scholarly journals Regulation of exercise-induced fiber type transformation, mitochondrial biogenesis, and angiogenesis in skeletal muscle

2011 ◽  
Vol 110 (1) ◽  
pp. 264-274 ◽  
Author(s):  
Zhen Yan ◽  
Mitsuharu Okutsu ◽  
Yasir N. Akhtar ◽  
Vitor A. Lira
Keyword(s):  
Skeletal Muscle ◽  
Mitochondrial Biogenesis ◽  
Contractile Activity ◽  
Fiber Type ◽  
Genetically Engineered ◽  
Type Transformation ◽  
Muscle Adaptations ◽  
Exercise Induced ◽  
Skeletal Muscle Adaptations ◽  
Muscle Contractile

Skeletal muscle exhibits superb plasticity in response to changes in functional demands. Chronic increases of skeletal muscle contractile activity, such as endurance exercise, lead to a variety of physiological and biochemical adaptations in skeletal muscle, including mitochondrial biogenesis, angiogenesis, and fiber type transformation. These adaptive changes are the basis for the improvement of physical performance and other health benefits. This review focuses on recent findings in genetically engineered animal models designed to elucidate the mechanisms and functions of various signal transduction pathways and gene expression programs in exercise-induced skeletal muscle adaptations.

scholarly journals PGC-1α plays a functional role in exercise-induced mitochondrial biogenesis and angiogenesis but not fiber-type transformation in mouse skeletal muscle

2010 ◽  
Vol 298 (3) ◽  
pp. C572-C579 ◽  
Author(s):  
Tuoyu Geng ◽  
Ping Li ◽  
Mitsuharu Okutsu ◽  
Xinhe Yin ◽  
Jyeyi Kwek ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Endurance Exercise ◽  
Mitochondrial Biogenesis ◽  
Knockout Mice ◽  
Functional Role ◽  
Fiber Type ◽  
Mitochondrial Morphology ◽  
Mouse Skeletal Muscle ◽  
Type Transformation ◽  
Exercise Induced

Endurance exercise stimulates peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) expression in skeletal muscle, and forced expression of PGC-1α changes muscle metabolism and exercise capacity in mice. However, it is unclear if PGC-1α is indispensible for endurance exercise-induced metabolic and contractile adaptations in skeletal muscle. In this study, we showed that endurance exercise-induced expression of mitochondrial enzymes (cytochrome oxidase IV and cytochrome c) and increases of platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31)-positive endothelial cells in skeletal muscle, but not IIb-to-IIa fiber-type transformation, were significantly attenuated in muscle-specific Pgc-1α knockout mice. Interestingly, voluntary running effectively restored the compromised mitochondrial integrity and superoxide dismutase 2 (SOD2) protein expression in skeletal muscle in Pgc-1α knockout mice. Thus, PGC-1α plays a functional role in endurance exercise-induced mitochondrial biogenesis and angiogenesis, but not IIb-to-IIa fiber-type transformation in mouse skeletal muscle, and the improvement of mitochondrial morphology and antioxidant defense in response to endurance exercise may occur independently of PGC-1α function. We conclude that PGC-1α is required for complete skeletal muscle adaptations induced by endurance exercise in mice.

Methylglyoxal reduces molecular responsiveness to 4 weeks of endurance exercise in mouse plantaris muscle

2022 ◽  
Author(s):  
Tatsuro Egawa ◽  
Takeshi Ogawa ◽  
Takumi Yokokawa ◽  
Kohei Kido ◽  
Katsumasa Goto ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Endurance Exercise ◽  
Mitochondrial Biogenesis ◽  
Insulin Signaling ◽  
Exercise Group ◽  
Voluntary Exercise ◽  
Plantaris Muscle ◽  
Muscle Adaptations ◽  
Exercise Induced ◽  
Skeletal Muscle Adaptations

Endurance exercise triggers skeletal muscle adaptations, including enhanced insulin signaling, glucose metabolism, and mitochondrial biogenesis. However, exercise-induced skeletal muscle adaptations may not occur in some cases, a condition known as exercise-resistance. Methylglyoxal (MG) is a highly reactive dicarbonyl metabolite and has detrimental effects on the body such as causing diabetic complications, mitochondrial dysfunction, and inflammation. This study aimed to clarify the effect of methylglyoxal on skeletal muscle molecular adaptations following endurance exercise. Mice were randomly divided into 4 groups (n = 12 per group): sedentary control group, voluntary exercise group, MG-treated group, and MG-treated with voluntary exercise group. Mice in the voluntary exercise group were housed in a cage with a running wheel, while mice in the MG-treated groups received drinking water containing 1% MG. Four weeks of voluntary exercise induced several molecular adaptations in the plantaris muscle, including increased expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1α), mitochondria complex proteins, toll-like receptor 4 (TLR4), 72-kDa heat shock protein (HSP72), hexokinase II, and glyoxalase 1; this also enhanced insulin-stimulated Akt Ser473 phosphorylation and citrate synthase activity. However, these adaptations were suppressed with MG treatment. In the soleus muscle, the exercise-induced increases in the expression of TLR4, HSP72, and advanced glycation end products receptor 1 were inhibited with MG treatment. These findings suggest that MG is a factor that inhibits endurance exercise-induced molecular responses including mitochondrial adaptations, insulin signaling activation, and the upregulation of several proteins related to mitochondrial biogenesis, glucose handling, and glycation in primarily fast-twitch skeletal muscle.

scholarly journals Pterostilbene Enhances Endurance Capacity via Promoting Skeletal Muscle Adaptations to Exercise Training in Rats

Molecules ◽  
2020 ◽  
Vol 25 (1) ◽  
pp. 186 ◽  
Author(s):  
Jiawei Zheng ◽  
Wujian Liu ◽  
Xiaohui Zhu ◽  
Li Ran ◽  
Hedong Lang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Mitochondrial Biogenesis ◽  
C2c12 Myotubes ◽  
Endurance Capacity ◽  
Muscle Adaptations ◽  
Slow Twitch ◽  
Slow Twitch Fibers ◽  
Skeletal Muscle Adaptations

It has been demonstrated that skeletal muscle adaptions, including muscle fibers transition, angiogenesis, and mitochondrial biogenesis are involved in the regular exercise-induced improvement of endurance capacity and metabolic status. Herein, we investigated the effects of pterostilbene (PST) supplementation on skeletal muscle adaptations to exercise training in rats. Six-week-old male Sprague Dawley rats were randomly divided into a sedentary control group (Sed), an exercise training group (Ex), and exercise training combined with 50 mg/kg PST (Ex + PST) treatment group. After 4 weeks of intervention, an exhaustive running test was performed, and muscle fiber type transformation, angiogenesis, and mitochondrial content in the soleus muscle were measured. Additionally, the effects of PST on muscle fiber transformation, paracrine regulation of angiogenesis, and mitochondrial function were tested in vitro using C2C12 myotubes. In vivo study showed that exercise training resulted in significant increases in time-to-exhaustion, the proportion of slow-twitch fibers, muscular angiogenesis, and mitochondrial biogenesis in rats, and these effects induced by exercise training could be augmented by PST supplementation. Moreover, the in vitro study showed that PST treatment remarkably promoted slow-twitch fibers formation, angiogenic factor expression, and mitochondrial function in C2C12 myotubes. Collectively, our results suggest that PST promotes skeletal muscle adaptations to exercise training thereby enhancing the endurance capacity.

Role of myokines in exercise and metabolism

2007 ◽  
Vol 103 (3) ◽  
pp. 1093-1098 ◽  
Author(s):  
Bente Klarlund Pedersen ◽  
Thorbjörn C. A. Åkerström ◽  
Anders R. Nielsen ◽  
Christian P. Fischer
Keyword(s):  
Skeletal Muscle ◽  
Skeletal Muscles ◽  
Contractile Activity ◽  
Endocrine Effects ◽  
Skeletal Muscle Function ◽  
The Past ◽  
Exercise Induced ◽  
Immune Changes ◽  
Muscle Contractile

During the past 20 yr, it has been well documented that exercise has a profound effect on the immune system. With the discovery that exercise provokes an increase in a number of cytokines, a possible link between skeletal muscle contractile activity and immune changes was established. For most of the last century, researchers sought a link between muscle contraction and humoral changes in the form of an “exercise factor,” which could mediate some of the exercise-induced metabolic changes in other organs such as the liver and the adipose tissue. We suggest that cytokines and other peptides that are produced, expressed, and released by muscle fibers and exert either paracrine or endocrine effects should be classified as “myokines.” Since the discovery of interleukin (IL)-6 release from contracting skeletal muscle, evidence has accumulated that supports an effect of IL-6 on metabolism. We suggested that muscle-derived IL-6 fulfils the criteria of an exercise factor and that such classes of cytokines should be named “myokines.” Interestingly, recent research demonstrates that skeletal muscles can produce and express cytokines belonging to distinctly different families. Thus skeletal muscle has the capacity to express several myokines. To date the list includes IL-6, IL-8, and IL-15, and contractile activity plays a role in regulating the expression of these cytokines in skeletal muscle. The present review focuses on muscle-derived cytokines, their regulation by exercise, and their possible roles in metabolism and skeletal muscle function and it discusses which cytokines should be classified as true myokines.

scholarly journals AQP4-Dependent Water Transport Plays a Functional Role in Exercise-Induced Skeletal Muscle Adaptations

PLoS ONE ◽  
2013 ◽  
Vol 8 (3) ◽  
pp. e58712 ◽  
Author(s):  
Davide Basco ◽  
Bert Blaauw ◽  
Francesco Pisani ◽  
Angelo Sparaneo ◽  
Grazia Paola Nicchia ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Water Transport ◽  
Functional Role ◽  
Muscle Adaptations ◽  
Exercise Induced ◽  
Skeletal Muscle Adaptations

scholarly journals PGC-1α regulation by exercise training and its influences on muscle function and insulin sensitivity

2010 ◽  
Vol 299 (2) ◽  
pp. E145-E161 ◽  
Author(s):  
Vitor A. Lira ◽  
Carley R. Benton ◽  
Zhen Yan ◽  
Arend Bonen
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Transgenic Mice ◽  
Mitochondrial Biogenesis ◽  
Therapeutic Potential ◽  
Fiber Type ◽  
Acid Oxidation ◽  
Physiological Limits ◽  
Exercise Induced

The peroxisome proliferator-activated receptor-γ (PPARγ) coactivator-1α (PGC-1α) is a major regulator of exercise-induced phenotypic adaptation and substrate utilization. We provide an overview of 1) the role of PGC-1α in exercise-mediated muscle adaptation and 2) the possible insulin-sensitizing role of PGC-1α. To these ends, the following questions are addressed. 1) How is PGC-1α regulated, 2) what adaptations are indeed dependent on PGC-1α action, 3) is PGC-1α altered in insulin resistance, and 4) are PGC-1α-knockout and -transgenic mice suitable models for examining therapeutic potential of this coactivator? In skeletal muscle, an orchestrated signaling network, including Ca2+-dependent pathways, reactive oxygen species (ROS), nitric oxide (NO), AMP-dependent protein kinase (AMPK), and p38 MAPK, is involved in the control of contractile protein expression, angiogenesis, mitochondrial biogenesis, and other adaptations. However, the p38γ MAPK/PGC-1α regulatory axis has been confirmed to be required for exercise-induced angiogenesis and mitochondrial biogenesis but not for fiber type transformation. With respect to a potential insulin-sensitizing role of PGC-1α, human studies on type 2 diabetes suggest that PGC-1α and its target genes are only modestly downregulated (≤34%). However, studies in PGC-1α-knockout or PGC-1α-transgenic mice have provided unexpected anomalies, which appear to suggest that PGC-1α does not have an insulin-sensitizing role. In contrast, a modest (∼25%) upregulation of PGC-1α, within physiological limits, does improve mitochondrial biogenesis, fatty acid oxidation, and insulin sensitivity in healthy and insulin-resistant skeletal muscle. Taken altogether, there is substantial evidence that the p38γ MAPK-PGC-1α regulatory axis is critical for exercise-induced metabolic adaptations in skeletal muscle, and strategies that upregulate PGC-1α, within physiological limits, have revealed its insulin-sensitizing effects.

Voluntary running induces fiber type-specific angiogenesis in mouse skeletal muscle

2004 ◽  
Vol 287 (5) ◽  
pp. C1342-C1348 ◽  
Author(s):  
Richard E. Waters ◽  
Svein Rotevatn ◽  
Ping Li ◽  
Brian H. Annex ◽  
Zhen Yan
Keyword(s):  
Skeletal Muscle ◽  
Endurance Training ◽  
Fiber Type ◽  
Capillary Density ◽  
Adult Skeletal Muscle ◽  
Heavy Chains ◽  
Type Transformation ◽  
Type Composition ◽  
Voluntary Running ◽  
Exercise Induced

Adult skeletal muscle undergoes adaptation in response to endurance exercise, including fast-to-slow fiber type transformation and enhanced angiogenesis. The purpose of this study was to determine the temporal and spatial changes in fiber type composition and capillary density in a mouse model of endurance training. Long-term voluntary running (4 wk) in C57BL/6 mice resulted in an approximately twofold increase in capillary density and capillary-to-fiber ratio in plantaris muscle as measured by indirect immunofluorescence with an antibody against the endothelial cell marker CD31 (466 ± 16 capillaries/mm2 and 0.95 ± 0.04 capillaries/fiber in sedentary control mice vs. 909 ± 55 capillaries/mm2 and 1.70 ± 0.04 capillaries/fiber in trained mice, respectively; P < 0.001). A significant increase in capillary-to-fiber ratio was present at day 7 with increased concentration of vascular endothelial growth factor (VEGF) in the muscle, before a significant increase in percentage of type IIa myofibers, suggesting that exercise-induced angiogenesis occurs first, followed by fiber type transformation. Further analysis with simultaneous staining of endothelial cells and isoforms of myosin heavy chains (MHCs) showed that the increase in capillary contact manifested transiently in type IIb + IId/x fibers at the time ( day 7) of significant increase in total capillary density. These findings suggest that endurance training induces angiogenesis in a subpopulation of type IIb + IId/x fibers before switching to type IIa fibers.

scholarly journals Differential activation of mTOR signaling by contractile activity in skeletal muscle

2003 ◽  
Vol 285 (5) ◽  
pp. R1086-R1090 ◽  
Author(s):  
Jascha D. Parkington ◽  
Adam P. Siebert ◽  
Nathan K. LeBrasseur ◽  
Roger A. Fielding
Keyword(s):  
Skeletal Muscle ◽  
Time Course ◽  
Contractile Activity ◽  
Fiber Type ◽  
Mtor Signaling ◽  
Type I ◽  
Fiber Types ◽  
Mtor Phosphorylation ◽  
Pkb Phosphorylation ◽  
Muscle Contractile

The cellular mechanisms by which contractile activity stimulates skeletal muscle hypertrophy are beginning to be elucidated and appear to include activation of the phosphatidylinositol 3-kinase signaling substrate mammalian target of rapamycin (mTOR). We examined the time course and location of mTOR phosphorylation in response to an acute bout of contractile activity. Rat hindlimb muscle contractile activity was elicited by high-frequency electrical stimulation (HFES) of the sciatic nerve. Plantaris (Pla), tibialis anterior (TA), and soleus (Sol) muscles from stimulated and control limbs were collected immediately or 6 h after stimulation. HFES resulted in mTOR phosphorylation immediately after (3.4 ± 0.9-fold, P < 0.01) contractile activity in Pla, whereas TA was unchanged compared with controls. mTOR phosphorylation remained elevated in Pla (3.6 ± 0.6-fold) and increased in TA (4.6 ± 0.9-fold, P < 0.05) 6 h after HFES. Interestingly, mTOR activation occurred predominantly in fibers expressing type IIa but not type I myosin heavy chain isoform. Furthermore, HFES induced modest ribosomal protein S6 kinase phosphorylation immediately after exercise in Pla (0.4 ± 0.1-fold, P < 0.05) but not TA and more markedly 6 h after in both Pla and TA (1.4 ± 0.4-fold vs. 2.4 ± 0.3-fold, respectively, P < 0.01). Akt/PKB phosphorylation was similar to controls at both time points. These results suggest that mTOR signaling is increased after a single bout of muscle contractile activity. Despite reports that mTOR is activated downstream of Akt/PKB, in this study, HFES induced mTOR signaling independent of Akt/PKB phosphorylation. Fiber type-dependent mTOR phosphorylation may be a molecular basis by which some fiber types are more susceptible to contraction-induced hypertrophy.

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