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

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. 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 V̇O2, peak and peak power (Wpeak ). Each leg was randomly assigned to complete six sessions of high-intensity interval training (HIIT) [4 × (5 min at 65% Wpeak and 2.5 min at 20% Wpeak )] or moderate-intensity continuous training (MICT) (30 min at 50% Wpeak ), 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 O2 •(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 O2 •(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 V̇O2, peak 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.

MacInnis MJ ，Zacharewicz E ，Martin BJ ，Haikalis ME ，Skelly LE ，Tarnopolsky MA ，Murphy RM ，Gibala MJ ... -  《-》

Preservation of skeletal muscle mitochondrial content in older adults: relationship between mitochondria, fibre type and high-intensity exercise training.

Ageing is associated with an upregulation of mitochondrial dynamics proteins mitofusin 2 (Mfn2) and mitochondrial dynamics protein 49 (MiD49) in human skeletal muscle with the increased abundance of Mfn2 being exclusive to type II muscle fibres. These changes occur despite a similar content of mitochondria, as measured by COXIV, NDUFA9 and complexes in their native states (Blue Native PAGE). Following 12 weeks of high-intensity training (HIT), older adults exhibit a robust increase in mitochondria content, while there is a decline in Mfn2 in type II fibres. We propose that the upregulation of Mfn2 and MiD49 with age may be a protective mechanism to protect against mitochondrial dysfunction, in particularly in type II skeletal muscle fibres, and that exercise may have a unique protective effect negating the need for an increased turnover of mitochondria. Mitochondrial dynamics proteins are critical for mitochondrial turnover and maintenance of mitochondrial health. High-intensity interval training (HIT) is a potent training modality shown to upregulate mitochondrial content in young adults but little is known about the effects of HIT on mitochondrial dynamics proteins in older adults. This study investigated the abundance of protein markers for mitochondrial dynamics and mitochondrial content in older adults compared to young adults. It also investigated the adaptability of mitochondria to 12 weeks of HIT in older adults. Both older and younger adults showed a higher abundance of mitochondrial respiratory chain subunits COXIV and NDUFA9 in type I compared with type II fibres, with no difference between the older adults and young groups. In whole muscle homogenates, older adults had higher mitofusin-2 (Mfn2) and mitochondrial dynamics protein 49 (MiD49) contents compared to the young group. Also, older adults had higher levels of Mfn2 in type II fibres compared with young adults. Following HIT in older adults, MiD49 and Mfn2 levels were not different in whole muscle and Mfn2 content decreased in type II fibres. Increases in citrate synthase activity (55%) and mitochondrial respiratory chain subunits COXIV (37%) and NDUFA9 (48%) and mitochondrial respiratory chain complexes (∼70-100%) were observed in homogenates and/or single fibres. These findings reveal (i) a similar amount of mitochondria in muscle from young and healthy older adults and (ii) a robust increase of mitochondrial content following 12 weeks of HIT exercise in older adults.

Wyckelsma VL ，Levinger I ，McKenna MJ ，Formosa LE ，Ryan MT ，Petersen AC ，Anderson MJ ，Murphy RM ... -  《-》

Physiological adaptations to interval training and the role of exercise intensity.

Interval exercise typically involves repeated bouts of relatively intense exercise interspersed by short periods of recovery. A common classification scheme subdivides this method into high-intensity interval training (HIIT; 'near maximal' efforts) and sprint interval training (SIT; 'supramaximal' efforts). Both forms of interval training induce the classic physiological adaptations characteristic of moderate-intensity continuous training (MICT) such as increased aerobic capacity (V̇O2 max ) and mitochondrial content. This brief review considers the role of exercise intensity in mediating physiological adaptations to training, with a focus on the capacity for aerobic energy metabolism. With respect to skeletal muscle adaptations, cellular stress and the resultant metabolic signals for mitochondrial biogenesis depend largely on exercise intensity, with limited work suggesting that increases in mitochondrial content are superior after HIIT compared to MICT, at least when matched-work comparisons are made within the same individual. It is well established that SIT increases mitochondrial content to a similar extent to MICT despite a reduced exercise volume. At the whole-body level, V̇O2 max is generally increased more by HIIT than MICT for a given training volume, whereas SIT and MICT similarly improve V̇O2 max despite differences in training volume. There is less evidence available regarding the role of exercise intensity in mediating changes in skeletal muscle capillary density, maximum stroke volume and cardiac output, and blood volume. Furthermore, the interactions between intensity and duration and frequency have not been thoroughly explored. While interval training is clearly a potent stimulus for physiological remodelling in humans, the integrative response to this type of exercise warrants further attention, especially in comparison to traditional endurance training.

MacInnis MJ ，Gibala MJ 《-》

Intermittent and continuous high-intensity exercise training induce similar acute but different chronic muscle adaptations.

High-intensity interval training (HIIT) performed in an 'all-out' manner (e.g. repeated Wingate tests) is a time-efficient strategy to induce skeletal muscle remodelling towards a more oxidative phenotype. A fundamental question that remains unclear, however, is whether the intermittent or 'pulsed' nature of the stimulus is critical to the adaptive response. In study 1, we examined whether the activation of signalling cascades linked to mitochondrial biogenesis was dependent on the manner in which an acute high-intensity exercise stimulus was applied. Subjects performed either four 30 s Wingate tests interspersed with 4 min of rest (INT) or a bout of continuous exercise (CONT) that was matched for total work (67 ± 7 kJ) and which required ∼4 min to complete as fast as possible. Both protocols elicited similar increases in markers of adenosine monophosphate-activated protein kinase (AMPK) and p38 mitogen-activated protein kinase activation, as well as Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) mRNA expression (main effects for time, P ≤ 0.05). In study 2, we determined whether 6 weeks of the CONT protocol (3 days per week) would increase skeletal muscle mitochondrial content to a similar extent to what we have previously reported after 6 weeks of INT. Despite similar acute signalling responses to the CONT and INT protocols, training with CONT did not increase the maximal activity or protein content of a range of mitochondrial markers. However, peak oxygen uptake was higher after CONT training (from 45.7 ± 5.4 to 48.3 ± 6.5 ml kg(-1) min(-1); P < 0.05) and 250 kJ time trial performance was improved (from 26:32 ± 4:48 to 23:55 ± 4:16 min:s; P < 0.001) in our recreationally active participants. We conclude that the intermittent nature of the stimulus is important for maximizing skeletal muscle adaptations to low-volume, all-out HIIT. Despite the lack of skeletal muscle mitochondrial adaptations, our data show that a training programme based on a brief bout of high-intensity exercise, which lasted <10 min per session including warm-up, and performed three times per week for 6 weeks, improved peak oxygen uptake in young healthy subjects.

Cochran AJ ，Percival ME ，Tricarico S ，Little JP ，Cermak N ，Gillen JB ，Tarnopolsky MA ，Gibala MJ ... -  《-》

Human skeletal muscle mitochondrial responses to single-leg intermittent or continuous cycle exercise training matched for absolute intensity and total work.

There is renewed interest in the potential for interval (INT) training to increase skeletal muscle mitochondrial content including whether the response differs from continuous (CONT) training. Comparisons of INT and CONT exercise are impacted by the manner in which protocols are "matched", particularly with respect to exercise intensity, as well as inter-individual differences in training responses. We employed single-leg cycling to facilitate a within-participant design and test the hypothesis that short-term INT training would elicit a greater increase in mitochondrial content than work- and intensity-matched CONT training. Ten young healthy adults (five males and five females) completed 12 training sessions over 4 weeks with each leg. Legs were randomly assigned to complete either 30 min of CONT exercise at a challenging sustainable workload (~50% single-leg peak power output; Wpeak) or INT exercise that involved 10 × 3-min bouts at the same absolute workload. INT bouts were interspersed with 1 min of recovery at 10% Wpeak and each CONT session ended with 10 min at 10% Wpeak. Absolute and mean intensity, total training time, and volume were thus matched between legs but the pattern of exercise differed. Contrary to our hypothesis, biomarkers of mitochondrial content including citrate synthase maximal activity, mitochondrial protein content and subsarcolemmal mitochondrial volume increased after CONT (p < 0.05) but not INT training. Both training modes increased single-leg Wpeak (p < 0.01) and time to exhaustion at 70% of single-leg Wpeak (p < 0.01). In a work- and intensity-matched comparison, short-term CONT training increased skeletal muscle mitochondrial content whereas INT training did not.

Skelly LE ，MacInnis MJ ，Bostad W ，McCarthy DG ，Jenkins EM ，Archila LR ，Tarnopolsky MA ，Gibala MJ ... -  《-》