the rank order of type IIA > I > IIX > IIB. These data demonstrate that hamster skeletal muscle is predominantly composed of type IIB and IIX fibers.

scholarly journals Impaired exercise training-induced muscle fiber hypertrophy and Akt/mTOR pathway activation in hypoxemic patients with COPD

2015 ◽  
Vol 118 (8) ◽  
pp. 1040-1049 ◽  
Author(s):  
Frédéric Costes ◽  
Harry Gosker ◽  
Léonard Feasson ◽  
Marine Desgeorges ◽  
Marco Kelders ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Muscle Fiber ◽  
Citrate Synthase ◽  
Vastus Lateralis ◽  
C2c12 Myotubes ◽  
Chronic Obstructive ◽  
Vastus Lateralis Muscle ◽  
Cross Sectional ◽  
Gsk 3Β

Exercise training (ExTr) is largely used to improve functional capacity in patients with chronic obstructive pulmonary disease (COPD). However, ExTr only partially restores muscle function in patients with COPD, suggesting that confounding factors may limit the efficiency of ExTr. In the present study, we hypothesized that skeletal muscle adaptations triggered by ExTr could be compromised in hypoxemic patients with COPD. Vastus lateralis muscle biopsies were obtained from patients with COPD who were either normoxemic ( n = 15, resting arterial Po2 = 68.5 ± 1.5 mmHg) or hypoxemic ( n = 8, resting arterial Po2 = 57.0 ± 1.0 mmHg) before and after a 2-mo ExTr program. ExTr induced a significant increase in exercise capacity both in normoxemic and hypoxemic patients with COPD. However, ExTr increased citrate synthase and lactate dehydrogenase enzyme activities only in skeletal muscle of normoxemic patients. Similarly, muscle fiber cross-sectional area and capillary-to-fiber ratio were increased only in patients who were normoxemic. Expression of atrogenes (MuRF1, MAFbx/Atrogin-1) and autophagy-related genes (Beclin, LC3, Bnip, Gabarapl) remained unchanged in both groups. Phosphorylation of Akt (Ser473), GSK-3β (Ser9), and p70S6k (Thr389) was nonsignificantly increased in normoxemic patients in response to ExTr, but it was significantly decreased in hypoxemic patients. We further showed on C2C12 myotubes that hypoxia completely prevented insulin-like growth factor-1-induced phosphorylation of Akt, GSK-3β, and p70S6K. Together, our observations suggest a role for hypoxemia in the adaptive response of skeletal muscle of patients with COPD in an ExTr program.

scholarly journals Skeletal muscle adaptations to microgravity exposure in the mouse

2003 ◽  
Vol 95 (6) ◽  
pp. 2462-2470 ◽  
Author(s):  
B. C. Harrison ◽  
D. L. Allen ◽  
B. Girten ◽  
L. S. Stodieck ◽  
P. J. Kostenuik ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Fiber ◽  
Citrate Synthase ◽  
Space Shuttle ◽  
Immunohistochemical Analysis ◽  
Cross Sectional Area ◽  
Fiber Types ◽  
Sectional Area ◽  
Cross Sectional ◽  
Isoform Expression

To investigate the effects of microgravity on murine skeletal muscle fiber size, muscle contractile protein, and enzymatic activity, female C57BL/6J mice, aged 64 days, were divided into animal enclosure module (AEM) ground control and spaceflight (SF) treatment groups. SF animals were flown on the space shuttle Endeavour (STS-108/UF-1) and subjected to ∼11 days and 19 h of microgravity. Immunohistochemical analysis of muscle fiber cross-sectional area revealed that, in each of the muscles analyzed, mean muscle fiber cross-sectional area was significantly reduced ( P < 0.0001) for all fiber types for SF vs. AEM control. In the soleus, immunohistochemical analysis of myosin heavy chain (MHC) isoform expression revealed a significant increase in the percentage of muscle fibers expressing MHC IIx and MHC IIb ( P < 0.05). For the gastrocnemius and plantaris, no significant changes in MHC isoform expression were observed. For the muscles analyzed, no alterations in MHC I or MHC IIa protein expression were observed. Enzymatic analysis of the gastrocnemius revealed a significant decrease in citrate synthase activity in SF vs. AEM control.

HIF-1α in endurance training: suppression of oxidative metabolism

2007 ◽  
Vol 293 (5) ◽  
pp. R2059-R2069 ◽  
Author(s):  
Steven D. Mason ◽  
Helene Rundqvist ◽  
Ioanna Papandreou ◽  
Roger Duh ◽  
Wayne J. McNulty ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Endurance Training ◽  
Oxidative Metabolism ◽  
Hypoxia Inducible Factor ◽  
Transcriptional Response ◽  
Oxidative Capacity ◽  
Pyruvate Dehydrogenase Kinase ◽  
Amp Activated Protein Kinase ◽  
Training Protocol

During endurance training, exercising skeletal muscle experiences severe and repetitive oxygen stress. The primary transcriptional response factor for acclimation to hypoxic stress is hypoxia-inducible factor-1α (HIF-1α), which upregulates glycolysis and angiogenesis in response to low levels of tissue oxygenation. To examine the role of HIF-1α in endurance training, we have created mice specifically lacking skeletal muscle HIF-1α and subjected them to an endurance training protocol. We found that only wild-type mice improve their oxidative capacity, as measured by the respiratory exchange ratio; surprisingly, we found that HIF-1α null mice have already upregulated this parameter without training. Furthermore, untrained HIF-1α null mice have an increased capillary to fiber ratio and elevated oxidative enzyme activities. These changes correlate with constitutively activated AMP-activated protein kinase in the HIF-1α null muscles. Additionally, HIF-1α null muscles have decreased expression of pyruvate dehydrogenase kinase I, a HIF-1α target that inhibits oxidative metabolism. These data demonstrate that removal of HIF-1α causes an adaptive response in skeletal muscle akin to endurance training and provides evidence for the suppression of mitochondrial biogenesis by HIF-1α in normal tissue.

Skeletal muscle biochemical adaptations to exercise training in miniature swine

1997 ◽  
Vol 82 (6) ◽  
pp. 1862-1868 ◽  
Author(s):  
Richard M. McAllister ◽  
Brian L. Reiter ◽  
John F. Amann ◽  
M. Harold Laughlin
Keyword(s):  
Skeletal Muscle ◽  
Antioxidant Enzymes ◽  
Lactate Dehydrogenase ◽  
Exercise Training ◽  
Endurance Exercise ◽  
Oxidative Capacity ◽  
Treadmill Running ◽  
Miniature Swine ◽  
Endurance Exercise Training ◽  
Hydroxyacyl Coa Dehydrogenase

McAllister, Richard M., Brian L. Reiter, John F. Amann, and M. Harold Laughlin. Skeletal muscle biochemical adaptations to exercise training in miniature swine. J. Appl. Physiol. 82(6): 1862–1868, 1997.—The primary purpose of this study was to test the hypothesis that endurance exercise training induces increased oxidative capacity in porcine skeletal muscle. To test this hypothesis, female miniature swine were either trained by treadmill running 5 days/wk over 16–20 wk (Trn; n = 35) or pen confined (Sed; n = 33). Myocardial hypertrophy, lower heart rates during submaximal stages of a maximal treadmill running test, and increased running time to exhaustion during that test were indicative of training efficacy. A variety of skeletal muscles were sampled and subsequently assayed for the enzymes citrate synthase (CS), 3-hydroxyacyl-CoA dehydrogenase, and lactate dehydrogenase and for antioxidant enzymes. Fiber type composition of a representative muscle was also determined histochemically. The largest increase in CS activity (62%) was found in the gluteus maximus muscle (Sed, 14.7 ± 1.1 μmol ⋅ min−1 ⋅ g−1; Trn, 23.9 ± 1.0; P < 0.0005). Muscles exhibiting increased CS activity, however, were located primarily in the forelimb; ankle and knee extensor and respiratory muscles were unchanged with training. Only two muscles exhibited higher 3-hydroxyacyl-CoA dehydrogenase activity in Trn compared with Sed. Lactate dehydrogenase activity was unchanged with training, as were activities of antioxidant enzymes. Histochemical analysis of the triceps brachii muscle (long head) revealed lower type IIB fiber numbers in Trn (Sed, 42 ± 6%; Trn, 10 ± 4; P < 0.01) and greater type IID/X fiber numbers (Sed, 11 ± 2; Trn, 22 ± 3; P < 0.025). These findings indicate that porcine skeletal muscle adapts to endurance exercise training in a manner similar to muscle of humans and other animal models, with increased oxidative capacity. Specific muscles exhibiting these adaptations, however, differ between the miniature swine and other species.

Blood flow to different skeletal muscle fiber types during contraction

1983 ◽  
Vol 245 (2) ◽  
pp. H265-H275 ◽  
Author(s):  
B. G. Mackie ◽  
R. L. Terjung
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Muscle Fiber ◽  
Fiber Type ◽  
Oxidative Capacity ◽  
Skeletal Muscle Fiber ◽  
Muscle Fiber Types ◽  
Fiber Types ◽  
Blood Flows ◽  
Fast Twitch

Blood flow to fast-twitch red (FTR), fast-twitch white (FTW), and slow-twitch red (STR) muscle fiber sections of the gastrocnemius-plantaris-soleus muscle group was determined using 15 +/- 3-microns microspheres during in situ stimulation in pentobarbital-anesthetized rats. Steady-state blood flows were assessed during the 10th min of contraction using twitch (0.1, 0.5, 1, 3, and 5 Hz) and tetanic (7.5, 15, 30, 60, and 120/min) stimulation conditions. In addition, an earlier blood flow determination was begun at 3 min (twitch series) or at 30 s (tetanic series) of stimulation. Blood flow was highest in the FTR (220-240 ml X min-1 X 100 g-1), intermediate in the STR (140), and lowest in the FTW (70-80) section during tetanic contraction conditions estimated to coincide with the peak aerobic function of each fiber type. These blood flows are fairly proportional to the differences in oxidative capacity among fiber types. Further, their absolute values are similar to those predicted from the relationship between blood flow and oxidative capacity found by others for dog and cat muscles. During low-frequency contraction conditions, initial blood flow to the FTR and STR sections were excessively high and not dependent on contraction frequency. However, blood flows subsequently decreased to values in keeping with the relative energy demands. In contrast, FTW muscle did not exhibit this time-dependent relative hyperemia. Thus, besides the obvious quantitative differences between skeletal muscle fiber types, there are qualitative differences in blood flow response during contractions. Our findings establish that, based on fiber type composition, a heterogeneity in blood flow distribution can occur within a whole muscle during contraction.

Influence of training on skeletal muscle enzymatic adaptations in normal and diabetic rats

1985 ◽  
Vol 249 (4) ◽  
pp. E360-E365 ◽  
Author(s):  
E. G. Noble ◽  
C. D. Ianuzzo
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Citrate Synthase ◽  
Diabetic Rats ◽  
Muscle Fiber Types ◽  
Fiber Types ◽  
Marker Enzymes ◽  
Oxidative Potential ◽  
Hydroxyacyl Coa Dehydrogenase ◽  
Fast Twitch

Muscle homogenates representing slow-twitch oxidative, fast-twitch oxidative-glycolytic, fast-twitch glycolytic, and mixed fiber types were prepared from normal, diabetic, and insulin-treated diabetic rats. Diabetes was induced by injection of 80 mg . kg-1 of streptozotocin. The activities of citrate synthase, succinate dehydrogenase, and 3-hydroxyacyl-CoA dehydrogenase were employed as markers of oxidative potential, whereas phosphorylase, hexokinase, and phosphofructokinase activities were used as an indication of glycolytic capacity. Diabetes was associated with a general decrement in the activity of oxidative marker enzymes for all fiber types except the fast-twitch glycolytic fiber. In contrast, the fast-twitch glycolytic fibers demonstrated the greatest decline in glycolytic enzymatic activity. Insulin-treated animals, either trained or untrained, exhibited enzyme activities similar to their normal counterparts. Exercise training of diabetic rats mimicked the effect of insulin treatment and caused a near normalization of the activity of the marker enzymes. These findings suggest that the enzymatic potential of all skeletal muscle fiber types of diabetic rats may be normalized by exercise training even in the absence of significant amounts of insulin.

scholarly journals Combined Training Enhances Skeletal Muscle Mitochondrial Oxidative Capacity Independent of Age

2015 ◽  
Vol 100 (4) ◽  
pp. 1654-1663 ◽  
Author(s):  
Brian A. Irving ◽  
Ian R. Lanza ◽  
Gregory C. Henderson ◽  
Rajesh R. Rao ◽  
Bruce M. Spiegelman ◽  
...  
Keyword(s):  
Older Adults ◽  
Skeletal Muscle ◽  
Body Composition ◽  
Transcription Factors ◽  
Muscle Strength ◽  
Oxidative Capacity ◽  
Physical Characteristics ◽  
Mitochondrial Proteins ◽  
Combined Training ◽  
Skeletal Muscle Strength

Context: Skeletal muscle from sedentary older adults exhibits reduced mitochondrial abundance and oxidative capacity. Objective: The primary objective was to determine whether 8 weeks of combined training (CT) has a more robust effect than endurance training (ET) or resistance training (RT) on mitochondrial physiology in healthy young (18–30 years) and older (≥65 years) adults. Intervention: Thirty-four young and 31 older adults were randomly assigned to 8 weeks of ET, RT, and control/CT. Control subjects completed 8 weeks of no exercise (control) followed by 8 weeks of CT. Body composition, skeletal muscle strength, and peak oxygen uptake were measured before and after the intervention. Vastus lateralis muscle biopsy samples were obtained before and 48 hours after the intervention. Mitochondrial physiology was evaluated by high-resolution respirometry and expression of mitochondrial proteins and transcription factors by quantitative PCR and immunoblotting. Results: ET and CT significantly increased oxidative capacity and expression of mitochondrial proteins and transcription factors. All training modalities improved body composition, cardiorespiratory fitness, and skeletal muscle strength. CT induced the most robust improvements in mitochondria-related outcomes and physical characteristics despite lower training volumes for the ET and RT components. Importantly, most of the adaptations to training occurred independent of age. Conclusion: Collectively, these results demonstrate that both ET and CT increase muscle mitochondrial abundance and capacity although CT induced the most robust improvements in the outcomes measured. In conclusion, CT provides a robust exercise regimen to improve muscle mitochondrial outcomes and physical characteristics independent of age.

scholarly journals Exposure to cigarette smoke induces overexpression of von Hippel-Lindau tumor suppressor in mouse skeletal muscle

2012 ◽  
Vol 303 (6) ◽  
pp. L519-L527 ◽  
Author(s):  
Vladimir T. Basic ◽  
Elsa Tadele ◽  
Ali Ateia Elmabsout ◽  
Hongwei Yao ◽  
Irfan Rahman ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Tumor Suppressor ◽  
Cigarette Smoke ◽  
Muscle Fiber ◽  
Exercise Tolerance ◽  
Skeletal Muscles ◽  
Cross Sectional Area ◽  
Sectional Area ◽  
Cross Sectional ◽  
Von Hippel Lindau

Cigarette smoke (CS) is a well-established risk factor in the development of chronic obstructive pulmonary disease (COPD). In contrast, the extent to which CS exposure contributes to the development of the systemic manifestations of COPD, such as skeletal muscle dysfunction and wasting, remains largely unknown. Decreased skeletal muscle capillarization has been previously reported in early stages of COPD and might play an important role in the development of COPD-associated skeletal muscle abnormalities. To investigate the effects of chronic CS exposure on skeletal muscle capillarization and exercise tolerance, a mouse model of CS exposure was used. The 129/SvJ mice were exposed to CS for 6 mo, and the expression of putative elements of the hypoxia-angiogenic signaling cascade as well as muscle capillarization were studied. Additionally, functional tests assessing exercise tolerance/endurance were performed in mice. Compared with controls, skeletal muscles from CS-exposed mice exhibited significantly enhanced expression of von Hippel-Lindau tumor suppressor (VHL), ubiquitin-conjugating enzyme E2D1 (UBE2D1), and prolyl hydroxylase-2 (PHD2). In contrast, hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) expression was reduced. Furthermore, reduced muscle fiber cross-sectional area, decreased skeletal muscle capillarization, and reduced exercise tolerance were also observed in CS-exposed animals. Taken together, the current results provide evidence linking chronic CS exposure and induction of VHL expression in skeletal muscles leading toward impaired hypoxia-angiogenesis signal transduction, reduced muscle fiber cross-sectional area, and decreased exercise tolerance.

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