Quantitative immunofluorescence microscopy of subcellular GLUT4 distribution in human skeletal muscle: effects of endurance and sprint interval training

The effects of training on silent mating-type information regulator 2 homolog 1 (SIRT1) activity and protein in relationship to peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and mitochondrial content were determined in human skeletal muscle. Six weeks of high-intensity interval training (∼1 h of 10 × 4 min intervals at 90% peak oxygen consumption separated by 2 min rest, 3 days per week) increased maximal activities of mitochondrial enzymes in skeletal muscle by 28% to 36% (citrate synthase, β-hydroxyacyl-coenzyme A dehydrogenase, and cytochrome c oxidase subunit IV) and PGC-1α protein (16%) when measured 4 days after training. Interestingly, total muscle SIRT1 activity (31%) and activity per SIRT1 protein (58%) increased despite decreased SIRT1 protein (20%). The present data demonstrate that exercise-induced mitochondrial biogenesis is accompanied by elevated SIRT1 activity in human skeletal muscle.

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

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00538.2010 ◽

2011 ◽

Vol 300 (6) ◽

pp. R1303-R1310 ◽

Cited By ~ 173

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.

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Skeletal Muscle Metabolic and Performance Adaptations After Short Sprint Interval Training (SIT).

Medicine & Science in Sports & Exercise ◽

10.1249/00005768-200405001-00092 ◽

2004 ◽

Vol 36 (Supplement) ◽

pp. S20

Author(s):

Kirsten A. Burgomaster ◽

George J.F. Heigenhauser ◽

Martin J. Gibala

Keyword(s):

Skeletal Muscle ◽

Interval Training ◽

Sprint Interval Training ◽

And Performance

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Effect of short-term sprint interval training on human skeletal muscle carbohydrate metabolism during exercise and time-trial performance

Journal of Applied Physiology ◽

10.1152/japplphysiol.01220.2005 ◽

2006 ◽

Vol 100 (6) ◽

pp. 2041-2047 ◽

Cited By ~ 198

Author(s):

Kirsten A. Burgomaster ◽

George J. F. Heigenhauser ◽

Martin J. Gibala

Keyword(s):

Skeletal Muscle ◽

Time Trial ◽

Interval Training ◽

Maximal Activity ◽

Sprint Interval Training ◽

Short Term ◽

Lactate Accumulation ◽

Pyruvate Oxidation ◽

Main Effect ◽

Before And After

Our laboratory recently showed that six sessions of sprint interval training (SIT) over 2 wk increased muscle oxidative potential and cycle endurance capacity (Burgomaster KA, Hughes SC, Heigenhauser GJF, Bradwell SN, and Gibala MJ. J Appl Physiol 98: 1895–1900, 2005). The present study tested the hypothesis that short-term SIT would reduce skeletal muscle glycogenolysis and lactate accumulation during exercise and increase the capacity for pyruvate oxidation via pyruvate dehydrogenase (PDH). Eight men [peak oxygen uptake (V̇o2 peak) = 3.8 ± 0.2 l/min] performed six sessions of SIT (4–7 × 30-s “all-out” cycling with 4 min of recovery) over 2 wk. Before and after SIT, biopsies (vastus lateralis) were obtained at rest and after each stage of a two-stage cycling test that consisted of 10 min at ∼60% followed by 10 min at ∼90% of V̇o2 peak. Subjects also performed a 250-kJ time trial (TT) before and after SIT to assess changes in cycling performance. SIT increased muscle glycogen content by ∼50% (main effect, P = 0.04) and the maximal activity of citrate synthase (posttraining: 7.8 ± 0.4 vs. pretraining: 7.0 ± 0.4 mol·kg protein −1·h−1; P = 0.04), but the maximal activity of 3-hydroxyacyl-CoA dehydrogenase was unchanged (posttraining: 5.1 ± 0.7 vs. pretraining: 4.9 ± 0.6 mol·kg protein −1·h−1; P = 0.76). The active form of PDH was higher after training (main effect, P = 0.04), and net muscle glycogenolysis (posttraining: 100 ± 16 vs. pretraining: 139 ± 11 mmol/kg dry wt; P = 0.03) and lactate accumulation (posttraining: 55 ± 2 vs. pretraining: 63 ± 1 mmol/kg dry wt; P = 0.03) during exercise were reduced. TT performance improved by 9.6% after training (posttraining: 15.5 ± 0.5 vs. pretraining: 17.2 ± 1.0 min; P = 0.006), and a control group ( n = 8, V̇o2 peak = 3.9 ± 0.2 l/min) showed no change in performance when tested 2 wk apart without SIT (posttraining: 18.8 ± 1.2 vs. pretraining: 18.9 ± 1.2 min; P = 0.74). We conclude that short-term SIT improved cycling TT performance and resulted in a closer matching of glycogenolytic flux and pyruvate oxidation during submaximal exercise.

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

10.1101/580373 ◽

2019 ◽

Author(s):

Cesare Granata ◽

Rodrigo S.F. Oliveira ◽

Jonathan P. Little ◽

David J. Bishop

Keyword(s):

Skeletal Muscle ◽

Protein Content ◽

Mitochondrial Biogenesis ◽

Exercise Intensity ◽

High Intensity ◽

Human Skeletal Muscle ◽

Interval Training ◽

High Intensity Interval Training ◽

High Intensity Interval ◽

Exercise Induced

ABSTRACTExercise-induced increases in peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and p53 protein content in the nucleus mediate the initial phase of exercise-induced mitochondrial biogenesis. Here we investigated if exercise-induced increases in these and other markers of mitochondrial biogenesis were altered after 40 sessions of twice-daily high-volume high-intensity interval training (HVT) in human skeletal muscle. Vastus lateralis muscle biopsies were collected from 10 healthy recreationally active participants before, immediately post, and 3h after a session of HIIE performed at the same absolute exercise intensity before and after HVT (Pre-HVT and Post-HVT, respectively). The protein content of common markers of exercise-induced mitochondrial biogenesis were assessed in nuclear- and cytosolic-enriched fractions by immunoblotting; mRNA contents of key transcription factors and mitochondrial genes were assessed by qPCR. Despite exercise-induced increases in PGC-1α, p53, and plant homeodomain finger-containing protein 20 (PHF20) protein content, the phosphorylation of p53 and acetyl-CoA carboxylase (p-p53Ser15 and p-ACCSer79, respectively), and PGC-1α mRNA Pre-HVT, no significant changes were observed Post-HVT. Forty sessions of twice-daily high-intensity interval training blunted all of the measured exercise-induced molecular events associated with mitochondrial biogenesis that were observed Pre-HVT. Future studies should determine if this loss relates to the decrease in relative exercise intensity, habituation to the same exercise stimulus, or a combination of both.

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Skeletal Muscle Metabolic and Performance Adaptations After Short Sprint Interval Training (SIT).

Medicine & Science in Sports & Exercise ◽

10.1097/00005768-200405001-00092 ◽

2004 ◽

Vol 36 (Supplement) ◽

pp. S20 ◽

Cited By ~ 1

Author(s):

Kirsten A. Burgomaster ◽

George J.F. Heigenhauser ◽

Martin J. Gibala

Keyword(s):

Skeletal Muscle ◽

Interval Training ◽

Sprint Interval Training ◽

And Performance

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Acute upregulation of PGC-1α mRNA correlates with training-induced increases in SDH activity in human skeletal muscle

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2016-0463 ◽

2017 ◽

Vol 42 (6) ◽

pp. 656-666 ◽

Cited By ~ 6

Author(s):

Jacob T. Bonafiglia ◽

Brittany A. Edgett ◽

Brittany L. Baechler ◽

Matthew W. Nelms ◽

Craig A. Simpson ◽

...

Keyword(s):

Skeletal Muscle ◽

Mrna Expression ◽

Human Skeletal Muscle ◽

Interval Training ◽

Capillary Density ◽

Oxidative Capacity ◽

Peak Oxygen Uptake ◽

Fibre Type Composition ◽

Type Composition ◽

Acute Responses

The purpose of the present study was to determine if acute responses in PGC-1α, VEGFA, SDHA, and GPD1–2 mRNA expression predict their associated chronic skeletal muscle molecular (SDH–GPD activity and substrate storage) and morphological (fibre-type composition and capillary density) adaptations following training. Skeletal muscle biopsies were collected from 14 recreationally active men (age: 22.0 ± 2.4 years) before (PRE) and 3 h after (3HR) the completion of an acute bout of sprint interval training (SIT) (eight 20-s intervals at ∼170% peak oxygen uptake work rate separated by 10 s of recovery). Participants then completed 6 weeks of SIT 4 times per week with additional biopsies after 2 (MID) and 6 (POST) weeks of training. Acute increases in PGC-1α mRNA strongly predicted increases in SDH activity (a marker of oxidative capacity) from PRE and MID to POST (PRE–POST: r = 0.81, r2 = 0.65, p < 0.01; MID–POST: r = 0.79, r2 = 0.62, p < 0.01) and glycogen content from MID to POST (r = 0.60, r2 = 0.36, p < 0.05). No other significant relationships were found between acute responses in PGC-1α, VEGFA, SDHA, and GPD1–2 mRNA expression and chronic adaptations to training. These results suggest that acute upregulation of PGC-1α mRNA relates to the magnitude of subsequent training-induced increases in oxidative capacity, but not other molecular and morphological chronic skeletal muscle adaptations. Additionally, acute mRNA responses in PGC-1α correlated with VEGFA, but not SDHA, suggesting a coordinated upregulation between PGC-1α and only some of its proposed targets in human skeletal muscle.

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