PGC-1α and PGC-1β have both similar and distinct effects on myofiber switching toward an oxidative phenotype

2006 ◽  
Vol 291 (4) ◽  
pp. E807-E816 ◽  
Author(s):  
Ole Hartvig Mortensen ◽  
Lis Frandsen ◽  
Peter Schjerling ◽  
Erica Nishimura ◽  
Niels Grunnet
Keyword(s):  
Skeletal Muscle ◽  
Enzymatic Activity ◽  
Muscle Fiber ◽  
Citrate Synthase ◽  
Fiber Type ◽  
Mrna Level ◽  
Creatine Kinase Activity ◽  
Negative Regulator ◽  
Peroxisome Proliferator ◽  
Mrna Levels

Peroxisome proliferator-activated receptor-γ coactivator-1α and -1β (PGC-1α and PGC-1β) were overexpressed by adenovirus-mediated gene transfer in cultures of primary rat skeletal muscle cells derived from neonatal myoblasts. Effects on muscle fiber type transition and metabolism were studied from days 5 to 22 of culture. PGC-1α and PGC-1β overexpression caused a three- to fourfold increase in mRNA level, a doubling of enzymatic activity of citrate synthase, a slight increase in short-chain acyl-CoA dehydrogenase mRNA, a doubling of the mRNA level, and a 30–50% increase in enzymatic activity of glyceraldehyde-3-phosphate dehydrogenase. Lactate dehydrogenase or creatine kinase activity was unchanged. PGC-1α enhanced glycogen buildup twofold at 5 or 25 mM glucose, whereas PGC-1β caused a decrease. Both PGC-1α and PGC-1β overexpression caused a faster maturation of myotubes, as seen by mRNA downregulation of the immature embryonal and perinatal myosin heavy-chain (MHC) isoforms. PGC-1α or PGC-1β overexpression enhanced mRNA of the slow oxidative-associated MHC isoform MHCIb and downregulated mRNA levels of the fast glycolytic-associated MHC isoforms MHCIIX and MHCIIB. Only PGC-1β overexpression caused an increase in mRNA of the intermediary fast oxidative-associated MHC isoform MHCIIA. PGC-1α or PGC-1β overexpression upregulated GLUT4 mRNA and downregulated myocyte enhancer factor 2C transcription factor mRNA; only PGC-1α overexpression caused an increase in the mRNA expression of TRB3, a negative regulator of insulin signaling. These results show that both PGC-1α and PGC-1β are involved in the regulation of skeletal muscle fiber transition and metabolism and that they have both overlapping and differing effects.

scholarly journals Overexpression of TRB3 in muscle alters muscle fiber type and improves exercise capacity in mice

2014 ◽  
Vol 306 (12) ◽  
pp. R925-R933 ◽  
Author(s):  
Ding An ◽  
Sarah J. Lessard ◽  
Taro Toyoda ◽  
Min-Young Lee ◽  
Ho-Jin Koh ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Exercise Capacity ◽  
Muscle Fiber ◽  
Wheel Running ◽  
Fiber Type ◽  
Muscle Fiber Type ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
Type I ◽  
Pronounced Increase

Increasing evidence suggests that TRB3, a mammalian homolog of Drosophila tribbles, plays an important role in cell growth, differentiation, and metabolism. In the liver, TRB3 binds and inhibits Akt activity, whereas in adipocytes, TRB3 upregulates fatty acid oxidation. In cultured muscle cells, TRB3 has been identified as a potential regulator of insulin signaling. However, little is known about the function and regulation of TRB3 in skeletal muscle in vivo. In the current study, we found that 4 wk of voluntary wheel running (6.6 ± 0.4 km/day) increased TRB3 mRNA by 1.6-fold and protein by 2.5-fold in the triceps muscle. Consistent with this finding, muscle-specific transgenic mice that overexpress TRB3 (TG) had a pronounced increase in exercise capacity compared with wild-type (WT) littermates (TG: 1,535 ± 283; WT: 644 ± 67 joules). The increase in exercise capacity in TRB3 TG mice was not associated with changes in glucose uptake or glycogen levels; however, these mice displayed a dramatic shift toward a more oxidative/fatigue-resistant (type I/IIA) muscle fiber type, including threefold more type I fibers in soleus muscles. Skeletal muscle from TRB3 TG mice had significantly decreased PPARα expression, twofold higher levels of miR208b and miR499, and corresponding increases in the myosin heavy chain isoforms Myh7 and Myb7b, which encode these microRNAs. These findings suggest that TRB3 regulates muscle fiber type via a peroxisome proliferator-activated receptor-α (PPAR-α)-regulated miR499/miR208b pathway, revealing a novel function for TRB3 in the regulation of skeletal muscle fiber type and exercise capacity.

Skeletal muscle myostatin mRNA expression is fiber-type specific and increases during hindlimb unloading

1999 ◽  
Vol 277 (2) ◽  
pp. R601-R606 ◽  
Author(s):  
Christian J. Carlson ◽  
Frank W. Booth ◽  
Scott E. Gordon
Keyword(s):  
Skeletal Muscle ◽  
Muscle Mass ◽  
Soleus Muscle ◽  
Fiber Type ◽  
Weight Bearing ◽  
Mrna Abundance ◽  
Hindlimb Unloading ◽  
Negative Regulator ◽  
Type I ◽  
Mrna Levels

Transgenic mice lacking a functional myostatin (MSTN) gene demonstrate greater skeletal muscle mass resulting from muscle fiber hypertrophy and hyperplasia (McPherron, A. C., A. M. Lawler, and S.-J. Lee. Nature 387: 83–90, 1997). Therefore, we hypothesized that, in normal mice, MSTN may act as a negative regulator of muscle mass. Specifically, we hypothesized that the predominately slow (type I) soleus muscle, which demonstrates greater atrophy than the fast (type II) gastrocnemius-plantaris complex (Gast/PLT), would show more elevation in MSTN mRNA abundance during hindlimb unloading (HU). Surprisingly, MSTN mRNA was not detectable in weight-bearing or HU soleus muscle, which atrophied 42% by the 7th day of HU in female ICR mice. In contrast, MSTN mRNA was present in weight-bearing Gast/PLT muscle and was significantly elevated (67%) at 1 day but not at 3 or 7 days of HU. However, the Gast/PLT muscle had only atrophied 17% by the 7th day of HU. Because the soleus is composed only of type I and IIa fibers, whereas the Gast/PLT expresses type IId/x and IIb in addition to type I and IIa, it was necessary to perform a more careful analysis of the relationship between MSTN mRNA levels and myosin heavy-chain (MHC) isoform expression (as a marker of fiber type). A significant correlation ( r = 0.725, P < 0.0005) was noted between the percentage of MHC isoform IIb expression and MSTN mRNA abundance in several muscles of the mouse hindlimb. These results indicate that MSTN expression is not strongly associated with muscle atrophy induced by HU; however, it is strongly associated with MHC isoform IIb expression in normal muscle.

scholarly journals Sex-specific alterations in mRNA level of key lipid metabolism enzymes in skeletal muscle of overweight and obese subjects following endurance exercise

2009 ◽  
Vol 36 (3) ◽  
pp. 149-157 ◽  
Author(s):  
Ira J. Smith ◽  
Kim M. Huffman ◽  
Michael T. Durheim ◽  
Brian D. Duscha ◽  
William E. Kraus
Keyword(s):  
Skeletal Muscle ◽  
Lipid Metabolism ◽  
Endurance Exercise ◽  
Regulatory Element ◽  
Mrna Level ◽  
Mrna Abundance ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Middle Aged ◽  
Metabolism Enzymes

Endurance exercise (EE) leads to beneficial alterations in skeletal muscle lipid metabolism in overweight and obese individuals; however, the mechanisms of these improvements are poorly understood. The primary goal of the current investigation was to test the hypothesis that long-term EE training (6 mo) leads to alterations in the mRNA abundance of key lipid metabolism enzymes in skeletal muscle of overweight and obese middle-aged women and men. A secondary aim of this study was to investigate the hypothesis that exercise-mediated adaptations in mRNA levels differ between women and men. The mRNA abundance of representative lipogenic and lipolytic genes from major lipid metabolism pathways, as well as representative lipogenic and lipolytic transcription factors, were determined by real-time PCR from skeletal muscle biopsies collected before and ∼24 h after the final bout of 6 mo of EE. Six months of EE led to increases in muscle lipoprotein lipase, peroxisome proliferator-activated receptor-γ coactivator-1α, carnitine palmitoyltransferase-1 β, diacylglycerol acyltransferase-1, and acid ceramidase mRNA in women, but not men. In contrast, in men, EE led to reductions in the mRNA content of the lipogenic factors sterol regulatory element binding protein-1c and serine palmitoyl transferase. These data suggest that EE-mediated alterations in the abundance of the lipid metabolism genes studied here are fundamentally different between overweight and obese middle-aged women and men. Future studies should determine whether these adaptations in mRNA levels translate into changes in protein function.

scholarly journals Differential Expression of NADPH Oxidases Depends on Skeletal Muscle Fiber Type in Rats

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Adriano César Carneiro Loureiro ◽  
Igor Coutinho do Rêgo-Monteiro ◽  
Ruy A. Louzada ◽  
Victor Hugo Ortenzi ◽  
Angélica Ponte de Aguiar ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Oxygen Consumption ◽  
Muscle Fiber ◽  
Fiber Type ◽  
Skeletal Muscle Fiber ◽  
Muscle Fiber Type ◽  
Mrna Levels ◽  
Protein Thiol ◽  
Nadph Oxidases ◽  
Reactive Protein

NADPH oxidases (NOX) are important sources of reactive oxygen species (ROS) in skeletal muscle, being involved in excitation-contraction coupling. Thus, we aimed to investigate if NOX activity and expression in skeletal muscle are fiber type specific and the possible contribution of this difference to cellular oxidative stress. Oxygen consumption rate, NOX activity and mRNA levels, and the activity of catalase (CAT), glutathione peroxidase (GPX), and superoxide dismutase (SOD), as well as the reactive protein thiol levels, were measured in the soleus (SOL), red gastrocnemius (RG), and white gastrocnemius (WG) muscles of rats. RG showed higher oxygen consumption flow than SOL and WG, while SOL had higher oxygen consumption than WG. SOL showed higher NOX activity, as well as NOX2 and NOX4 mRNA levels, antioxidant enzymatic activities, and reactive protein thiol contents when compared to WG and RG. NOX activity and NOX4 mRNA levels as well as antioxidant enzymatic activities were higher in RG than in WG. Physical exercise increased NOX activity in SOL and RG, specifically NOX2 mRNA levels in RG and NOX4 mRNA levels in SOL. In conclusion, we demonstrated that NOX activity and expression differ according to the skeletal muscle fiber type, as well as antioxidant defense.

scholarly journals NFATc1 Controls Skeletal Muscle Fiber Type and Is a Negative Regulator of MyoD Activity

Cell Reports ◽  
2014 ◽  
Vol 8 (6) ◽  
pp. 1639-1648 ◽  
Author(s):  
Melissa L. Ehlers ◽  
Barbara Celona ◽  
Brian L. Black
Keyword(s):  
Skeletal Muscle ◽  
Muscle Fiber ◽  
Fiber Type ◽  
Skeletal Muscle Fiber ◽  
Negative Regulator ◽  
Muscle Fiber Type

Mitochondrial biogenesis during skeletal muscle regeneration

2002 ◽  
Vol 282 (4) ◽  
pp. E802-E809 ◽  
Author(s):  
Stéphanie Duguez ◽  
Léonard Féasson ◽  
Christian Denis ◽  
Damien Freyssenet
Keyword(s):  
Skeletal Muscle ◽  
Mitochondrial Biogenesis ◽  
Transcriptional Activation ◽  
Muscle Regeneration ◽  
Citrate Synthase ◽  
Mrna Level ◽  
Skeletal Muscle Regeneration ◽  
Nuclear Antigen ◽  
Peroxisome Proliferator ◽  
Sprague Dawley

Myogenesis requires energy production for the execution of a number of regulatory and biosynthesis events. We hypothesized that mitochondrial biogenesis would be stimulated during skeletal muscle regeneration. Tibialis anterior muscles of male Sprague-Dawley rats were injected with 0.75% bupivacaine and removed at 3, 5, 7, 10, 14, 21, or 35 days after injection ( n = 5–7/group). Two main periods emerged from the histochemical analyses of muscle sections and the expression of proliferating cell nuclear antigen, desmin, and creatine phosphokinase: 1) activation/proliferation of satellite cells ( days 3–14) and 2) differentiation into muscle fibers ( days 5–35). The onset of muscle differentiation was accompanied by a marked stimulation of mitochondrial biogenesis, as indicated by a nearly fivefold increase in citrate synthase activity and state 3 rate of respiration between days 5 and 10. Peroxisome proliferator-activated receptor-γ coactivator-1 (PGC-1) mRNA level and mitochondrial transcription factor A (mtTFA) protein level peaked on day 10 concurrently with the state 3 rate of respiration. Therefore, transcriptional activation by PGC-1 and mtTFA may be one of the mechanisms regulating mitochondrial biogenesis in regenerating skeletal muscle. Taken together, our results suggest that mitochondrial biogenesis may be an important regulatory event during muscle regeneration.

Strength, power, fiber types, and mRNA expression in trained men and women with different ACTN3 R577X genotypes

2009 ◽  
Vol 106 (3) ◽  
pp. 959-965 ◽  
Author(s):  
Barbara Norman ◽  
Mona Esbjörnsson ◽  
Håkan Rundqvist ◽  
Ted Österlund ◽  
Ferdinand von Walden ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Fiber ◽  
Fiber Type ◽  
Muscle Fiber Types ◽  
Vastus Lateralis Muscle ◽  
Fiber Types ◽  
Mrna Levels ◽  
Men And Women ◽  
Fiber Type Composition ◽  
Type Composition

α-Actinins are structural proteins of the Z-line. Human skeletal muscle expresses two α-actinin isoforms, α-actinin-2 and α-actinin-3, encoded by their respective genes ACTN2 and ACTN3. ACTN2 is expressed in all muscle fiber types, while only type II fibers, and particularly the type IIb fibers, express ACTN3. ACTN3 (R577X) polymorphism results in loss of α-actinin-3 and has been suggested to influence skeletal muscle function. The X allele is less common in elite sprint and power athletes than in the general population and has been suggested to be detrimental for performance requiring high power. The present study investigated the association of ACTN3 genotype with muscle power during 30-s Wingate cycling in 120 moderately to well-trained men and women and with knee extensor strength and fatigability in a subset of 21 men performing isokinetic exercise. Muscle biopsies were obtained from the vastus lateralis muscle to determine fiber-type composition and ACTN2 and ACTN3 mRNA levels. Peak and mean power and the torque-velocity relationship and fatigability output showed no difference across ACTN3 genotypes. Thus this study suggests that R577X polymorphism in ACTN3 is not associated with differences in power output, fatigability, or force-velocity characteristics in moderately trained individuals. However, repeated exercise bouts prompted an increase in peak torque in RR but not in XX genotypes, suggesting that ACTN3 genotype may modulate responsiveness to training. Our data further suggest that α-actinins do not play a significant role in determining muscle fiber-type composition. Finally, we show that ACTN2 expression is affected by the content of α-actinin-3, which implies that α-actinin-2 may compensate for the lack of α-actinin-3 and hence counteract the phenotypic consequences of the deficiency.

Aerobic exercise training improves Ca2+ handling and redox status of skeletal muscle in mice

2010 ◽  
Vol 235 (4) ◽  
pp. 497-505 ◽  
Author(s):  
Julio C B Ferreira ◽  
Aline V Bacurau ◽  
Carlos R Bueno ◽  
Telma C Cunha ◽  
Leonardo Y Tanaka ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Muscle Fiber ◽  
Citrate Synthase ◽  
Fiber Type ◽  
Redox Status ◽  
Related Protein ◽  
Cellular Redox ◽  
Running Performance ◽  
Protein Levels

Exercise training is known to promote relevant changes in the properties of skeletal muscle contractility toward powerful fibers. However, there are few studies showing the effect of a well-established exercise training protocol on Ca2+ handling and redox status in skeletal muscles with different fiber-type compositions. We have previously standardized a valid and reliable protocol to improve endurance exercise capacity in mice based on maximal lactate steady-state workload (MLSSw). The aim of this study was to investigate the effect of exercise training, performed at MLSSw, on the skeletal muscle Ca2+ handling-related protein levels and cellular redox status in soleus and plantaris. Male C57BL/6J mice performed treadmill training at MLSSw over a period of eight weeks. Muscle fiber-typing was determined by myosin ATPase histochemistry, citrate synthase activity by spectrophotometric assay, Ca2+ handling-related protein levels by Western blot and reduced to oxidized glutathione ratio (GSH:GSSG) by high-performance liquid chromatography. Trained mice displayed higher running performance and citrate synthase activity compared with untrained mice. Improved running performance in trained mice was paralleled by fast-to-slow fiber-type shift and increased capillary density in both plantaris and soleus. Exercise training increased dihydropyridine receptor (DHPR) α2 subunit, ryanodine receptor and Na+/Ca2+ exchanger levels in plantaris and soleus. Moreover, exercise training elevated DHPR β1 subunit and sarcoplasmic reticulum Ca2+-ATPase (SERCA) 1 levels in plantaris and SERCA2 levels in soleus of trained mice. Skeletal muscle GSH content and GSH:GSSG ratio was increased in plantaris and soleus of trained mice. Taken together, our findings indicate that MLSSw exercise-induced better running performance is, in part, due to increased levels of proteins involved in skeletal muscle Ca2+ handling, whereas this response is partially dependent on specificity of skeletal muscle fiber-type composition. Finally, we demonstrated an augmented cellular redox status and GSH antioxidant capacity in trained mice.

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