Transcriptional control, but not subcellular location, of PGC-1α is altered following exercise in a hot environment

Heesch, Matthew; Shute, Robert; Kreiling, Jodi L.; Slivka, Dustin

doi:10.1152/japplphysiol.01065.2015

Cited by 24 publications

(34 citation statements)

References 49 publications

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“…It was concluded that exercise intensity, rather than exercise volume, may be an important factor affecting exerciseinduced changes in nuclear PGC-1α protein content. These suggestions are confirmed when pooling results from the available literature, which indicates that a single session of MICE at ~55 to 75% of Ẇmax does not induce a large increase (~1 to 1.5-fold) in nuclear PGC-1α protein content [14,86,[91][92][93], whereas all-out SIE is associated with larger increases (~1.7 to 2.3fold), despite much lower exercise volumes [14,15]. Further research is required to confirm these hypotheses and to characterize the effects of exercise volume on PGC-1α subcellular localization.…”

Section: Exercise-induced Changes In Nuclear Pgc-1α Protein Contentsupporting

confidence: 57%

“…Research in human skeletal muscle demonstrates the exercise-induced accumulation of PGC-1α protein in the nucleus takes place before increases in the cytosol [14,15,86,91]. Studies have attributed this increase to increased PGC-1α protein stability mediated by p38 MAPK and/or AMPK [14,15,86], and/or greater nuclear import from, or decreased nuclear export to, the cytosol of existing PGC-1α protein [15,86,91]. Regardless, the early accumulation of PGC-1α protein in the nucleus has been linked with an increase in the activity of existing PGC-1α protein, an event that may mediate the initial phase of exercise-induced mitochondrial biogenesis [14,15,89].…”

Section: Exercise-induced Changes In Nuclear Pgc-1α Protein Contentmentioning

confidence: 99%

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Principles of Exercise Prescription, and How They Influence Exercise-Induced Changes of Transcription Factors and Other Regulators of Mitochondrial Biogenesis

2018

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Physical inactivity represents the fourth leading risk factor for mortality, and it has been linked with a series of chronic disorders, the treatment of which absorbs ~ 85% of healthcare costs in developed countries. Conversely, physical activity promotes many health benefits; endurance exercise in particular represents a powerful stimulus to induce mitochondrial biogenesis, and it is routinely used to prevent and treat chronic metabolic disorders linked with sub-optimal mitochondrial characteristics. Given the importance of maintaining a healthy mitochondrial pool, it is vital to better characterize how manipulating the endurance exercise dose affects cellular mechanisms of exercise-induced mitochondrial biogenesis. Herein, we propose a definition of mitochondrial biogenesis and the techniques available to assess it, and we emphasize the importance of standardizing biopsy timing and the determination of relative exercise intensity when comparing different studies. We report an intensity-dependent regulation of exercise-induced increases in nuclear peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) protein content, nuclear phosphorylation of p53 (serine 15), and PGC-1α messenger RNA (mRNA), as well as training-induced increases in PGC-1α and p53 protein content. Despite evidence that PGC-1α protein content plateaus within a few exercise sessions, we demonstrate that greater training volumes induce further increases in PGC-1α (and p53) protein content, and that short-term reductions in training volume decrease the content of both proteins, suggesting training volume is still a factor affecting training-induced mitochondrial biogenesis. Finally, training-induced changes in mitochondrial transcription factor A (TFAM) protein content are regulated in a training volume-dependent manner and have been linked with training-induced changes in mitochondrial content.

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Section: Exercise-induced Changes In Nuclear Pgc-1α Protein Contentsupporting

confidence: 57%

Section: Exercise-induced Changes In Nuclear Pgc-1α Protein Contentmentioning

confidence: 99%

Principles of Exercise Prescription, and How They Influence Exercise-Induced Changes of Transcription Factors and Other Regulators of Mitochondrial Biogenesis

2018

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“…We observed a significant exercise-induced increase in PGC-1α protein content in both the nuclear and cytosolic fractions Pre-HVT, consistent with most previous research (24, 33, 43, 44). However, for the first time we report that these exercise-induced increases were absent post training in both subcellular fractions.…”

Section: Discussionsupporting

confidence: 92%

“…Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) is a key regulator of exercise-induced mitochondrial biogenesis (74) (for an in-depth analysis of the effects of exercise on mitochondrial biogenesis mediated by PGC-1α [and p53] the reader is referred to some excellent reviews; (17, 21, 35, 64)). In both rat (73) and human (24, 33, 43, 44) skeletal muscle, it has been observed that there is a post-exercise increase of PGC-1α protein content in the nucleus, where PGC-1α performs its transcriptional activity (62). Changes in PGC-1α protein content (30), as well as the content of other proteins (e.g., p53 (36)), contribute to the exercise-induced upregulation of PGC-1α mRNA (58).…”

Section: Introductionmentioning

confidence: 99%

Forty high-intensity interval training sessions blunt exercise-induced changes in the nuclear protein content of PGC-1α and p53 in human skeletal muscle

Granata

Oliveira

Little

et al. 2019

Preprint

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15Exercise-induced increases in peroxisome proliferator-activated receptor γ coactivator-1α (PGC-16 1α) and p53 protein content in the nucleus mediate the initial phase of exercise-induced 17 mitochondrial biogenesis. Here we investigated if exercise-induced increases in these and other 18 markers of mitochondrial biogenesis were altered after 40 sessions of twice-daily high-volume 19 high-intensity interval training (HVT) in human skeletal muscle. Vastus lateralis muscle biopsies 20 were collected from 10 healthy recreationally active participants before, immediately post, and 21 3h after a session of HIIE performed at the same absolute exercise intensity before and after 22HVT (Pre-HVT and Post-HVT, respectively). The protein content of common markers of 23 exercise-induced mitochondrial biogenesis were assessed in nuclear-and cytosolic-enriched 24 fractions by immunoblotting; mRNA contents of key transcription factors and mitochondrial 25 genes were assessed by qPCR. Despite exercise-induced increases in PGC-1α, p53, and plant 26 homeodomain finger-containing protein 20 (PHF20) protein content, the phosphorylation of p53 27 and acetyl-CoA carboxylase (p-p53 Ser15 and p-ACC Ser79 , respectively), and PGC-1α mRNA Pre-28 HVT, no significant changes were observed Post-HVT. Forty sessions of twice-daily high-29 intensity interval training blunted all of the measured exercise-induced molecular events 30 associated with mitochondrial biogenesis that were observed Pre-HVT. Future studies should 31 determine if this loss relates to the decrease in relative exercise intensity, habituation to the same 32 exercise stimulus, or a combination of both. 33 Keywords: endurance exercise, HIIT, mitochondrial adaptations, p53, PGC-1α 34 process that contributes to the initial phase of exercise-induced mitochondrial biogenesis (73), it 58 is important to better understand how the response of this transcriptional cofactor changes with 59 training. 60 p53 is another important regulator of exercise-induced mitochondrial biogenesis in human 61 skeletal muscle (64). Nuclear accumulation of p53 protein has been reported immediately (24), 62 or 3 hours (70), after a single session of exercise. While the mechanisms underlying the nuclear 63 accumulation of p53 are complex (47, 53), they have partly been attributed to phosphorylation of 64 p53 at serine 15 (p-p53 Ser15 ) (53) -a posttranslational modification that enhances p53 protein 65 stability (68) and prevents its nuclear export and cytosolic degradation (32, 53). However, once 66 again, these molecular events have only been investigated following a single exercise session, 67 and it is not known if they are altered by training. Given that the majority of the p53 activity 68 takes place in the nucleus (53), it is important to determine if the early events of the p53-69 mediated exercise-induced mitochondrial biogenesis are differentially regulated in this 70 subcellular compartment as the training intervention progresses. 71Therefore, the aim of our study was to investigate if a sessi...

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“…Trials consisted of 3 h of sitting in an environmentally controlled chamber (Darwin Chambers Company, St. Louis, MO) at three different temperatures (33 °C, 7 °C, and 20 °C) each at 60% relative humidity. The temperatures were determined in order to make a direct comparison to a previous study including the exercise stimulus (Heesch et al 2016). Each trial was separated by approximately one week.…”

Section: Methodsmentioning

confidence: 99%

Impact of hot and cold exposure on human skeletal muscle gene expression

Zak

Shute

Heesch

et al. 2017

Appl. Physiol. Nutr. Metab.

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Many human diseases lead to a loss of skeletal muscle metabolic function and mass. Local and environmental temperature can modulate the exercise-stimulated response of several genes involved in mitochondrial biogenesis and skeletal muscle function in a human model. However, the impact of environmental temperature, independent of exercise, has not been addressed in a human model. Thus, the purpose of this study was to compare the effects of exposure to hot, cold, and room temperature conditions on skeletal muscle gene expression related to mitochondrial biogenesis and muscle mass. METHODS Recreationally trained male subjects (n=12) had muscle biopsies taken from the vastus lateralis before and after 3 h exposure to hot (33 °C), cold (7 °C), or room temperature (20 °C) conditions. RESULTS Temperature had no effect on most of the genes related to mitochondrial biogenesis, myogenesis, or proteolysis (p > 0.05). Core temperature was significantly higher in hot and cold environments compared to room temperature (37.2 ± 0.1 °C, p = 0.001; 37.1 ± 0.1 °C, p = 0.013; 36.9 ± 0.1 °C, respectively). Whole body oxygen consumption was also significantly higher in hot and cold compared to room temperature (0.38 ± 0.01 L·min−1, p < 0.001; 0.52 ± 0.03 L·min−1, p < 0.001; 0.35 ± 0.01 L·min−1, respectively). CONCLUSIONS These data show that acute temperature exposure alone does not elicit significant changes in skeletal muscle gene expression. When considered in conjunction with previous research, exercise appears to be a necessary component to observe gene expression alterations between different environmental temperatures in humans.

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Transcriptional control, but not subcellular location, of PGC-1α is altered following exercise in a hot environment

Cited by 24 publications

References 49 publications

Principles of Exercise Prescription, and How They Influence Exercise-Induced Changes of Transcription Factors and Other Regulators of Mitochondrial Biogenesis

Principles of Exercise Prescription, and How They Influence Exercise-Induced Changes of Transcription Factors and Other Regulators of Mitochondrial Biogenesis

Forty high-intensity interval training sessions blunt exercise-induced changes in the nuclear protein content of PGC-1α and p53 in human skeletal muscle

Impact of hot and cold exposure on human skeletal muscle gene expression

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