Superior mitochondrial adaptations in human skeletal muscle after interval compared to continuous single-leg cycling matched for total work

MacInnis, Martin J.; Zacharewicz, Evelyn; Martin, Brian J.; Haikalis, Maria E.; Skelly, Lauren E.; Tarnopolsky, Mark A.; Murphy, Robyn M.; Gibala, Martin J.

doi:10.1113/jp272570

Cited by 224Cardiovascular and exercise physiologySports Performance and TrainingMuscle metabolism and nutrition

Superior mitochondrial adaptations in human skeletal muscle after interval compared to continuous single-leg cycling matched for total work

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MacInnis, Martin J., Zacharewicz, Evelyn, Martin, Brian J., Haikalis, Maria E., Skelly, Lauren E., Tarnopolsky, Mark A., Murphy, Robyn M., Gibala, Martin J.·2017·The Journal of Physiology

DOI 10.1113/jp272570PMC PMC5407978

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Abstract

Key points A classic unresolved issue in human integrative physiology involves the role of exercise intensity, duration and volume in regulating skeletal muscle adaptations to training. We employed counterweighted single‐leg cycling as a unique within‐subject model to investigate the role of exercise intensity in promoting training‐induced increases in skeletal muscle mitochondrial content. Six sessions of high‐intensity interval training performed over 2 weeks elicited greater increases in citrate synthase maximal activity and mitochondrial respiration compared to moderate‐intensity continuous training matched for total work and session duration. These data suggest that exercise intensity, and/or the pattern of contraction, is an important determinant of exercise‐induced skeletal muscle remodelling in humans. Abstract We employed counterweighted single‐leg cycling as a unique model to investigate the role of exercise intensity in human skeletal muscle remodelling. Ten young active men performed unilateral graded‐exercise tests to measure single‐leg and peak power ( W peak ). Each leg was randomly assigned to complete six sessions of high‐intensity interval training (HIIT) [4 × (5 min at 65% W peak and 2.5 min at 20% W peak )] or moderate‐intensity continuous training (MICT) (30 min at 50% W peak ), which were performed 10 min apart on each day, in an alternating order. The work performed per session was matched for MICT (143 ± 8.4 kJ) and HIIT (144 ± 8.5 kJ, P > 0.05). Post‐training, citrate synthase (CS) maximal activity (10.2 ± 0.8 vs . 8.4 ± 0.9 mmol kg protein −1 min −1 ) and mass‐specific [pmol O 2 •(s•mg wet weight) −1 ] oxidative phosphorylation capacities (complex I: 23.4 ± 3.2 vs . 17.1 ± 2.8; complexes I and II: 58.2 ± 7.5 vs . 42.2 ± 5.3) were greater in HIIT relative to MICT (interaction effects, P < 0.05); however, mitochondrial function [i.e. pmol O 2 •(s•CS maximal activity) −1 ] measured under various conditions was unaffected by training ( P > 0.05). In whole muscle, the protein content of COXIV (24%), NDUFA9 (11%) and mitofusin 2 (MFN2) (16%) increased similarly across groups (training effects, P < 0.05). Cytochrome c oxidase subunit IV (COXIV) and NADH:ubiquinone oxidoreductase subunit A9 (NDUFA9) were more abundant in type I than type II fibres ( P < 0.05) but training did not increase the content of COXIV, NDUFA9 or MFN2 in either fibre type ( P > 0.05). Single‐leg was also unaffected by training ( P > 0.05). In summary, single‐leg cycling performed in an interval compared to a continuous manner elicited superior mitochondrial adaptations in human skeletal muscle despite equal total work.

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The maintenance of mitochondrial respiratory function in the SR+EX group is consistent with previous reports of the potency of HIIE for improving mitochondrial respiratory function.
“The maintenance of mitochondrial respiratory function in the SR+EX group is consistent with previous reports of the potency of HIIE for improving mitochondrial respiratory function [26,55]”
From Exercise mitigates sleep-loss-induced changes in glucose tolerance, mitochondrial function, sarcoplasmic protein synthesis, and diurnal rhythms (2021) · cites this paper as [55]

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Training-Induced Changes in Mitochondrial Content and Respiratory Function in Human Skeletal Muscle
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Contribution of oxygen extraction fraction to maximal oxygen uptake in healthy young men
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Mitochondrial adaptations to high intensity interval training in older females and males.
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Locomotor Muscles in COPD: The Rationale for Rehabilitative Exercise Training
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Mitochondria Homeostasis and Oxidant/Antioxidant Balance in Skeletal Muscle—Do Myokines Play a Role?
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High-intensity interval, but not endurance, training induces muscle fiber type-specific subsarcolemmal lipid droplet size reduction in type 2 diabetic patients
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Effect of Cycle-Based High-Intensity Interval Training and Moderate to Moderate-Intensity Continuous Training in Adolescent Soccer Players
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Repeatability of exercise‐induced changes in mRNA expression and technical considerations for qPCR analysis in human skeletal muscle
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High-Intensity Interval Training Improves Cardiac Function by miR-206 Dependent HSP60 Induction in Diabetic Rats
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A fast, reliable and sample-sparing method to identify fibre types of single muscle fibres
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Acute cardiopulmonary responses to strength training, high-intensity interval training and moderate-intensity continuous training
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Endurance and Sprint Training Improve Glycemia and V˙O2peak but only Frequent Endurance Benefits Blood Pressure and Lipidemia
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Physiological responses to incremental, interval, and continuous counterweighted single-leg and double-leg cycling at the same relative intensities
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Moderate intensity continuous versus high intensity interval training: Metabolic responses of slow and fast skeletal muscles in rat
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Adaptation of Skeletal Muscles to Contractile Activity of Varying Duration and Intensity: The Role of PGC-1α
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High intensity interval training is associated with greater impact on physical fitness, insulin sensitivity and muscle mitochondrial content in males with overweight/obesity, as opposed to continuous endurance training: a randomized controlled trial.
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Fibre-specific mitochondrial protein abundance is linked to resting and post-training mitochondrial content in the muscle of men
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Efficacy of 10‐20‐30 training versus moderate‐intensity continuous training on HbA1c, body composition and maximum oxygen uptake in male patients with type 2 diabetes: A randomized controlled trial
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The Therapeutic Role of Exercise and Probiotics in Stressful Brain Conditions
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High-Intensity Interval Training Is Equivalent to Moderate-Intensity Continuous Training for Short- and Medium-Term Outcomes of Glucose Control, Cardiometabolic Risk, and Microvascular Complication Markers in Men With Type 2 Diabetes
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Abundance of ClC-1 chloride channel in human skeletal muscle: fiber type specific differences and effect of training
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Intellectual disability, exercise and aging: the IDEA study: study protocol for a randomized controlled trial
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Six weeks of high intensity cycle training reduces H2O2 emission and increases antioxidant protein levels in obese adults with risk factors for type 2 diabetes
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How do exercise training variables stimulate processes related to mitochondrial biogenesis in slow and fast trout muscle fibres?
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Effects of high-intensity interval training and moderate-intensity continuous training on mitochondrial dynamics in human skeletal muscle
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School-Based High-Intensity Interval Training Programs for Promoting Physical Activity and Fitness in Adolescents: A Systematic Review
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The physiology of interval training: a new target to HIIT
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Affective and perceptual responses during reduced-exertion high-intensity interval training (REHIT)
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HUMAN SKELETAL MUSCLE MITOCHONDRIAL RESPONSE TO INTERVAL TRAINING: ROLE OF EXERCISE INTENSITY
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Physiological adaptations to interval training and the role of exercise intensity
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Authors: MacInnis, M. J., Zacharewicz, E., Martin, B. J., Haikalis, M. E., Skelly, L. E., Tarnopolsky, M. A., Murphy, R. M., & Gibala, M. J.
Affiliations: McMaster University (CA)
La Trobe University (AU)
Corresponding author: Gibala, Martin J.
ORCID: MacInnis, Martin J.
Zacharewicz, Evelyn
Martin, Brian J.
Skelly, Lauren E.
Tarnopolsky, Mark A.
Murphy, Robyn M.
Gibala, Martin J.
Venue: The Journal of Physiology
Publisher: Wiley
Published: 2016-08-03
Volume: 595
Issue: 9
Pages: 2955-2968
ISSN: 0022-3751 (ISSN-L)
1469-7793
DOI: 10.1113/jp272570
PMC: PMC5407978
OpenAlex: W2470470829
Cited by: 224
References: 69
Citations by year: 2026: 15 · 2025: 18 · 2024: 24 · 2023: 23 · 2022: 22 · 2021: 21 · 2020: 28 · 2019: 28 · 2018: 25 · 2017: 18 · 2016: 2
FWCI: 49.79
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: The Journal of Physiology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Natural Sciences and Engineering Research Council of Canada (RGPIN‐2015‐04632)
Topics: Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
Health Sciences › Medicine › Orthopedics and Sports Medicine › Sports Performance and Training
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
Keywords: high-intensity interval training, moderate-intensity continuous training, exercise intensity, citrate synthase, mitochondrial respiration, oxidative phosphorylation, mitochondrial biogenesis, single-leg cycling, muscle remodeling, exercise volume, oxidative stress, peak power
MeSH terms: High-Intensity Interval Training, Adaptation, Physiological, Electron Transport, Humans, Leg, Male, Mitochondria, Muscle, Oxidative Phosphorylation, Oxygen Consumption, Muscle, Skeletal, Young Adult

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Superior mitochondrial adaptations in human skeletal muscle after interval compared to continuous single-leg cycling matched for total work

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