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.

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 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.

MicroRNA-23a has minimal effect on endurance exercise-induced adaptation of mouse skeletal muscle

2014 ◽  
Vol 467 (2) ◽  
pp. 389-398 ◽  
Author(s):  
Shogo Wada ◽  
Yoshio Kato ◽  
Shuji Sawada ◽  
Katsuji Aizawa ◽  
Jong-Hoon Park ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Endurance Exercise ◽  
Minimal Effect ◽  
Mouse Skeletal Muscle ◽  
Exercise Induced

Skeletal muscle adaptation in response to mechanical stress in p130cas−/− mice

2013 ◽  
Vol 304 (6) ◽  
pp. C541-C547 ◽  
Author(s):  
Takayuki Akimoto ◽  
Kanako Okuhira ◽  
Katsuji Aizawa ◽  
Shogo Wada ◽  
Hiroaki Honda ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Mechanical Stress ◽  
P38 Mapk ◽  
Fiber Type ◽  
Cellular Signaling ◽  
Mapk Signaling ◽  
Muscle Adaptation ◽  
Type Transformation ◽  
Exercise Induced ◽  
Specific Deletion

Mammalian skeletal muscles undergo adaptation in response to changes in the functional demands upon them, involving mechanical-stress-induced cellular signaling called “mechanotransduction.” We hypothesized that p130Cas, which is reported to act as a mechanosensor that transduces mechanical extension into cellular signaling, plays an important role in maintaining and promoting skeletal muscle adaptation in response to mechanical stress via the p38 MAPK signaling pathway. We demonstrate that muscle-specific p130Cas−/− mice express the contractile proteins normally in skeletal muscle. Furthermore, muscle-specific p130Cas−/− mice show normal mechanical-stress-induced muscle adaptation, including exercise-induced IIb-to-IIa muscle fiber type transformation and hypertrophy. Finally, we provide evidence that exercise-induced p38 MAPK signaling is not impaired by the muscle-specific deletion of p130Cas. We conclude that p130Cas plays a limited role in mechanical-stress-induced skeletal muscle adaptation.

scholarly journals An inducible knockout of Dicer in adult mice does not affect endurance exercise-induced muscle adaptation

2019 ◽  
Vol 316 (2) ◽  
pp. C285-C292 ◽  
Author(s):  
Satoshi Oikawa ◽  
Minjung Lee ◽  
Norio Motohashi ◽  
Seiji Maeda ◽  
Takayuki Akimoto
Keyword(s):  
Skeletal Muscle ◽  
Endurance Exercise ◽  
Citrate Synthase ◽  
Wheel Running ◽  
Fiber Type ◽  
Tamoxifen Treatment ◽  
Muscle Adaptation ◽  
Adult Skeletal Muscle ◽  
Significant Difference ◽  
Exercise Induced

The contractile and metabolic properties of adult skeletal muscle change in response to endurance exercise. The mechanisms of transcriptional regulation in exercise-induced skeletal muscle adaptation, including fiber-type switching and mitochondrial biogenesis, have been investigated intensively, whereas the role of microRNA (miRNA)-mediated posttranscriptional gene regulation is less well understood. We used tamoxifen-inducible Dicer1 knockout (iDicer KO) mice to reduce the global expression of miRNAs in adult skeletal muscle and subjected these mice to 2 wk of voluntary wheel running. Dicer mRNA expression was completely depleted in fast-twitch plantaris muscle after tamoxifen injection. However, several muscle-enriched miRNAs, including miR-1 and miR-133a, were reduced by only 30–50% in both the slow and fast muscles. The endurance exercise-induced changes that occurred for many parameters (i.e., fast-to-slow fiber-type switch and increases in succinate dehydrogenase, respiratory chain complex II, and citrate synthase activity) in wild type (WT) also occurred in the iDicer KO mice. Protein expression of myosin heavy chain IIa, peroxisome proliferator-activated receptor-γ coactivator-1α, and cytochrome c complex IV was also increased in the iDicer KO mice by the voluntary running. Furthermore, there was no significant difference in oxygen consumption rate in the isolated mitochondria between the WT and iDicer KO mice. These data indicate that muscle-enriched miRNAs were detectable even after 4 wk of tamoxifen treatment and there was no apparent specific endurance-exercise-induced muscle phenotype in the iDicer KO mice.

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