scholarly journals The Molecular Adaptive Responses of Skeletal Muscle to High-Intensity Exercise/Training and Hypoxia

Antioxidants ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 656 ◽  
Author(s):  
Jia Li ◽  
Yanchun Li ◽  
Muhammed M. Atakan ◽  
Jujiao Kuang ◽  
Yang Hu ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
High Intensity ◽  
Hypoxia Inducible Factor ◽  
High Intensity Exercise ◽  
Peroxisome Proliferator ◽  
Adaptive Responses ◽  
Peroxisome Proliferator Activated Receptor ◽  
Anti Inflammatory ◽  
Inflammatory Signalling

High-intensity exercise/training, especially interval exercise/training, has gained popularity in recent years. Hypoxic training was introduced to elite athletes half a century ago and has recently been adopted by the general public. In the current review, we have summarised the molecular adaptive responses of skeletal muscle to high-intensity exercise/training, focusing on mitochondrial biogenesis, angiogenesis, and muscle fibre composition. The literature suggests that (peroxisome proliferator-activated receptor gamma coactivator 1-alpha) PGC-1α, vascular endothelial growth factor (VEGF), and hypoxia-inducible factor 1-alpha (HIF1-α) might be the main mediators of skeletal muscle adaptations to high-intensity exercises in hypoxia. Exercise is known to be anti-inflammatory, while the effects of hypoxia on inflammatory signalling are more complex. The anti-inflammatory effects of a single session of exercise might result from the release of anti-inflammatory myokines and other cytokines, as well as the downregulation of Toll-like receptor signalling, while training-induced anti-inflammatory effects may be due to reductions in abdominal and visceral fat (which are main sources of pro-inflammatory cytokines). Hypoxia can lead to inflammation, and inflammation can result in tissue hypoxia. However, the hypoxic factor HIF1-α is essential for preventing excessive inflammation. Disease-induced hypoxia is related to an upregulation of inflammatory signalling, but the effects of exercise-induced hypoxia on inflammation are less conclusive. The effects of high-intensity exercise under hypoxia on skeletal muscle molecular adaptations and inflammatory signalling have not been fully explored and are worth investigating in future studies. Understanding these effects will lead to a more comprehensive scientific basis for maximising the benefits of high-intensity exercise.

scholarly journals Skeletal muscle PGC-1β signaling is sufficient to drive an endurance exercise phenotype and to counteract components of detraining in mice

2017 ◽  
Vol 312 (5) ◽  
pp. E394-E406 ◽  
Author(s):  
Samuel Lee ◽  
Teresa C. Leone ◽  
Lisa Rogosa ◽  
John Rumsey ◽  
Julio Ayala ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Early Stage ◽  
Peroxisome Proliferator ◽  
Disuse Atrophy ◽  
Proof Of Concept ◽  
Peroxisome Proliferator Activated Receptor ◽  
Muscle Disuse ◽  
Training Response

Peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α and -1β serve as master transcriptional regulators of muscle mitochondrial functional capacity and are capable of enhancing muscle endurance when overexpressed in mice. We sought to determine whether muscle-specific transgenic overexpression of PGC-1β affects the detraining response following endurance training. First, we established and validated a mouse exercise-training-detraining protocol. Second, using multiple physiological and gene expression end points, we found that PGC-1β overexpression in skeletal muscle of sedentary mice fully recapitulated the training response. Lastly, PGC-1β overexpression during the detraining period resulted in partial prevention of the detraining response. Specifically, an increase in the plateau at which O2 uptake (V̇o2) did not change from baseline with increasing treadmill speed [peak V̇o2 (ΔV̇o2max)] was maintained in trained mice with PGC-1β overexpression in muscle 6 wk after cessation of training. However, other detraining responses, including changes in running performance and in situ half relaxation time (a measure of contractility), were not affected by PGC-1β overexpression. We conclude that while activation of muscle PGC-1β is sufficient to drive the complete endurance phenotype in sedentary mice, it only partially prevents the detraining response following exercise training, suggesting that the process of endurance detraining involves mechanisms beyond the reversal of muscle autonomous mechanisms involved in endurance fitness. In addition, the protocol described here should be useful for assessing early-stage proof-of-concept interventions in preclinical models of muscle disuse atrophy.

Effect of short-term, high-intensity exercise training on human skeletal muscle citrate synthase maximal activity: single versus multiple bouts per session

2019 ◽  
Vol 44 (12) ◽  
pp. 1391-1394
Author(s):  
Martin J. MacInnis ◽  
Lauren E. Skelly ◽  
F. Elizabeth Godkin ◽  
Brian J. Martin ◽  
Thomas R. Tripp ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
High Intensity ◽  
Human Skeletal Muscle ◽  
Citrate Synthase ◽  
Vastus Lateralis ◽  
Maximal Activity ◽  
High Intensity Exercise ◽  
Short Term ◽  
Significant Difference

The legs of 9 men (age 21 ± 2 years, 45 ± 4 mL/(kg·min)) were randomly assigned to complete 6 sessions of high-intensity exercise training, involving either one or four 5-min bouts of counterweighted, single-leg cycling. Needle biopsies from vastus lateralis revealed that citrate synthase maximal activity increased after training in the 4-bout group (p = 0.035) but not the 1-bout group (p = 0.10), with a significant difference between groups post-training (13%, p = 0.021). Novelty Short-term training using brief intense exercise requires multiple bouts per session to increase mitochondrial content in human skeletal muscle.

Effect of exercise intensity and AICAR on isoform-specific expressions of murine skeletal muscle PGC-1α mRNA: a role of β2-adrenergic receptor activation

2011 ◽  
Vol 300 (2) ◽  
pp. E341-E349 ◽  
Author(s):  
Miki Tadaishi ◽  
Shinji Miura ◽  
Yuko Kai ◽  
Emi Kawasaki ◽  
Keiichi Koshinaka ◽  
...  
Keyword(s):  
Exercise Intensity ◽  
High Intensity ◽  
Adrenergic Receptor ◽  
Skeletal Muscles ◽  
Receptor Activation ◽  
High Intensity Exercise ◽  
Treadmill Running ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Exercise Induced

There are three isoforms of peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) mRNA, which promotes mitochondrial biogenesis in skeletal muscles. Compared with PGC-1α-a mRNA, PGC-1α-b or PGC-1α-c mRNA is transcribed by a different exon 1 of the PGC-1α gene. In this study, effects of exercise intensity and 5-aminoimidazole-4-carboxamide-1β-d-ribofuranoside (AICAR) on isoform-specific expressions of PGC-1α were investigated. All isoforms were increased in proportion to exercise intensity of treadmill running (10–30 m/min for 30 min). Preinjection of β2-adrenergic receptor (AR) antagonist (ICI 118551) inhibited the increase in PGC-1α-b and PGC-1α-c mRNAs, but not the increase in PGC-1α-a mRNA, in response to high-intensity exercise. Although high-intensity exercise activated α2-AMP-activated protein kinase (α2-AMPK) in skeletal muscles, inactivation of α2-AMPK activity did not affect high-intensity exercise-induced mRNA expression of all PGC-1α isoforms, suggesting that activation of α2-AMPK is not mandatory for an increase in PGC-1α mRNA by high-intensity exercise. A single injection in mice of AICAR, an AMPK activator, increased mRNAs of all PGC-1α isoforms. AICAR increased blood catecholamine concentrations, and preinjection of β2-AR antagonist inhibited the increase in PGC-1α-b and PGC-1α-c mRNAs but not the increase in PGC-1α-a mRNA. Direct exposure of epitrochlearis muscle to AICAR increased PGC-1α-a but not the -b isoform. These data indicate that exercise-induced PGC-1α expression was dependent on the intensity of exercise. Exercise or AICAR injection increased PGC-1α-b and PGC-1α-c mRNAs via β2-AR activation, whereas high-intensity exercise increased PGC-1α-a expression by a multiple mechanism in which α2-AMPK is one of the signaling pathways.

scholarly journals Preservation of skeletal muscle mitochondrial content in older adults: relationship between mitochondria, fibre type and high-intensity exercise training

2017 ◽  
Vol 595 (11) ◽  
pp. 3345-3359 ◽  
Author(s):  
Victoria L. Wyckelsma ◽  
Itamar Levinger ◽  
Michael J. McKenna ◽  
Luke E. Formosa ◽  
Michael T. Ryan ◽  
...  
Keyword(s):  
Older Adults ◽  
Skeletal Muscle ◽  
Exercise Training ◽  
High Intensity ◽  
Fibre Type ◽  
High Intensity Exercise ◽  
Mitochondrial Content

scholarly journals AMPK and PPARβ positive feedback loop regulates endurance exercise training-mediated GLUT4 expression in skeletal muscle

2019 ◽  
Vol 316 (5) ◽  
pp. E931-E939 ◽  
Author(s):  
Jin-Ho Koh ◽  
Chad R. Hancock ◽  
Dong-Ho Han ◽  
John O. Holloszy ◽  
K. Sreekumaran Nair ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Glucose Uptake ◽  
Glucose Transporter ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Glut4 Expression ◽  
Amp Activated Protein Kinase ◽  
Response To Exercise ◽  
Glucose Transporter Type 4

The objective of this study is to determine whether AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α), or peroxisome proliferator-activated receptor β (PPARβ) can independently mediate the increase of glucose transporter type 4 (GLUT4) expression that occurs in response to exercise training. We found that PPARβ can regulate GLUT4 expression without PGC-1α. We also found AMPK and PPARβ are important for maintaining normal physiological levels of GLUT4 protein in the sedentary condition as well following exercise training. However, AMPK and PPARβ are not essential for the increase in GLUT4 protein expression that occurs in response to exercise training. We discovered that AMPK activation increases PPARβ via myocyte enhancer factor 2A (MEF2A), which acted as a transcription factor for PPARβ. Furthermore, exercise training increases the cooperation of AMPK and PPARβ to regulate glucose uptake. In conclusion, cooperation between AMPK and PPARβ via NRF-1/MEF2A pathway enhances the exercise training mediated adaptive increase in GLUT4 expression and subsequent glucose uptake in skeletal muscle.

Mechanisms of calcium-induced mitochondrial biogenesis and GLUT4 synthesis

2007 ◽  
Vol 32 (5) ◽  
pp. 840-845 ◽  
Author(s):  
David C. Wright
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Mitochondrial Biogenesis ◽  
Glucose Transporter ◽  
Mitochondrial Protein ◽  
Mitogen Activated Protein Kinase ◽  
Peroxisome Proliferator ◽  
Adaptive Responses ◽  
Peroxisome Proliferator Activated Receptor ◽  
Skeletal Muscle Insulin Resistance

Regularly performed aerobic exercise leads to increases in skeletal muscle mitochondria and glucose transporter 4 (GLUT4) protein content, resulting in an enhanced capacity to oxidize substrates and improvements in insulin- and contraction-mediated glucose uptake. Although the specific mechanisms governing these adaptive responses have not been fully elucidated, accumulating evidence suggests that the increase in cytosolic Ca2+ that occurs with each wave of sacrolemmal depolarization is a key component of these processes. Treating L6 muscle cells with agents that increase Ca2+ without causing reductions in ~P or the activation of 5′-AMP-activated protein kinase leads to increases in GLUT4 and mitochondrial protein contents. This effect is likely controlled through calcium/calmodulin-dependent protein kinase (CaMK), since KN93, a specific CaMK inhibitor, blocks these adaptive responses. Recent findings provide evidence that the activation of p38 mitogen-activated protein kinase (MAPK) is involved in the pathway through which Ca2+/CaMK mediates mitochondrial and GLUT4 biogenesis. p38 MAPK initiates GLUT4 and mitochondrial biogenesis through the activation      of transcription factors and transcriptional coactivators such as myocyte enhancer factor 2 (MEF2) and peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α). Subsequent increases in the content of these proteins further enhance Ca2+-induced GLUT4 and mitochondrial biogenesis. Since decreases in mitochondrial and GLUT4 contents are associated with skeletal muscle insulin resistance, an understanding of the mechanisms by which these processes can be normalized will aid in the prevention and treatment of type 2 diabetes.

scholarly journals Effects of short-term endurance exercise training on acute doxorubicin-induced FoxO transcription in cardiac and skeletal muscle

2014 ◽  
Vol 117 (3) ◽  
pp. 223-230 ◽  
Author(s):  
Andreas N. Kavazis ◽  
Ashley J. Smuder ◽  
Scott K. Powers
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Endurance Exercise ◽  
Skeletal Muscles ◽  
Target Genes ◽  
Ring Finger ◽  
Peroxisome Proliferator ◽  
Short Term ◽  
Peroxisome Proliferator Activated Receptor ◽  
The Impact

Doxorubicin (DOX) is a potent antitumor agent used in cancer treatment. Unfortunately, DOX can induce myopathy in both cardiac and skeletal muscle, which limits its clinical use. Importantly, exercise training has been shown to protect against DOX-mediated cardiac and skeletal muscle myopathy. However, the mechanisms responsible for this exercise-induced muscle protection remain elusive. These experiments tested the hypothesis that short-term exercise training protects against acute DOX-induced muscle toxicity, in part, due to decreased forkhead-box O (FoxO) transcription of atrophy genes. Rats ( n = 6 per group) were assigned to sedentary or endurance exercise-trained groups and paired with either placebo or DOX treatment. Gene expression and protein abundance were measured in both cardiac and skeletal muscles to determine the impact of DOX and exercise on FoxO gene targets. Our data demonstrate that DOX administration amplified FoxO1 and FoxO3 mRNA expression and increased transcription of FoxO target genes [i.e., atrogin-1/muscle atrophy F-box (MaFbx), muscle ring finger-1 (MuRF-1), and BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3)] in heart and soleus muscles. Importantly, exercise training protected against DOX-induced increases of FoxO1 and MuRF-1 in cardiac muscle and also prevented the rise of FoxO3, MuRF-1, and BNIP3 in soleus muscle. Furthermore, our results indicate that exercise increased peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α) in both the heart and soleus muscles. This is important because increased PGC-1α expression is known to suppress FoxO activity resulting in reduced expression of FoxO target genes. Together, these results are consistent with the hypothesis that exercise training protects against DOX-induced myopathy in both heart (FoxO1 and MuRF-1) and skeletal muscles (FoxO3, MuRF-1, and BNIP3).

scholarly journals Novel, high-intensity exercise prescription improves muscle mass, mitochondrial function, and physical capacity in individuals with Parkinson's disease

2014 ◽  
Vol 116 (5) ◽  
pp. 582-592 ◽  
Author(s):  
Neil A. Kelly ◽  
Matthew P. Ford ◽  
David G. Standaert ◽  
Ray L. Watts ◽  
C. Scott Bickel ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Exercise Training ◽  
Muscle Tissue ◽  
High Intensity ◽  
Physical Capacity ◽  
High Intensity Exercise ◽  
Type I ◽  
Type Ii

We conducted, in persons with Parkinson's disease (PD), a thorough assessment of neuromotor function and performance in conjunction with phenotypic analyses of skeletal muscle tissue, and further tested the adaptability of PD muscle to high-intensity exercise training. Fifteen participants with PD (Hoehn and Yahr stage 2–3) completed 16 wk of high-intensity exercise training designed to simultaneously challenge strength, power, endurance, balance, and mobility function. Skeletal muscle adaptations ( P < 0.05) to exercise training in PD included myofiber hypertrophy (type I: +14%, type II: +36%), shift to less fatigable myofiber type profile, and increased mitochondrial complex activity in both subsarcolemmal and intermyofibrillar fractions (I: +45–56%, IV: +39–54%). These adaptations were accompanied by a host of functional and clinical improvements ( P < 0.05): total body strength (+30–56%); leg power (+42%); single leg balance (+34%); sit-to-stand motor unit activation requirement (−30%); 6-min walk (+43 m), Parkinson's Disease Quality of Life Scale (PDQ-39, −7.8pts); Unified Parkinson's Disease Rating Scale (UPDRS) total (−5.7 pts) and motor (−2.7 pts); and fatigue severity (−17%). Additionally, PD subjects in the pretraining state were compared with a group of matched, non-PD controls (CON; did not exercise). A combined assessment of muscle tissue phenotype and neuromuscular function revealed a higher distribution and larger cross-sectional area of type I myofibers and greater type II myofiber size heterogeneity in PD vs. CON ( P < 0.05). In conclusion, persons with moderately advanced PD adapt to high-intensity exercise training with favorable changes in skeletal muscle at the cellular and subcellular levels that are associated with improvements in motor function, physical capacity, and fatigue perception.

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