Coordination of mitochondrial biogenesis by PGC-1α in human skeletal muscle: A re-evaluation

Islam, Hashim; Edgett, Brittany A.; Gurd, Brendon J.

doi:10.1016/j.metabol.2017.11.001

Cited by 80 publications

(63 citation statements)

References 83 publications

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“…Based on temporal (Egan et al., ; Perry et al., ; Serpiello et al., ; Stepto et al., ) and correlational (Bonafiglia et al., ; Raue et al., ) relationships between acute changes in mRNA expression and chronic skeletal muscle adaptation, mRNA expression is frequently used as a primary outcome measure when determining the effectiveness of an acute exercise stimulus or when comparing exercise protocols that vary in intensity, duration, and/or volume (Granata et al., ; Islam et al., ; MacInnis et al., ; Miller et al., ). Further, as awareness of training response heterogeneity and interest in personalized exercise prescription has increased, changes in mRNA expression have also been examined at the individual level (Bamman et al., ; Osler et al., ; Teran‐Garcia et al., ; Timmons et al., ,b).…”

Section: Discussionmentioning

confidence: 99%

“…For example, increases in mRNA expression following acute exercise precede chronic increases in mitochondrial protein content (Egan, O'Connor, Zierath, & O'Gorman, ; Perry et al., ; Serpiello et al., ; Stepto et al., ) and correlate with training‐induced increases in muscle size, strength (Raue et al., ) and oxidative capacity (Bonafiglia et al., ). These finding have led to the assumption that larger increases in mRNA expression following acute exercise represent a greater activation of adaptive processes underlying skeletal muscle remodelling (Granata, Jamnick, & Bishop, ; Islam, Edgett, & Gurd, ; MacInnis et al., ; Miller, Konopka, & Hamilton, ). Thus, there is interest in examining factors that may explain inter‐individual variation in mRNA expression following acute exercise (Bajpeyi et al., ) and in comparing mRNA profiles between high and low responders for training‐induced changes in cardiorespiratory fitness (Timmons et al., ,b), blood glucose regulation (Osler et al., ; Teran‐Garcia, Rankinen, Koza, Rao, & Bouchard, ), and muscle hypertrophy (Bamman, Petrella, Kim, Mayhew, & Cross, ).…”

Section: Introductionmentioning

confidence: 99%

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Repeatability of exercise‐induced changes in mRNA expression and technical considerations for qPCR analysis in human skeletal muscle

Islam

Edgett

Bonafiglia

et al. 2019

Experimental Physiology

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New Findings What is the central question of this study?Are individual changes in exercise‐induced mRNA expression repeatable (i.e. representative of the true response to exercise rather than random error)? What is the main finding and its importance?Exercise‐induced changes in mRNA expression are not repeatable even under identical experimental conditions, thereby challenging the use of mRNA expression as a biomarker of adaptive potential and/or individual responsiveness to exercise. Abstract It remains unknown if (1) the observed change in mRNA expression reflects an individual's true response to exercise or random (technical and/or biological) error, and (2) the individual responsiveness to exercise is protocol‐specific. We examined the repeatability of skeletal muscle PGC‐1α, PDK4, NRF‐1, VEGF‐A, HSP72 and p53 mRNA expression following two identical endurance exercise (END) bouts (END‐1, END‐2; 30 min of cycling at 65% of peak work rate (WRpeak), n = 11) and inter‐individual variability in PGC‐1α and PDK4 mRNA expression following END and sprint interval training (SIT; 8 × 20 s cycling intervals at ∼170% WRpeak, n = 10) in active young males. The repeatability of key gene analysis steps (RNA extraction, reverse transcription, qPCR) and within‐sample fibre‐type distribution (n = 8) was also determined to examine potential sources of technical error in our analyses. Despite highly repeatable exercise bout characteristics (work rate, heart rate, blood lactate; ICC > 0.71; CV < 10%; r > 0.85, P < 0.01), gene analysis steps (ICC > 0.73; CV < 24%; r > 0.75, P < 0.01), and similar group‐level changes in mRNA expression, individual changes in PGC‐1α, PDK4, VEGF‐A and p53 mRNA expression were not repeatable (ICC < 0.22; CV > 20%; r < 0.21). Fibre‐type distribution in two portions of the same muscle biopsy was highly variable and not significantly related (ICC = 0.39; CV = 26%; r = 0.37, P = 0.37). Since individual changes in mRNA expression following identical exercise bouts were not repeatable, inferences regarding individual responsiveness to END or SIT were not made. Substantial random error exists in changes in mRNA expression following acute exercise, thereby challenging the use of mRNA expression for analysing individual responsiveness to exercise.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Repeatability of exercise‐induced changes in mRNA expression and technical considerations for qPCR analysis in human skeletal muscle

Islam

Edgett

Bonafiglia

et al. 2019

Experimental Physiology

Self Cite

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“…[1][2][3][4][5][6][7][8] While these responses are affected by the nature of the exercise (eg, the exercise intensity 2,9,10 ), there is evidence substrate availability is also a potent modulator of this response. [1][2][3][4][5][6][7][8] While these responses are affected by the nature of the exercise (eg, the exercise intensity 2,9,10 ), there is evidence substrate availability is also a potent modulator of this response.…”

Section: Introductionmentioning

confidence: 99%

Exercise twice‐a‐day potentiates markers of mitochondrial biogenesis in men

et al. 2019

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Endurance exercise begun with reduced muscle glycogen stores seems to potentiate skeletal muscle protein abundance and gene expression. However, it is unknown whether this greater signaling responses is due to performing two exercise sessions in close proximity—as a first exercise session is necessary to reduce the muscle glycogen stores. In the present study, we manipulated the recovery duration between a first muscle glycogen‐depleting exercise and a second exercise session, such that the second exercise session started with reduced muscle glycogen in both approaches but was performed either 2 or 15 hours after the first exercise session (so‐called “twice‐a‐day” and “once‐daily” approaches, respectively). We found that exercise twice‐a‐day increased the nuclear abundance of transcription factor EB (TFEB) and nuclear factor of activated T cells (NFAT) and potentiated the transcription of peroxisome proliferator‐activated receptor‐ɣ coactivator 1‐alpha (PGC‐1α), peroxisome proliferator‐activated receptor‐alpha (PPARα), and peroxisome proliferator‐activated receptor beta/delta (PPARβ/δ) genes, in comparison with the once‐daily exercise. These results suggest that part of the elevated molecular signaling reported with previous “train‐low” approaches might be attributed to performing two exercise sessions in close proximity. The twice‐a‐day approach might be an effective strategy to induce adaptations related to mitochondrial biogenesis and fat oxidation.

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“…vastus lateralis (see review (Islam et al. )); aerobic training increases baseline expression of the TFAM protein (Norrbom et al. ; Bori et al.…”

Section: Discussionmentioning

confidence: 99%

“…PGC-1a coactivator and its partners nuclear respiratory factors 1 and 2 play an important role in regulating TFAM expression (Scarpulla 2008). More than ten studies show that aerobic exercise increases expression of TFAM mRNA in human m. vastus lateralis (see review (Islam et al 2018)); aerobic training increases baseline expression of the TFAM protein (Norrbom et al 2010;Bori et al 2012;Granata et al 2016). Here, we show that training increased baseline expression of this protein without increasing basal expression of the TFAM gene, a finding consistent with that of previous work (Norrbom et al 2010).…”

Section: Baseline Levels Of Transcriptional Regulatorsmentioning

confidence: 99%

Effect of aerobic training on baseline expression of signaling and respiratory proteins in human skeletal muscle

et al. 2018

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Most studies examining the molecular mechanisms underlying adaptation of human skeletal muscles to aerobic exercise focused on the response to acute exercise. Here, we examined the effect of a 2‐month aerobic training program on baseline parameters in human muscle. Ten untrained males performed a one‐legged knee extension exercise for 1 h with the same relative intensity before and after a 2‐month aerobic training program. Biopsy samples were taken from vastus lateralis muscle at rest before and after the 2 month training program (baseline samples). Additionally, biopsy samples were taken from the exercised leg 1 and 4 h after the one‐legged continuous knee extension exercise. Aerobic training decreases baseline phosphorylation of FOXO1Ser256, increases that of CaMKIIT hr286, CREB1Ser133, increases baseline expression of mitochondrial proteins in respiratory complexes I–V, and some regulators of mitochondrial biogenesis (TFAM, NR4A3, and CRTC2). An increase in the baseline content of these proteins was not associated with a change in baseline expression of their genes. The increase in the baseline content of regulators of mitochondrial biogenesis (TFAM and NR4A3) was associated with a transient increase in transcription after acute exercise. Contrariwise, the increase in the baseline content of respiratory proteins does not seem to be regulated at the transcriptional level; rather, it is associated with other mechanisms. Adaptation of human skeletal muscle to regular aerobic exercise is associated not only with transient molecular responses to exercise, but also with changes in baseline phosphorylation and expression of regulatory proteins.

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Coordination of mitochondrial biogenesis by PGC-1α in human skeletal muscle: A re-evaluation

Cited by 80 publications

References 83 publications

Repeatability of exercise‐induced changes in mRNA expression and technical considerations for qPCR analysis in human skeletal muscle

Repeatability of exercise‐induced changes in mRNA expression and technical considerations for qPCR analysis in human skeletal muscle

Exercise twice‐a‐day potentiates markers of mitochondrial biogenesis in men

Effect of aerobic training on baseline expression of signaling and respiratory proteins in human skeletal muscle

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