Acute endurance exercise increases the nuclear abundance of PGC-1α in trained human skeletal muscle

2010 ◽  
Vol 298 (4) ◽  
pp. R912-R917 ◽  
Author(s):  
Jonathan P. Little ◽  
Adeel Safdar ◽  
Naomi Cermak ◽  
Mark A. Tarnopolsky ◽  
Martin J. Gibala
Keyword(s):  
Skeletal Muscle ◽  
P38 Mapk ◽  
Endurance Exercise ◽  
Human Skeletal Muscle ◽  
Muscle Activation ◽  
Mitochondrial Gene ◽  
Ampk Activation ◽  
Acute Bout ◽  
Nuclear Abundance ◽  
Whole Muscle

Peroxisome proliferator-activated receptor gamma coactivator (PGC-1α) is a transcriptional coactivator that plays a key role in coordinating mitochondrial biogenesis. Recent evidence has linked p38 MAPK and AMPK with activation of PGC-1α. It was recently shown in rodent skeletal muscle that acute endurance exercise causes a shift in the subcellular localization of PGC-1α from the cytosol to the nucleus, allowing PGC-1α to coactivate transcription factors and increase mitochondrial gene expression, but human data are limited and equivocal in this regard. Our purpose was to examine p38 MAPK and AMPK activation, and PGC-1α protein content in whole muscle, cytosolic, and nuclear fractions of human skeletal muscle following an acute bout of endurance exercise. Eight trained men (29 ± 3 yr; V̇o2peak = 55 ± 2 ml·kg−1·min−1) cycled for 90 min at ∼65% of V̇o2peak and needle biopsy samples (vastus lateralis) were obtained before and immediately after exercise. At rest, the majority of PGC-1α was detected in cytosolic compared with the nuclear fractions. In response to exercise, nuclear PGC-1α protein increased by 54% ( P < 0.05), yet whole muscle PGC-1α protein was unchanged compared with rest. Whole muscle and cytosolic p38 MAPK phosphorylation increased several-fold immediately after exercise compared with rest ( P < 0.05). Acetyl CoA carboxylase (ACC) phosphorylation, a marker of AMPK activation, was increased by ∼5-fold in cytosolic fractions following exercise ( P < 0.05). These data provide evidence that, in human skeletal muscle, activation of cytosolic p38 MAPK and AMPK may be potential signals that lead to increased nuclear abundance and activation of PGC-1α in response to an acute bout of endurance exercise.

An acute bout of high-intensity interval training increases the nuclear abundance of PGC-1α and activates mitochondrial biogenesis in human skeletal muscle

2011 ◽  
Vol 300 (6) ◽  
pp. R1303-R1310 ◽  
Author(s):  
Jonathan P. Little ◽  
Adeel Safdar ◽  
David Bishop ◽  
Mark A. Tarnopolsky ◽  
Martin J. Gibala
Keyword(s):  
Skeletal Muscle ◽  
Mitochondrial Biogenesis ◽  
High Intensity ◽  
Human Skeletal Muscle ◽  
Interval Training ◽  
High Intensity Interval Training ◽  
Acute Bout ◽  
Nuclear Abundance ◽  
Low Volume ◽  
High Intensity Interval

Low-volume, high-intensity interval training (HIT) increases skeletal muscle mitochondrial capacity, yet little is known regarding potential mechanisms promoting this adaptive response. Our purpose was to examine molecular processes involved in mitochondrial biogenesis in human skeletal muscle in response to an acute bout of HIT. Eight healthy men performed 4 × 30-s bursts of all-out maximal intensity cycling interspersed with 4 min of rest. Muscle biopsy samples (vastus lateralis) were obtained immediately before and after exercise, and after 3 and 24 h of recovery. At rest, the majority of peroxisome proliferator-activated receptor γ coactivator (PGC)-1α, a master regulator of mitochondrial biogenesis, was detected in cytosolic fractions. Exercise activated p38 MAPK and AMPK in the cytosol. Nuclear PGC-1α protein increased 3 h into recovery from exercise, a time point that coincided with increased mRNA expression of mitochondrial genes. This was followed by an increase in mitochondrial protein content and enzyme activity after 24 h of recovery. These findings support the hypothesis that an acute bout of low-volume HIT activates mitochondrial biogenesis through a mechanism involving increased nuclear abundance of PGC-1α.

Skeletal muscle adaptations to exercise are not influenced by metformin treatment in humans: secondary analyses of two randomised, clinical trials.

2021 ◽  
Author(s):  
Nanna Skytt Pilmark ◽  
Laura Oberholzer ◽  
Jens Frey Halling ◽  
Jonas M. Kristensen ◽  
Christina Pedersen Bønding ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Exercise Training ◽  
Human Skeletal Muscle ◽  
Acute Exercise ◽  
Metformin Treatment ◽  
Ampk Activation ◽  
Double Blind ◽  
Parallel Group ◽  
Exercise Induced

Metformin and exercise both improve glycemic control, but in vitro studies have indicated that an interaction between metformin and exercise occurs in skeletal muscle, suggesting a blunting effect of metformin on exercise training adaptations. Two studies (a double-blind, parallel-group, randomized clinical trial conducted in 29 glucose-intolerant individuals and a double-blind, cross-over trial conducted in 15 healthy lean males) were included in this paper. In both studies, the effect of acute exercise +/- metformin treatment on different skeletal muscle variables, previously suggested to be involved in a pharmaco-physiological interaction between metformin and exercise, was assessed. Furthermore, in the parallel-group trial, the effect of 12 weeks of exercise training was assessed. Skeletal muscle biopsies were obtained before and after acute exercise and 12 weeks of exercise training, and mitochondrial respiration, oxidative stress and AMPK activation was determined. Metformin did not significantly affect the effects of acute exercise or exercise training on mitochondrial respiration, oxidative stress or AMPK activation, indicating that the response to acute exercise and exercise training adaptations in skeletal muscle is not affected by metformin treatment. Further studies are needed to investigate whether an interaction between metformin and exercise is present in other tissues, e.g. the gut. Trial registration: ClinicalTrials.gov (NCT03316690 and NCT02951260). Novelty bullets • Metformin does not affect exercise-induced alterations in mitochondrial respiratory capacity in human skeletal muscle • Metformin does not affect exercise-induced alterations in systemic levels of oxidative stress nor emission of reactive oxygen species from human skeletal muscle • Metformin does not affect exercise-induced AMPK activation in human skeletal muscle

scholarly journals Improved assessment of the global transcriptional response to endurance exercise in human skeletal muscle

2010 ◽  
Vol 24 (S1) ◽  
Author(s):  
Justin Crane ◽  
Daniel Ogborn ◽  
Arkan Abadi ◽  
Simon Melov ◽  
Alan Hubbard ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Endurance Exercise ◽  
Human Skeletal Muscle ◽  
Transcriptional Response

scholarly journals Regulation of miRNAs in human skeletal muscle following acute endurance exercise and short-term endurance training

2013 ◽  
Vol 591 (18) ◽  
pp. 4637-4653 ◽  
Author(s):  
Aaron P. Russell ◽  
Severine Lamon ◽  
Hanneke Boon ◽  
Shogo Wada ◽  
Isabelle Güller ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Endurance Training ◽  
Endurance Exercise ◽  
Human Skeletal Muscle ◽  
Short Term

scholarly journals Striated muscle activator of Rho signalling (STARS) is a PGC-1α/oestrogen-related receptor-α target gene and is upregulated in human skeletal muscle after endurance exercise

2011 ◽  
Vol 589 (8) ◽  
pp. 2027-2039 ◽  
Author(s):  
Marita A. Wallace ◽  
M. Benjamin Hock ◽  
Bethany C. Hazen ◽  
Anastasia Kralli ◽  
Rod J. Snow ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Endurance Exercise ◽  
Human Skeletal Muscle ◽  
Target Gene ◽  
Striated Muscle

scholarly journals Muscle specific microRNAs are regulated by endurance exercise in human skeletal muscle

2010 ◽  
Vol 588 (20) ◽  
pp. 4029-4037 ◽  
Author(s):  
Søren Nielsen ◽  
Camilla Scheele ◽  
Christina Yfanti ◽  
Thorbjörn Åkerström ◽  
Anders R. Nielsen ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Endurance Exercise ◽  
Human Skeletal Muscle

scholarly journals Repeated-ischaemic exercise enhances mitochondrial and ion transport gene adaptations in human skeletal muscle – Role of muscle redox state and AMPK

2017 ◽  
Author(s):  
Danny Christiansen ◽  
Robyn M. Murphy ◽  
Jens Bangsbo ◽  
Christos G. Stathis ◽  
David J. Bishop
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Human Skeletal Muscle ◽  
Exercise Session ◽  
Type I ◽  
Ampk Activation ◽  
Stress Markers ◽  
Gene Response ◽  
Mrna Content ◽  
Muscle Gene

AbstractThis study assessed the effect of repeated-ischaemic exercise on the mRNA content of PGC-1α (total, 1α1, and 1α4) and Na+,K+-ATPase (NKA; α1-3, β1-3, and FXYD1) isoforms in human skeletal muscle, and studied some of the potential molecular mechanisms involved. Eight trained men (26 ± 5 y and 57.4 ± 6.3 mL·kg-1·min-1) completed three interval running sessions with (ISC) or without ischaemia (CON), or in hypoxia (HYP, ~3250 m), in a randomised, crossover fashion separated by 1 week. A muscle sample was collected from the dominant leg before (Pre) and after exercise (+0h, +3h) in all sessions to measure the mRNA content of PGC-1α and NKA isoforms, oxidative stress markers (i.e. catalase and HSP70 mRNA), muscle lactate, and phosphorylation of AMPK, ACC, CaMKII, and PLB protein in type I and II fibres. Muscle hypoxia (i.e. deoxygenated haemoglobin) was matched between ISC and HYP, which was higher than in CON (~90% vs. ~70%; p< 0.05). The levels of PGC-1α total, -1α1, −1α4, and FXYD1 mRNA increased in ISC only (p< 0.05). These changes were associated with increases in oxidative stress markers and higher p-ACCSer221/ACC in type I fibres, but were unrelated to muscle hypoxia, lactate, and CaMKII and PLB phosphorylation. These findings highlight that repeated-ischaemic exercise augments the skeletal muscle gene response related to mitochondrial biogenesis and ion transport in trained men. This effect seems attributable, in part, to increased oxidative stress and AMPK activation, whereas it appears unrelated to altered CaMKII signalling, and the muscle hypoxia and lactate accumulation induced by ischaemia.Summary in key pointsWe investigated if ischaemia would augment the exercise-induced mRNA response of PGC-1α and Na+,K+-ATPase (NKA) isoforms (α1-3, β1-3, and FXYD1), and examined whether this effect could be related to oxidative stress and fibre type-dependent AMPK and CaMKII signalling in the skeletal muscle of trained men.Repeated-ischaemic exercise increased the mRNA content of PGC-1α total, −1α1, and-1α4, and of the NKA regulatory subunit FXYD1, whereas exercise in systemic hypoxia or alone was without effect on these genes.These responses to ischaemia were complemented by increased oxidative stress (as assessed by catalase and HSP70 mRNA) and ACC phosphorylation (an indicator of AMPK activation) in type I fibres. However, they were unrelated to CaMKII signalling, muscle hypoxia, and lactate accumulation.Thus, repeated ischaemic exercise augments the muscle gene response associated with mitochondrial biogenesis and ion homeostasis in trained men. This effect seems partly attributable to promoted oxidative stress and AMPK activation.AbbreviationsACCAcetyl-CoA carboxylaseAMPK5’ AMP-activated protein kinase subunitβ2Mβ2 microglobulinCaMKIICa2+-calmodulin-dependent protein kinase isoform IICONcontrol sessionCTcycle thresholdCVcoefficient of variationFXYD1phospholemman isoform 1GAPDHglyceraldehyde 3-phosphate dehydrogenaseGXTgraded exercise testHHbdeoxygenated haemoglobinHSP70heat-shock protein 70HYPrepeated-hypoxic exercise sessionISCrepeated-ischaemic exercise sessionK+potassium ionLTlactate thresholdMHCmyosin heavy chainNa+sodium ionNIRSnear-infrared spectroscopyNKANa+, K+-ATPaseOXPHOSoxidative phosphorylationPGC-1αperoxisome proliferator-activated receptor-gamma coactivator 1 alphaPLBphospholambanROSreactive oxygen speciesSDSsodium dodecyl sulphateTBPTATA-binding proteinVO2maxmaximum oxygen uptake

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