A key regulator of oxidative enzyme expression in a number of cell types, including skeletal muscle, is the peroxisome proliferator-activated receptor-γ coactivator 1 alpha (PGC-1α). PGC-1 is a transcriptional coactivator that recruits histone acetyltransferase (HAT) enzymes to a number of specific DNA-bound transcription factors within gene regulatory promoter regions (15). Recruitment of HATs to these regions alters the local chromosome structure to one that favors transcription. The effect of PGC-1α on skeletal muscle phenotype can be dramatic, with genetic overexpression of PGC-1α inducing a fast to slow fiber-type conversion (17). This change in phenotype is accompanied by enhanced mitochondrial enzyme expression and an increase in time to fatigue when electrically stimulated (17). Endurance exercise increases PGC-1α activity (18) and expression (26), suggesting that PGC-1α could be a critical component of the adaptive response to this form of training. Recently, we (7) found that 6 wk of low-volume HIT increased PGC-1α protein content in human skeletal muscle similar to high-volume endurance training (Fig. 5). The potency of interval-based training in this regard is supported by the work of Terada et al. (23), who showed increased skeletal muscle PGC-1α protein content after a single bout of high-intensity intermittent swim exercise in rats.
PGC-1α activity is acutely regulated by p160myb, a powerful repressor of PGC-1α function (10). Phosphorylation of PGC-1α disrupts the interaction with p160myb, allowing PGC-1 to associate with transcriptional regulators, which augments PGC-1α activity. The p38 mitogen-activated protein kinase (MAPK) is one kinase that can phosphorylate PGC-1α and thereby regulate PGC-1α activity (10). This pathway is a member of the larger MAPK family and is activated by cellular stresses including aerobic-type exercise (25). Although the exact mechanism by which exercise activates p38 MAPK is unknown, it likely involves phosphorylation by an upstream kinase cascade. Indices of PGC-1α activation during exercise are associated with increases in p38 phosphorylation in the nucleus (18). Furthermore, constitutive activation of p38 MAPK in fast muscle fibers results in enhanced mitochondrial enzyme expression (1), suggesting that p38 MAPK is an important mediator of the adaptive response to exercise.
Although there is consensus regarding the importance of physical activity, the minimum dose necessary to improve health status is unclear (4). Public health guidelines generally recommend 30-60 min of moderate-intensity exercise on most days of the week. However, despite overwhelming scientific evidence that regular physical activity is effective in the prevention of chronic diseases and premature death, most adults fail to meet even the minimum physical activity guidelines. Countless studies have shown that the most commonly cited reason for not exercising is a "lack of time" (12). This finding is ubiquitous; regardless of age, ethnicity, sex, or health status, people report that a lack of time is the primary reason for their failure to exercise on a regular basis. Given that lack of time is such a common barrier to exercise participation, exercise prescription innovations that yield benefits with minimal time commitments represent a potentially valuable approach to increasing population activity levels and population health. HIT is often dismissed outright as unsafe, unpractical, or intolerable for many individuals. However, there is growing appreciation of the potential for intense interval-based training to stimulate improvements in health and fitness in a range of populations, including persons with various disease conditions (20,24). In addition, some data suggest that a low-frequency high-intensity approach to training is associated with greater long-term adherence as compared with a high-frequency low-intensity program (14).
Our recent studies should not be interpreted to suggest that low-volume interval training provides all of the benefits normally associated with traditional endurance training. The duration of the training programs in most of our published work to date was relatively short (up to 6 wk), and it remains to be determined whether similar adaptations are manifest after many months of low-volume interval and high-volume continuous training. It is possible that the time course for physiological adjustments differs between training protocols; the very intense nature of interval training may stimulate relatively rapid changes, whereas the adaptations induced by traditional endurance training may occur more slowly. Second, the Wingate-based training model that we have used requires a specialized ergometer and an extremely high level of subject motivation. Given the extreme nature of the exercise, it is doubtful that the general population could safely or practically adopt the model. Like the recent work by Talanian et al. (22), future studies should examine modified interval-based approaches to identify the optimal combination of training intensity and volume necessary to induce adaptations in a practical time-efficient manner. Finally, to date, we have only examined selected variables in skeletal muscle, and future studies should examine whether low-volume interval training induces other physiological adaptations normally associated with prolonged periods of moderate-intensity training. HIT may differ from traditional endurance training with respect to changes induced in the cardiovascular and respiratory systems, metabolic control in other organs (e.g., liver, adipose tissue), and protection from disorders associated with chronic inactivity (e.g., insulin resistance, lipid dysregulation).
Elite endurance athletes have long appreciated the role of high-intensity interval exercise as part of a comprehensive training program. Recent evidence suggests that - in young healthy persons of average fitness - intense interval exercise is a time-efficient strategy to stimulate a number of skeletal muscle adaptations that are comparable to traditional endurance training. However, fundamental questions remain regarding the minimum volume of exercise necessary to improve physiological well-being in various populations, the effectiveness of alternative (less extreme) interval-training strategies, and the precise nature and magnitude of adaptations that can be elicited and maintained over the long-term. A comprehensive evaluation of the physiological adaptations induced by different interval-training strategies in a wide range of populations will permit evidence-based recommendations that may provide an alternative to current exercise prescriptions for time-pressed individuals.
Work cited from the corresponding author's laboratory was supported by the Natural Sciences and Engineering Research Council of Canada and by an American College of Sports Medicine Foundation Research Endowment Grant. Sean L. McGee is a National Health and Medical Research Council Peter Doherty Fellow (400446).
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