Effect of acute exercise and exercise training on VEGF splice variants in human skeletal muscle

2004 ◽  
Vol 287 (2) ◽  
pp. R397-R402 ◽  
Author(s):  
Lotte Jensen ◽  
Henriette Pilegaard ◽  
P. Darrell Neufer ◽  
Ylva Hellsten
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Human Skeletal Muscle ◽  
Acute Exercise ◽  
Splice Variants ◽  
Knee Extensor ◽  
Vastus Lateralis Muscle ◽  
Mrna Levels ◽  
Vegf Mrna ◽  
Exercise Induced

The present study investigated the effect of an acute exercise bout on the mRNA response of vascular endothelial growth factor (VEGF) splice variants in untrained and trained human skeletal muscle. Seven habitually active young men performed one-legged knee-extensor exercise training at an intensity corresponding to ∼70% of the maximal workload in an incremental test five times/week for 4 wk. Biopsies were obtained from the vastus lateralis muscle of the trained and untrained leg 40 h after the last training session. The subjects then performed 3 h of two-legged knee-extensor exercise, and biopsies were obtained from both legs after 0, 2, 6, and 24 h of recovery. Real-time PCR was used to examine the expression of VEGF mRNA containing exon 1 and 2 (all VEGF isoforms), exon 6 or exon 7, and VEGF165mRNA. Acute exercise induced an increase ( P < 0.05) in total VEGF mRNA levels as well as VEGF165and VEGF splice variants containing exon 7 at 0, 2, and 6 h of recovery. The increase in VEGF mRNA was higher in the untrained than in the trained leg ( P < 0.05). The results suggest that in human skeletal muscle, acute exercise increases total VEGF mRNA, an increase that appears to be explained mainly by an increase in VEGF165mRNA. Furthermore, 4 wk of training attenuated the exercise-induced response in skeletal muscle VEGF165mRNA.

Exercise adaptation attenuates VEGF gene expression in human skeletal muscle

2000 ◽  
Vol 279 (2) ◽  
pp. H772-H778 ◽  
Author(s):  
R. S. Richardson ◽  
H. Wagner ◽  
S. R. D. Mudaliar ◽  
E. Saucedo ◽  
R. Henry ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Human Skeletal Muscle ◽  
Acute Exercise ◽  
Vastus Lateralis ◽  
Northern Analysis ◽  
Endothelial Cell Proliferation ◽  
Vastus Lateralis Muscle ◽  
Mrna Levels ◽  
Exercise Adaptation

Angiogenesis is a component of the multifactoral adaptation to exercise training, and vascular endothelial growth factor (VEGF) is involved in extracellular matrix changes and endothelial cell proliferation. However, there is limited evidence supporting the role of VEGF in the exercise training response. Thus we studied mRNA levels of VEGF, using quantitative Northern analysis, in untrained and trained human skeletal muscle at rest and after a single bout of exercise. Single leg knee-extension provided the acute exercise stimulus and the training modality. Four biopsies were collected from the vastus lateralis muscle at rest in the untrained and trained conditions before and after exercise. Training resulted in a 35% increase in muscle oxygen consumption and an 18% increase in number of capillaries per muscle fiber. At rest, VEGF/18S mRNA levels were similar before (0.38 ± 0.04) and after (1.2 ± 0.4) training. When muscle was untrained, acute exercise greatly elevated VEGF/18S mRNA levels (16.9 ± 6.7). The VEGF/18S mRNA response to acute exercise in the trained state was markedly attenuated (5.4 ± 1.3). These data support the concept that VEGF is involved in exercise-induced skeletal muscle angiogenesis and appears to be subject to a negative feedback mechanism as exercise adaptations occur.

Human VEGF gene expression in skeletal muscle: effect of acute normoxic and hypoxic exercise

1999 ◽  
Vol 277 (6) ◽  
pp. H2247-H2252 ◽  
Author(s):  
R. S. Richardson ◽  
H. Wagner ◽  
S. R. D. Mudaliar ◽  
R. Henry ◽  
E. A. Noyszewski ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Growth Factor ◽  
Acute Exercise ◽  
Work Rate ◽  
Northern Analysis ◽  
Endothelial Cell Proliferation ◽  
Vastus Lateralis Muscle ◽  
Mrna Levels ◽  
Vegf Mrna ◽  
Exercise Induced

Vascular endothelial growth factor (VEGF) is involved in extracellular matrix changes and endothelial cell proliferation, both of which are precursors to new capillary growth. Angiogenesis is a vital adaptation to exercise training, and the exercise-induced reduction in intracellular[Formula: see text] has been proposed as a stimulus for this process. Thus we studied muscle cell[Formula: see text] [myoglobin[Formula: see text]([Formula: see text])] during exercise in normoxia and in hypoxia (12% O2) and studied the mRNA levels of VEGF in six untrained subjects after a single bout of exercise by quantitative Northern analysis. Single-leg knee extension provided the acute exercise stimulus: a maximal test followed by 30 min at 50% of the peak work rate achieved in this graded test. Because peak work rate was not affected by hypoxia, the absolute and relative work rates were identical in hypoxia and normoxia. Three pericutaneous needle biopsies were collected from the vastus lateralis muscle, one at rest and then the others at 1 h after exercise in normoxia or hypoxia. At rest (control), VEGF mRNA levels were very low (0.38 ± 0.04 VEGF/18S). After exercise in normoxia or hypoxia, VEGF mRNA levels were much greater (16.9 ± 6.7 or 7.1 ± 1.8 VEGF/18S, respectively). In contrast, there was no measurable basic fibroblast growth factor mRNA response to exercise at this 1-h postexercise time point. Magnetic resonance spectroscopy of myoglobin confirmed a reduction in[Formula: see text] in hypoxia (3.8 ± 0.3 mmHg) compared with normoxia (7.2 ± 0.6 mmHg) but failed to reveal a relationship between [Formula: see text] during exercise and VEGF expression. This VEGF mRNA increase in response to acute exercise supports the concept that VEGF is involved in exercise-induced skeletal muscle angiogenesis but questions the importance of a reduced cellular [Formula: see text]as a stimulus for this response.

Transcriptional regulation of gene expression in human skeletal muscle during recovery from exercise

2000 ◽  
Vol 279 (4) ◽  
pp. E806-E814 ◽  
Author(s):  
Henriette Pilegaard ◽  
George A. Ordway ◽  
Bengt Saltin ◽  
P. Darrell Neufer
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Human Skeletal Muscle ◽  
Molecular Mechanisms ◽  
Uncoupling Protein ◽  
Pyruvate Dehydrogenase Kinase ◽  
Heme Oxygenase 1 ◽  
Metabolic Efficiency ◽  
Vastus Lateralis Muscle ◽  
Mrna Levels

Exercise training elicits a number of adaptive changes in skeletal muscle that result in an improved metabolic efficiency. The molecular mechanisms mediating the cellular adaptations to exercise training in human skeletal muscle are unknown. To test the hypothesis that recovery from exercise is associated with transcriptional activation of specific genes, six untrained male subjects completed 60–90 min of exhaustive one-legged knee extensor exercise for five consecutive days. On day 5, nuclei were isolated from biopsies of the vastus lateralis muscle of the untrained and the trained leg before exercise and from the trained leg immediately after exercise and after 15 min, 1 h, 2 h, and 4 h of recovery. Transcriptional activity of the uncoupling protein 3 (UCP3), pyruvate dehydrogenase kinase 4 (PDK4), and heme oxygenase-1 (HO-1) genes (relative to β-actin) increased by three- to sevenfold in response to exercise, peaking after 1–2 h of recovery. Increases in mRNA levels followed changes in transcription, peaking between 2 and 4 h after exercise. Lipoprotein lipase and carnitine pamitoyltransferase I gene transcription and mRNA levels showed similar but less dramatic induction patterns, with increases ranging from two- to threefold. In a separate study, a single 4-h bout of cycling exercise ( n = 4) elicited from 5 to >20-fold increases in UCP3, PDK4, and HO-1 transcription, suggesting that activation of these genes may be related to the duration or intensity of exercise. These data demonstrate that exercise induces transient increases in transcription of metabolic genes in human skeletal muscle. Moreover, the findings suggest that the cumulative effects of transient increases in transcription during recovery from consecutive bouts of exercise may represent the underlying kinetic basis for the cellular adaptations associated with exercise training.

scholarly journals Endurance training reduces the contraction-induced interleukin-6 mRNA expression in human skeletal muscle

2004 ◽  
Vol 287 (6) ◽  
pp. E1189-E1194 ◽  
Author(s):  
Christian P. Fischer ◽  
Peter Plomgaard ◽  
Anne K. Hansen ◽  
Henriette Pilegaard ◽  
Bengt Saltin ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Mrna Expression ◽  
Muscle Glycogen ◽  
Human Skeletal Muscle ◽  
Acute Exercise ◽  
Glycogen Content ◽  
Knee Extensor ◽  
Exercise Induced ◽  
Response To Exercise ◽  
Resting Muscle

Contracting skeletal muscle expresses large amounts of IL-6. Because 1) IL-6 mRNA expression in contracting skeletal muscle is enhanced by low muscle glycogen content, and 2) IL-6 increases lipolysis and oxidation of fatty acids, we hypothesized that regular exercise training, associated with increased levels of resting muscle glycogen and enhanced capacity to oxidize fatty acids, would lead to a less-pronounced increase of skeletal muscle IL-6 mRNA in response to acute exercise. Thus, before and after 10 wk of knee extensor endurance training, skeletal muscle IL-6 mRNA expression was determined in young healthy men ( n = 7) in response to 3 h of dynamic knee extensor exercise, using the same relative workload. Maximal power output, time to exhaustion during submaximal exercise, resting muscle glycogen content, and citrate synthase and 3-hydroxyacyl-CoA dehydrogenase enzyme activity were all significantly enhanced by training. IL-6 mRNA expression in resting skeletal muscle did not change in response to training. However, although absolute workload during acute exercise was 44% higher ( P < 0.05) after the training period, skeletal muscle IL-6 mRNA content increased 76-fold ( P < 0.05) in response to exercise before the training period, but only 8-fold ( P < 0.05, relative to rest and pretraining) in response to exercise after training. Furthermore, the exercise-induced increase of plasma IL-6 ( P < 0.05, pre- and posttraining) was not higher after training despite higher absolute work intensity. In conclusion, the magnitude of the exercise-induced IL-6 mRNA expression in contracting human skeletal muscle was markedly reduced by 10 wk of training.

Skeletal muscle adaptations to exercise are not influenced by metformin treatment in humans: secondary analyses of two randomised, clinical trials.

2021 ◽  
Author(s):  
Nanna Skytt Pilmark ◽  
Laura Oberholzer ◽  
Jens Frey Halling ◽  
Jonas M. Kristensen ◽  
Christina Pedersen Bønding ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Exercise Training ◽  
Human Skeletal Muscle ◽  
Acute Exercise ◽  
Metformin Treatment ◽  
Ampk Activation ◽  
Double Blind ◽  
Parallel Group ◽  
Exercise Induced

Metformin and exercise both improve glycemic control, but in vitro studies have indicated that an interaction between metformin and exercise occurs in skeletal muscle, suggesting a blunting effect of metformin on exercise training adaptations. Two studies (a double-blind, parallel-group, randomized clinical trial conducted in 29 glucose-intolerant individuals and a double-blind, cross-over trial conducted in 15 healthy lean males) were included in this paper. In both studies, the effect of acute exercise +/- metformin treatment on different skeletal muscle variables, previously suggested to be involved in a pharmaco-physiological interaction between metformin and exercise, was assessed. Furthermore, in the parallel-group trial, the effect of 12 weeks of exercise training was assessed. Skeletal muscle biopsies were obtained before and after acute exercise and 12 weeks of exercise training, and mitochondrial respiration, oxidative stress and AMPK activation was determined. Metformin did not significantly affect the effects of acute exercise or exercise training on mitochondrial respiration, oxidative stress or AMPK activation, indicating that the response to acute exercise and exercise training adaptations in skeletal muscle is not affected by metformin treatment. Further studies are needed to investigate whether an interaction between metformin and exercise is present in other tissues, e.g. the gut. Trial registration: ClinicalTrials.gov (NCT03316690 and NCT02951260). Novelty bullets • Metformin does not affect exercise-induced alterations in mitochondrial respiratory capacity in human skeletal muscle • Metformin does not affect exercise-induced alterations in systemic levels of oxidative stress nor emission of reactive oxygen species from human skeletal muscle • Metformin does not affect exercise-induced AMPK activation in human skeletal muscle

PGC-1α mediates exercise-induced skeletal muscle VEGF expression in mice

2009 ◽  
Vol 297 (1) ◽  
pp. E92-E103 ◽  
Author(s):  
Lotte Leick ◽  
Ylva Hellsten ◽  
Joachim Fentz ◽  
Stine S. Lyngby ◽  
Jørgen F. P. Wojtaszewski ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Protein Expression ◽  
Protein Content ◽  
Acute Exercise ◽  
Whole Body ◽  
Vegf Expression ◽  
Vegf Mrna ◽  
Exercise Induced ◽  
Vegf Protein

The aim of the present study was to test the hypothesis that PGC-1α is required for exercise-induced VEGF expression in both young and old mice and that AMPK activation leads to increased VEGF expression through a PGC-1α-dependent mechanism. Whole body PGC-1α knockout (KO) and littermate wild-type (WT) mice were submitted to either 1) 5 wk of exercise training, 2) lifelong (from 2 to 13 mo of age) exercise training in activity wheel, 3) a single exercise bout, or 4) 4 wk of daily subcutaneous AICAR or saline injections. In skeletal muscle of PGC-1α KO mice, VEGF protein expression was ∼60–80% lower and the capillary-to-fiber ratio ∼20% lower than in WT. Basal VEGF mRNA expression was similar in WT and PGC-1α KO mice, but acute exercise and AICAR treatment increased the VEGF mRNA content in WT mice only. Exercise training of young mice increased skeletal muscle VEGF protein expression ∼50% in WT mice but with no effect in PGC-1α KO mice. Furthermore, a training-induced prevention of an age-associated decline in VEGF protein content was observed in WT but not in PGC-1α KO muscles. In addition, repeated AICAR treatments increased skeletal muscle VEGF protein expression ∼15% in WT but not in PGC-1α KO mice. This study shows that PGC-1α is essential for exercise-induced upregulation of skeletal muscle VEGF expression and for a training-induced prevention of an age-associated decline in VEGF protein content. Furthermore, the findings suggest an AMPK-mediated regulation of VEGF expression through PGC-1α.

Muscle microvascular adaptation and angiogenic gene induction in response to exercise training are attenuated in middle-aged rats

2015 ◽  
Vol 11 (1) ◽  
pp. 23-33
Author(s):  
J. Suzuki
Keyword(s):  
Exercise Training ◽  
Acute Exercise ◽  
Young Group ◽  
Treadmill Running ◽  
Mrna Levels ◽  
Aged Rats ◽  
Middle Aged ◽  
Vegf Mrna ◽  
Aged Group ◽  
Exercise Induced

This study was designed to investigate exercise-induced changes in muscle capillarisation, the mRNA expression of angiogenic genes, and microRNA levels in young and middle-aged rats. Rats in the training groups were subjected to treadmill running 5 days a week for 3 weeks. The exercise protocol for the young (12-week old) group was 20-25 m/min, 40-60 min/day with a gradient of 15%, and for the middle-aged (12-month old) group was 18-20 m/min, 40-60 min/day with a gradient of 5%. The enzyme histochemical identification of capillary profiles was performed on cross-sections of gastrocnemius muscle. Total RNA was isolated, reverse transcription was performed, and mRNA and microRNA levels were determined by real-time PCR. The capillary-to-fibre ratio was significantly increased by exercise training in the young group (by 10%), but only slightly in the middle-aged (by 5%) group. Vascular endothecial growth factor (VEGF) mRNA levels were at significantly higher values after acute exercise (1.6-fold) and the 3-week training protocol (1.9-fold) in the young group, but not in the middle-aged group. VEGF protein expression levels were significantly increased after training in the young group only. Endothelial nitric oxide synthase, VEGF-R2 and thrombospondin-1 mRNA levels were significantly lower in the middle-aged group than in the young group. Anti-angiogenic miR-195 levels were significantly enhanced by exercise training in the middle-aged group only. These results indicated that the exercise-induced adaptation of muscle capillarity was attenuated in middle-aged rats, possibly by the lower induction of VEGF and up-regulation of anti-angiogenic miRNA expression.

Effect of birth weight and 12 weeks of exercise training on exercise-induced AMPK signaling in human skeletal muscle

2013 ◽  
Vol 304 (12) ◽  
pp. E1379-E1390 ◽  
Author(s):  
Brynjulf Mortensen ◽  
Janne R. Hingst ◽  
Nicklas Frederiksen ◽  
Rikke W. W. Hansen ◽  
Caroline S. Christiansen ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Birth Weight ◽  
Exercise Training ◽  
Acute Exercise ◽  
Mrna Levels ◽  
Ampk Activation ◽  
Ampk Signaling ◽  
Protein Levels ◽  
Before And After ◽  
Exercise Induced

Subjects with a low birth weight (LBW) display increased risk of developing type 2 diabetes (T2D). We hypothesized that this is associated with defects in muscle adaptations following acute and regular physical activity, evident by impairments in the exercise-induced activation of AMPK signaling. We investigated 21 LBW and 21 normal birth weight (NBW) subjects during 1 h of acute exercise performed at the same relative workload before and after 12 wk of exercise training. Multiple skeletal muscle biopsies were obtained before and after exercise. Protein levels and phosphorylation status were determined by Western blotting. AMPK activities were measured using activity assays. Protein levels of AMPKα1 and -γ1 were significantly increased, whereas AMPKγ3 levels decreased with training independently of group. The LBW group had higher exercise-induced AMPK Thr172 phosphorylation before training and higher exercise-induced ACC2 Ser221 phosphorylation both before and after training compared with NBW. Despite exercise being performed at the same relative intensity (65% of V̇o2peak), the acute exercise response on AMPK Thr172, ACC2 Ser221, AMPKα2β2γ1, and AMPKα2β2γ3 activities, GS activity, and adenine nucleotides as well as hexokinase II mRNA levels were all reduced after exercise training. Increased exercise-induced muscle AMPK activation and ACC2 Ser221 phosphorylation in LBW subjects may indicate a more sensitive AMPK system in this population. Long-term exercise training may reduce the need for AMPK to control energy turnover during exercise. Thus, the remaining γ3-associated AMPK activation by acute exercise after exercise training might be sufficient to maintain cellular energy balance.

scholarly journals Effect of high-intensity exercise training on lactate/H+ transport capacity in human skeletal muscle

1999 ◽  
Vol 276 (2) ◽  
pp. E255-E261 ◽  
Author(s):  
Henriette Pilegaard ◽  
Kristian Domino ◽  
Thomas Noland ◽  
Carsten Juel ◽  
Ylva Hellsten ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
High Intensity ◽  
Human Skeletal Muscle ◽  
Knee Extensor ◽  
High Intensity Exercise ◽  
Vastus Lateralis Muscle ◽  
Transport Capacity ◽  
Intense Exercise ◽  
Giant Vesicles

The present study examined the effect of high-intensity exercise training on muscle sarcolemmal lactate/H+ transport and the monocarboxylate transporters (MCT1 and MCT4) as well as lactate and H+ release during intense exercise in humans. One-legged knee-extensor exercise training was performed for 8 wk, and biopsies were obtained from untrained and trained vastus lateralis muscle. The rate of lactate/H+ transport determined in sarcolemmal giant vesicles was 12% higher ( P < 0.05) in the trained than in untrained muscle ( n = 7). The content of MCT1 and MCT4 protein was also higher (76 and 32%, respectively; n = 4) in trained muscle. Release of lactate and H+ from the quadriceps muscle at the end of intense exhaustive knee-extensor exercise was similar in the trained and untrained leg, although the estimated muscle intracellular-to-interstitial gradients of lactate and H+ were lower ( P < 0.05) in the trained than in the untrained muscle. The present data show that intense exercise training can increase lactate/H+transport capacity in human skeletal muscle as well as improve the ability of the muscle to release lactate and H+ during contractions.

scholarly journals The influence of physical training on the angiopoietin and VEGF-A systems in human skeletal muscle

2007 ◽  
Vol 103 (3) ◽  
pp. 1012-1020 ◽  
Author(s):  
T. Gustafsson ◽  
H. Rundqvist ◽  
J. Norrbom ◽  
E. Rullman ◽  
E. Jansson ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Human Skeletal Muscle ◽  
Acute Exercise ◽  
Vastus Lateralis ◽  
Exercise Bout ◽  
Voluntary Exercise ◽  
Vastus Lateralis Muscle ◽  
Mrna Levels ◽  
Ki 67

Eleven subjects performed one-legged exercise four times per week for 5 wk. The subjects exercised one leg for 45 min with restricted blood flow (R leg), followed by exercise with the other leg at the same absolute workload with unrestricted blood flow (UR leg). mRNA and protein expression were measured in biopsies from the vastus lateralis muscle obtained at rest before the training period, after 10 days, and after 5 wk of training, as well as 120 min after the first and last exercise bouts. Basal Ang-2 and Tie-1 mRNA levels increased in both legs with training. The Ang-2-to-Ang-1 ratio increased to a greater extent in the R leg. The changes in Ang-2 mRNA were followed by similar changes at the protein level. In the R leg, VEGF-A mRNA expression responded transiently after acute exercise both before and after the 5-wk training program. Over the course of the exercise program, there was a concurrent increase in basal VEGF-A protein and VEGFR-2 mRNA in the R leg. Ki-67 mRNA showed a greater increase in the R leg and the protein was localized to the endothelial cells. In summary, the increased translation of VEGF-A is suggested to be caused by the short mRNA burst induced by each exercise bout. The concurrent increase in the Ang-2-to-Ang-1 ratio and the VEGF-expression combined with the higher level of Ki-67 mRNA in the R leg indicate that changes in these systems are of importance also in nonpathological angiogenic condition such as voluntary exercise in humans. It further establish that hypoxia/ischemia-related metabolic perturbation is likely to be involved as stimuli in this process in human skeletal muscle.

Sign in / Sign up

Export Citation Format

Share Document