scholarly journals Agonists of the Peroxisome Proliferator–Activated Receptor Alpha Induce a Fiber-Type–Selective Transcriptional Response in Rat Skeletal Muscle

2006 ◽  
Vol 92 (2) ◽  
pp. 578-586 ◽  
Author(s):  
Angus T. De Souza ◽  
Paul D. Cornwell ◽  
Xudong Dai ◽  
Michelle J. Caguyong ◽  
Roger G. Ulrich
Keyword(s):  
Skeletal Muscle ◽  
Fiber Type ◽  
Transcriptional Response ◽  
Peroxisome Proliferator ◽  
Rat Skeletal Muscle ◽  
Peroxisome Proliferator Activated Receptor ◽  
Receptor Alpha

scholarly journals Remodeling of calcium handling in skeletal muscle through PGC-1α: impact on force, fatigability, and fiber type

2012 ◽  
Vol 302 (1) ◽  
pp. C88-C99 ◽  
Author(s):  
Serge Summermatter ◽  
Raphael Thurnheer ◽  
Gesa Santos ◽  
Barbara Mosca ◽  
Oliver Baum ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Calcium Release ◽  
Ex Vivo ◽  
Fiber Type ◽  
Force Production ◽  
Calcium Handling ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Calcium Clearance

Regular endurance exercise remodels skeletal muscle, largely through the peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α). PGC-1α promotes fiber type switching and resistance to fatigue. Intracellular calcium levels might play a role in both adaptive phenomena, yet a role for PGC-1α in the adaptation of calcium handling in skeletal muscle remains unknown. Using mice with transgenic overexpression of PGC-1α, we now investigated the effect of PGC-1α on calcium handling in skeletal muscle. We demonstrate that PGC-1α induces a quantitative reduction in calcium release from the sarcoplasmic reticulum by diminishing the expression of calcium-releasing molecules. Concomitantly, maximal muscle force is reduced in vivo and ex vivo. In addition, PGC-1α overexpression delays calcium clearance from the myoplasm by interfering with multiple mechanisms involved in calcium removal, leading to higher myoplasmic calcium levels following contraction. During prolonged muscle activity, the delayed calcium clearance might facilitate force production in mice overexpressing PGC-1α. Our results reveal a novel role of PGC-1α in altering the contractile properties of skeletal muscle by modulating calcium handling. Importantly, our findings indicate PGC-1α to be both down- as well as upstream of calcium signaling in this tissue. Overall, our findings suggest that in the adaptation to chronic exercise, PGC-1α reduces maximal force, increases resistance to fatigue, and drives fiber type switching partly through remodeling of calcium transients, in addition to promoting slow-type myofibrillar protein expression and adequate energy supply.

scholarly journals Combined effects of resistance training and calorie restriction on mitochondrial fusion and fission proteins in rat skeletal muscle

2016 ◽  
Vol 121 (3) ◽  
pp. 806-810 ◽  
Author(s):  
Yu Kitaoka ◽  
Koichi Nakazato ◽  
Riki Ogasawara
Keyword(s):  
Skeletal Muscle ◽  
Resistance Training ◽  
Calorie Restriction ◽  
Mitochondrial Biogenesis ◽  
Muscle Hypertrophy ◽  
Mitochondrial Fusion ◽  
Peroxisome Proliferator ◽  
Rat Skeletal Muscle ◽  
Muscle Weight ◽  
Peroxisome Proliferator Activated Receptor

Recent studies have demonstrated that resistance exercise leads not only to muscle hypertrophy, but it also improves mitochondrial function. Because calorie restriction (CR) has been suggested as a way to induce mitochondrial biogenesis, we examined the effects of resistance training with or without CR on muscle weight and key mitochondrial parameters in rat skeletal muscle. Four weeks of resistance training (thrice/wk) resulted in increased gastrocnemius muscle weight by 14% in rats fed ad libitum (AL). The degree of muscle-weight increase via resistance training was lower in rats with CR (7.4%). CR showed no effect on phosphorylation of mammalian target of rapamycin (mTOR) signaling proteins rpS6 and ULK1. Our results revealed that CR resulted in elevated levels of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) protein, a known master regulator of mitochondrial biogenesis. Resistance training alone also resulted in increased PGC-1α levels in skeletal muscle. The magnitude of the increase in PGC-1α was similar in rats in both the CR and AL groups. Moreover, we found that resistance training with CR resulted in elevated levels of proteins involved in mitochondrial fusion (Opa1 and Mfn1), and oxidative phosphorylation, whereas there was no effect of CR on the fission-regulatory proteins Fis1 and Drp1. These results indicate that CR attenuates resistance training-induced muscle hypertrophy, and that it may enhance mitochondrial adaptations in skeletal muscle.

scholarly journals Localization and Regulation of the N Terminal Splice Variant of PGC-1αin Adult Skeletal Muscle Fibers

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Tiansheng Shen ◽  
Yewei Liu ◽  
Martin F. Schneider
Keyword(s):  
Skeletal Muscle ◽  
Splice Variant ◽  
Nuclear Export ◽  
Fiber Type ◽  
Muscle Fibers ◽  
Nuclear Accumulation ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Adult Skeletal Muscle ◽  
Skeletal Muscle Fibers

The transcriptional coactivator peroxisome proliferator-activated receptorγcoactivator 1α(PGC-1α) regulates expression of genes for metabolism and muscle fiber type. Recently, a novel splice variant of PGC-1α(NT-PGC-1α, amino acids 1–270) was cloned and found to be expressed in muscle. Here we use Flag-tagged NT-PGC-1αto examine the subcellular localization and regulation of NT-PGC-1αin skeletal muscle fibers. Flag-NT-PGC-1αis located predominantly in the myoplasm. Nuclear NT-PGC-1αcan be increased by activation of protein kinase A. Activation of p38 MAPK by muscle activity or of AMPK had no effect on the subcellular distribution of NT-PGC-1α. Inhibition of CRM1-mediated export only caused relatively slow nuclear accumulation of NT-PGC-1α, indicating that nuclear export of NT-PGC-1αmay be mediated by both CRM1-dependent and -independent pathways. Together these results suggest that the regulation of NT-PGC-1αin muscle fibers may be very different from that of the full-length PGC-1α, which is exclusively nuclear.

The effects of PGC-1α on control of microvascular Po2 kinetics following onset of muscle contractions

2014 ◽  
Vol 117 (2) ◽  
pp. 163-170 ◽  
Author(s):  
Yutaka Kano ◽  
Shinji Miura ◽  
Hiroaki Eshima ◽  
Osamu Ezaki ◽  
David C. Poole
Keyword(s):  
Skeletal Muscle ◽  
Fiber Type ◽  
Endurance Performance ◽  
Oxidative Capacity ◽  
Muscle Contractions ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Phosphorescence Quenching ◽  
Slow Twitch ◽  
Fast Twitch

During contractions, regulation of microvascular oxygen partial pressure (Pmvo2), which drives blood-myocyte O2 flux, is a function of skeletal muscle fiber type and oxidative capacity and can be altered by exercise training. The kinetics of Pmvo2 during contractions in predominantly fast-twitch muscles evinces a more rapid fall to far lower levels compared with slow-twitch counterparts. Peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) improves endurance performance, in part, due to mitochondrial biogenesis, a fiber-type switch to oxidative fibers, and angiogenesis in skeletal muscle. We tested the hypothesis that improvement of exercise capacity by genetic overexpression of PGC-1α would be associated with an altered Pmvo2 kinetics profile of the fast-twitch (white) gastrocnemius during contractions toward that seen in slow-twitch muscles (i.e., slowed response kinetics and elevated steady-state Pmvo2). Phosphorescence quenching techniques were used to measure Pmvo2 at rest and during separate bouts of twitch (1 Hz) and tetanic (100 Hz) contractions in gastrocnemius muscles of mice with overexpression of PGC-1α and wild-type littermates (WT) mice under isoflurane anesthesia. Muscles of PGC-1α mice exhibited less fatigue than WT ( P < 0.01). However, except for the Pmvo2 response immediately following onset of contractions, WT and PGC-1α mice demonstrated similar Pmvo2 kinetics. Specifically, the time delay of the Pmvo2 response was shortened in PGC-1α mice compared with WT (1 Hz: WT, 6.6 ± 2.4 s; PGC-1α, 2.9 ± 0.8 s; 100 Hz: WT, 3.3 ± 1.1 s, PGC-1α, 0.9 ± 0.3 s, both P < 0.05). The ratio of muscle force to Pmvo2 was higher for the duration of tetanic contractions in PGC-1α mice. Slower dynamics and maintenance of higher Pmvo2 following muscle contractions is not obligatory for improved fatigue resistance in fast-twitch muscle of PGC-1α mice. Moreover, overexpression of PGC-1α may accelerate O2 utilization kinetics to a greater extent than O2 delivery kinetics.

scholarly journals IUGR Alters Postnatal Rat Skeletal Muscle Peroxisome Proliferator-Activated Receptor-γ Coactivator-1 Gene Expression in a Fiber Specific Manner

2003 ◽  
Vol 53 (6) ◽  
pp. 994-1000 ◽  
Author(s):  
Robert H Lane ◽  
Nicole K MacLennan ◽  
Monica J Daood ◽  
Jennifer L Hsu ◽  
Sara M Janke ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Peroxisome Proliferator ◽  
Rat Skeletal Muscle ◽  
Peroxisome Proliferator Activated Receptor ◽  
Specific Manner

scholarly journals Muscle-Specific PPARβ/δAgonism May Provide Synergistic Benefits with Life Style Modifications

PPAR Research ◽  
2007 ◽  
Vol 2007 ◽  
pp. 1-7
Author(s):  
Adnan Erol
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Fiber Type ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
Type I ◽  
Peroxisome Proliferator Activated Receptor ◽  
Targeted Expression

Peroxisome proliferator-activated receptorβ/δ(PPARβ/δ) has emerged as a powerful metabolic regulator in diverse tissues including fat, skeletal muscle, and the heart. It is now established that activation of PPARβ/δpromotes fatty acid oxidation in several tissues, such as skeletal muscle and adipose tissue. In muscle, PPARβ/δappears to act as a central regulator of fatty acid catabolism. PPARβ/δcontents are increased in muscle during physiological situations such as physical exercise or long-term fasting, characterized by increased fatty acid oxidation. Targeted expression of an activated form of PPARβ/δin skeletal muscle induces a switch to form increased numbers of type I muscle fibers resembling the fiber type transition by endurance training. Activation of PPARβ/δalso enhances mitochondrial capacity and fat oxidation in the skeletal muscle that resembles the effect of regular exercise. Therefore, it is hypothesized that muscle-specific PPARβ/δagonists could be a key strategy to support the poor cardiorespiratory fitness associated with metabolic disorders.

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