scholarly journals Role of PGC-1α during acute exercise-induced autophagy and mitophagy in skeletal muscle

2015 ◽  
Vol 308 (9) ◽  
pp. C710-C719 ◽  
Author(s):  
Anna Vainshtein ◽  
Liam D. Tryon ◽  
Marion Pauly ◽  
David A. Hood
Keyword(s):  
Skeletal Muscle ◽  
Acute Exercise ◽  
Transmembrane Protein ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Lipid Trafficking ◽  
Mitochondrial Transcription Factor ◽  
Energy Demands ◽  
Niemann Pick ◽  
Exercise Induced

Regular exercise leads to systemic metabolic benefits, which require remodeling of energy resources in skeletal muscle. During acute exercise, the increase in energy demands initiate mitochondrial biogenesis, orchestrated by the transcriptional coactivator peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α). Much less is known about the degradation of mitochondria following exercise, although new evidence implicates a cellular recycling mechanism, autophagy/mitophagy, in exercise-induced adaptations. How mitophagy is activated and what role PGC-1α plays in this process during exercise have yet to be evaluated. Thus we investigated autophagy/mitophagy in muscle immediately following an acute bout of exercise or 90 min following exercise in wild-type (WT) and PGC-1α knockout (KO) animals. Deletion of PGC-1α resulted in a 40% decrease in mitochondrial content, as well as a 25% decline in running performance, which was accompanied by severe acidosis in KO animals, indicating metabolic distress. Exercise induced significant increases in gene transcripts of various mitochondrial (e.g., cytochrome oxidase subunit IV and mitochondrial transcription factor A) and autophagy-related (e.g., p62 and light chain 3) genes in WT, but not KO, animals. Exercise also resulted in enhanced targeting of mitochondria for mitophagy, as well as increased autophagy and mitophagy flux, in WT animals. This effect was attenuated in the absence of PGC-1α. We also identified Niemann-Pick C1, a transmembrane protein involved in lysosomal lipid trafficking, as a target of PGC-1α that is induced with exercise. These results suggest that mitochondrial turnover is increased following exercise and that this effect is at least in part coordinated by PGC-1α. Anna Vainshtein received the AJP-Cell 2015 Paper of the Year award. Listen to a podcast with Anna Vainshtein and coauthor David A. Hood at http://ajpcell.podbean.com/e/ajp-cell-paper-of-the-year-2015-award-podcast/ .

Effect of nitric oxide synthase inhibition on mitochondrial biogenesis in rat skeletal muscle

2007 ◽  
Vol 102 (1) ◽  
pp. 314-320 ◽  
Author(s):  
G. D. Wadley ◽  
G. K. McConell
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Mitochondrial Biogenesis ◽  
Acute Exercise ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Peroxisome Proliferator Activated Receptor ◽  
Exercise Induced ◽  
Edl Muscle ◽  
Oxide Synthase

The purpose of this study was to determine whether nitric oxide synthase (NOS) inhibition decreased basal and exercise-induced skeletal muscle mitochondrial biogenesis. Male Sprague-Dawley rats were assigned to one of four treatment groups: NOS inhibitor NG-nitro-l-arginine methyl ester (l-NAME, ingested for 2 days in drinking water, 1 mg/ml) followed by acute exercise, no l-NAME ingestion and acute exercise, rest plus l-NAME, and rest without l-NAME. The exercised rats ran on a treadmill for 53 ± 2 min and were then killed 4 h later. NOS inhibition significantly ( P < 0.05; main effect) decreased basal peroxisome proliferator-activated receptor-γ coactivator 1β (PGC-1β) mRNA levels and tended ( P = 0.08) to decrease mtTFA mRNA levels in the soleus, but not the extensor digitorum longus (EDL) muscle. This coincided with significantly reduced basal levels of cytochrome c oxidase (COX) I and COX IV mRNA, COX IV protein and COX enzyme activity following NOS inhibition in the soleus, but not the EDL muscle. NOS inhibition had no effect on citrate synthase or β-hydroxyacyl CoA dehydrogenase activity, or cytochrome c protein abundance in the soleus or EDL. NOS inhibition did not reduce the exercise-induced increase in peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) mRNA in the soleus or EDL. In conclusion, inhibition of NOS appears to decrease some aspects of the mitochondrial respiratory chain in the soleus under basal conditions, but does not attenuate exercise-induced mitochondrial biogenesis in the soleus or in the EDL.

scholarly journals The Importance of Fatty Acids as Nutrients during Post-Exercise Recovery

Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 280 ◽  
Author(s):  
Anne-Marie Lundsgaard ◽  
Andreas M. Fritzen ◽  
Bente Kiens
Keyword(s):  
Skeletal Muscle ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Whole Body ◽  
Tissue Blood Flow ◽  
Peroxisome Proliferator ◽  
Early Recovery ◽  
Peroxisome Proliferator Activated Receptor ◽  
Post Exercise ◽  
Exercise Induced

It is well recognized that whole-body fatty acid (FA) oxidation remains increased for several hours following aerobic endurance exercise, even despite carbohydrate intake. However, the mechanisms involved herein have hitherto not been subject to a thorough evaluation. In immediate and early recovery (0–4 h), plasma FA availability is high, which seems mainly to be a result of hormonal factors and increased adipose tissue blood flow. The increased circulating availability of adipose-derived FA, coupled with FA from lipoprotein lipase (LPL)-derived very-low density lipoprotein (VLDL)-triacylglycerol (TG) hydrolysis in skeletal muscle capillaries and hydrolysis of TG within the muscle together act as substrates for the increased mitochondrial FA oxidation post-exercise. Within the skeletal muscle cells, increased reliance on FA oxidation likely results from enhanced FA uptake into the mitochondria through the carnitine palmitoyltransferase (CPT) 1 reaction, and concomitant AMP-activated protein kinase (AMPK)-mediated pyruvate dehydrogenase (PDH) inhibition of glucose oxidation. Together this allows glucose taken up by the skeletal muscles to be directed towards the resynthesis of glycogen. Besides being oxidized, FAs also seem to be crucial signaling molecules for peroxisome proliferator-activated receptor (PPAR) signaling post-exercise, and thus for induction of the exercise-induced FA oxidative gene adaptation program in skeletal muscle following exercise. Collectively, a high FA turnover in recovery seems essential to regain whole-body substrate homeostasis.

scholarly journals Adult expression of PGC-1α and -1β in skeletal muscle is not required for endurance exercise-induced enhancement of exercise capacity

2016 ◽  
Vol 311 (6) ◽  
pp. E928-E938 ◽  
Author(s):  
Christopher Ballmann ◽  
Yawen Tang ◽  
Zachary Bush ◽  
Glenn C. Rowe
Keyword(s):  
Skeletal Muscle ◽  
Exercise Performance ◽  
Whole Body ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Adult Skeletal Muscle ◽  
Training Response ◽  
Exercise Induced ◽  
Transport Complex ◽  
Specific Deletion

Exercise has been shown to be the best intervention in the treatment of many diseases. Many of the benefits of exercise are mediated by adaptions induced in skeletal muscle. The peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family of transcriptional coactivators has emerged as being key mediators of the exercise response and is considered to be essential for many of the adaptions seen in skeletal muscle. However, the contribution of the PGC-1s in skeletal muscle has been evaluated by the use of either whole body or congenital skeletal muscle-specific deletion. In these models, PGC-1s were never present, thereby opening the possibility to developmental compensation. Therefore, we generated an inducible muscle-specific deletion of PGC-1α and -1β (iMyo-PGC-1DKO), in which both PGC-1α and -β can be deleted specifically in adult skeletal muscle. These iMyo-PGC-1DKO animals were used to assess the role of both PGC-1α and -1β in adult skeletal muscle and their contribution to the exercise training response. Untrained iMyo-PGC-1DKO animals exhibited a time-dependent decrease in exercise performance 8 wk postdeletion, similar to what was observed in the congenital muscle-specific PGC-1DKOs. However, after 4 wk of voluntary training, the iMyo-PGC-1DKOs exhibited an increase in exercise performance with a similar adaptive response compared with control animals. This increase was associated with an increase in electron transport complex (ETC) expression and activity in the absence of PGC-1α and -1β expression. Taken together these data suggest that PGC-1α and -1β expression are not required for training-induced exercise performance, highlighting the contribution of PGC-1-independent mechanisms.

scholarly journals Metabolic regulation of exercise-induced angiogenesis

2019 ◽  
Vol 1 (1) ◽  
pp. H1-H8 ◽  
Author(s):  
Tatiane Gorski ◽  
Katrien De Bock
Keyword(s):  
Skeletal Muscle ◽  
Transcriptional Activation ◽  
Metabolic Regulation ◽  
Molecular Mechanisms ◽  
Metabolic Reprogramming ◽  
Sirtuin 1 ◽  
Peroxisome Proliferator ◽  
Valuable Insight ◽  
Peroxisome Proliferator Activated Receptor ◽  
Exercise Induced

Skeletal muscle relies on an ingenious network of blood vessels, which ensures optimal oxygen and nutrient supply. An increase in muscle vascularization is an early adaptive event to exercise training, but the cellular and molecular mechanisms underlying exercise-induced blood vessel formation are not completely clear. In this review, we provide a concise overview on how exercise-induced alterations in muscle metabolism can evoke metabolic changes in endothelial cells (ECs) that drive muscle angiogenesis. In skeletal muscle, angiogenesis can occur via sprouting and splitting angiogenesis and is dependent on vascular endothelial growth factor (VEGF) signaling. In the resting muscle, VEGF levels are controlled by the estrogen-related receptor γ (ERRγ). Upon exercise, the transcriptional coactivator peroxisome-proliferator-activated receptor-γ coactivator-1α (PGC1α) orchestrates several adaptations to endurance exercise within muscle fibers and simultaneously promotes transcriptional activation of Vegf expression and increased muscle capillary density. While ECs are highly glycolytic and change their metabolism during sprouting angiogenesis in development and disease, a similar role for EC metabolism in exercise-induced angiogenesis in skeletal muscle remains to be elucidated. Nonetheless, recent studies have illustrated the importance of endothelial hydrogen sulfide and sirtuin 1 (SIRT1) activity for exercise-induced angiogenesis, suggesting that EC metabolic reprogramming may be fundamental in this process. We hypothesize that the exercise-induced angiogenic response can also be modulated by metabolic crosstalk between muscle and the endothelium. Defining the underlying molecular mechanisms responsible for skeletal muscle angiogenesis in response to exercise will yield valuable insight into metabolic regulation as well as the determinants of exercise performance.

scholarly journals An Increase in Murine Skeletal Muscle Peroxisome Proliferator-Activated Receptor-γ Coactivator-1α (PGC-1α) mRNA in Response to Exercise Is Mediated by β-Adrenergic Receptor Activation

Endocrinology ◽  
2007 ◽  
Vol 148 (7) ◽  
pp. 3441-3448 ◽  
Author(s):  
Shinji Miura ◽  
Kentaro Kawanaka ◽  
Yuko Kai ◽  
Mayumi Tamura ◽  
Masahide Goto ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Mrna Expression ◽  
Adrenergic Receptor ◽  
Ex Vivo ◽  
Specific Inhibitor ◽  
Receptor Activation ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Brown Adipose ◽  
Exercise Induced

A single bout of exercise increases expression of peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α mRNA, which may promote mitochondrial biogenesis in skeletal muscle. In brown adipose tissue, cold exposure up-regulates PGC-1α expression via adrenergic receptor (AR) activation. Because exercise also activates the sympathetic nervous system, we examined whether exercise-induced increase in PGC-1α mRNA expression in skeletal muscle was mediated via AR activation. In C57BL/6J mice, injection of the β2-AR agonist clenbuterol, but not α-, β1-, or β3-AR agonists, increased PGC-1α mRNA expression more than 30-fold in skeletal muscle. The clenbuterol-induced increase in PGC-1α mRNA expression in mice was inhibited by pretreatment with the β-AR antagonist propranolol. In ex vivo experiments, direct exposure of rat epitrochlearis to β2-AR agonist, but not α-, β1-, and β3-AR agonist, led to an increase in levels of PGC-1α mRNA. Injection of β2-AR agonist did not increase PGC-1α mRNA expression in β1-, β2-, and β3-AR knockout mice (β-less mice). PGC-1α mRNA in gastrocnemius was increased 3.5-fold in response to running on a treadmill for 45 min. The exercise-induced increase in PGC-1α mRNA was inhibited by approximately 70% by propranolol or the β2-AR-specific inhibitor ICI 118,551. The exercise-induced increase in PGC-1α mRNA in β-less mice was also 36% lower than that in wild-type mice. These data indicate that up-regulation of PGC-1α expression in skeletal muscle by exercise is mediated, at least in part, by β-ARs activation. Among ARs, β2-AR may mediate an increase in PGC-1α by exercise.

Effects of acute bouts of running and swimming exercise on PGC-1α protein expression in rat epitrochlearis and soleus muscle

2004 ◽  
Vol 286 (2) ◽  
pp. E208-E216 ◽  
Author(s):  
Shin Terada ◽  
Izumi Tabata
Keyword(s):  
Skeletal Muscle ◽  
Protein Expression ◽  
Skeletal Muscles ◽  
Peroxisome Proliferator ◽  
Ampk Activation ◽  
Peroxisome Proliferator Activated Receptor ◽  
Number Of Factors ◽  
Exercise Induced ◽  
Low Intensity Exercise

The purpose of this study was to elucidate the mechanisms underlying low-intensity exercise-induced peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) protein expression in rat skeletal muscles. Rats (5–6 wk old) swam without a load and ran on the treadmill at a speed of 13 m/min, respectively, in two 3-h sessions separated by 45 min of rest. PGC-1α content in epitrochlearis muscle (EPI) was increased by 75 and 95%, immediately and 6 h after swimming, respectively, with no increase in PGC-1α content in the soleus (SOL). After running, PGC-1α content in EPI was unchanged, whereas a 107% increase in PGC-1α content was observed in SOL 6 h after running. Furthermore, in EPI and SOL as well as other muscles (triceps, plantaris, red and white gastrocnemius), PGC-1α expression was enhanced concomitant with reduced glycogen postexercise, suggesting that expression of PGC-1α occurs in skeletal muscle recruited during exercise. PGC-1α content in EPI was increased after 18-h in vitro incubation with 0.5 mM 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) and 4 mM caffeine. However, AICAR incubation did not affect PGC-1α content in the SOL, whereas caffeine incubation increased it. These results suggest that exercise-induced PGC-1α expression in skeletal muscle may be mediated by at least two exercise-induced signaling factors: AMPK activation and Ca2+ elevation. The number of factors involved (both AMPK and Ca2+, or Ca2+ only) in exercise-induced PGC-1α expression may differ among muscles.

scholarly journals A systematic upregulation of nuclear and mitochondrial genes is not present in the initial postexercise recovery period in human skeletal muscle

2017 ◽  
Vol 42 (6) ◽  
pp. 571-578 ◽  
Author(s):  
Trisha D. Scribbans ◽  
Brittany A. Edgett ◽  
Jacob T. Bonafiglia ◽  
Brittany L. Baechler ◽  
Joe Quadrilatero ◽  
...  
Keyword(s):  
Oxygen Uptake ◽  
Messenger Rna ◽  
Acute Exercise ◽  
Recovery Period ◽  
Exercise Bout ◽  
Peak Oxygen Uptake ◽  
Peroxisome Proliferator ◽  
Glycogen Depletion ◽  
Peroxisome Proliferator Activated Receptor ◽  
Exercise Induced

The purpose of the current investigation was to determine if an exercise-mediated upregulation of nuclear and mitochondrial-encoded genes targeted by the transcriptional co-activator peroxisome-proliferator-activated receptor gamma co-activator-1 alpha (PGC-1α) occurs in a systematic manner following different exercise intensities in humans. Ten recreationally active males (age: 23 ± 3 years; peak oxygen uptake: 41.8 ± 6.6 mL·kg−1·min−1) completed 2 acute bouts of work-matched interval exercise at ∼73% (low; LO) and ∼100% (high; HI) of work rate at peak oxygen uptake in a randomized crossover design. Muscle biopsies were taken before, immediately after, and 3 h into recovery following each exercise bout. A main effect of time (p < 0.05) was observed for glycogen depletion. PGC-1α messenger RNA (mRNA) increased following both conditions and was significantly (p < 0.05) higher following HI compared with LO (PGC-1α, LO: +442% vs. HI: +845%). PDK4 mRNA increased following LO whereas PPARα, NRF1, and CS increased following HI. However, a systematic upregulation of nuclear and mitochondrial-encoded genes was not present as TFAM, COXIV, COXI, COXII, ND1, and ND4 mRNA were unchanged. However, changes in COXI, COXII, ND1 and ND4 mRNA were positively correlated following LO and COXI, ND1, and ND4 were positively correlated following HI, which suggests mitochondrial-encoded gene expression was coordinated. PGC-1α and ND4 mRNA, as well as PGC-1α mRNA and the change in muscle glycogen, were positively correlated in response to LO. The lack of observed systematic upregulation of nuclear- and mitochondrial-encoded genes suggests that exercise-induced upregulation of PGC-1α targets are differentially regulated during the initial hours following acute exercise in humans.

scholarly journals Thyroid hormone activation by type 2 deiodinase mediates exercise-induced peroxisome proliferator-activated receptor-γ coactivator-1α expression in skeletal muscle

2016 ◽  
Vol 594 (18) ◽  
pp. 5255-5269 ◽  
Author(s):  
Barbara M. L. C. Bocco ◽  
Ruy A. N. Louzada ◽  
Diego H. S. Silvestre ◽  
Maria C. S. Santos ◽  
Elena Anne-Palmer ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Thyroid Hormone ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Exercise Induced

scholarly journals p53 is necessary for the adaptive changes in cellular milieu subsequent to an acute bout of endurance exercise

2014 ◽  
Vol 306 (3) ◽  
pp. C241-C249 ◽  
Author(s):  
Ayesha Saleem ◽  
Heather N. Carter ◽  
David A. Hood
Keyword(s):  
Endurance Exercise ◽  
Mitochondrial Biogenesis ◽  
Messenger Rna ◽  
Acute Exercise ◽  
Peroxisome Proliferator ◽  
Subsequent Increase ◽  
Peroxisome Proliferator Activated Receptor ◽  
Acute Bout ◽  
Downstream Signaling ◽  
Exercise Induced

An acute bout of exercise activates downstream signaling cascades that ultimately result in mitochondrial biogenesis. In addition to inducing mitochondrial synthesis, exercise triggers the removal of damaged cellular material via autophagy and of dysfunctional mitochondria through mitophagy. Here, we investigated the necessity of p53 to the changes that transpire within the muscle upon an imposed metabolic and physiological challenge, such as a bout of endurance exercise. We randomly assigned wild-type (WT) and p53 knockout (KO) mice to control, acute exercise (AE; 90 min at 15 m/min), and AE + 3 h recovery (AER) groups and measured downstream alterations in markers of mitochondrial biogenesis, autophagy, and mitophagy. In the absence of p53, activation of p38 MAPK upon exercise was abolished, whereas CaMKII and AMP-activated protein kinase only displayed an attenuated enhancement in the AER group compared with WT mice. The translocation of peroxisome proliferator-activated receptor-γ coactivator-1 α to the nucleus was diminished and only observed in the AER group, and the subsequent increase in messenger RNA transcripts related to mitochondrial biogenesis with exercise and recovery was absent in the p53 KO animals. Whole-muscle autophagic and lysosomal markers did not respond to exercise, irrespective of the genotype of the exercised mice, with the exception of increased ubiquitination observed in KO mice with exercise. Markers of mitophagy were elevated in response to AE and AER conditions in both WT and p53 KO runners. The data suggest that p53 is important for the exercise-induced activation of mitochondrial synthesis and is integral in regulating autophagy during control conditions but not in response to exercise.

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