Introduction: High-intensity interval training (HIT) increases skeletal muscle oxidative capacity similar to traditional endurance training, despite a low total exercise volume. Much of this work has focused on young active individuals, and it is unclear whether the results are applicable to older less active populations. In addition, many studies have used "all-out" variable-load exercise interventions (e.g., repeated Wingate tests) that may not be practical for all individuals. We therefore examined the effect of a more practical low-volume submaximal constant-load HIT protocol on skeletal muscle oxidative capacity and insulin sensitivity in middle-aged adults, who may be at a higher risk for inactivity-related disorders.
Methods: Seven sedentary but otherwise healthy individuals (three women) with a mean ± SD age, body mass index, and peak oxygen uptake (V˙O2peak) of 45 ± 5 yr, 27 ± 5 kg·m−2, and 30 ± 3 mL·kg−1·min-1 performed six training sessions during 2 wk. Each session involved 10 × 1-min cycling at ∼60% of peak power achieved during a ramp V˙O2peak test (eliciting ∼80%-95% of HR reserve) with 1 min of recovery between intervals. Needle biopsy samples (vastus lateralis) were obtained before training and ∼72 h after the final training session.
Results: Muscle oxidative capacity, as reflected by the protein content of citrate synthase and cytochrome c oxidase subunit IV, increased by ∼35% after training. The transcriptional coactivator peroxisome proliferator-activated receptor γ coactivator 1α was increased by ∼56% after training, but the transcriptional corepressor receptor-interacting protein 140 remained unchanged. Glucose transporter protein content increased ∼260%, and insulin sensitivity, on the basis of the insulin sensitivity index homeostasis model assessment, improved by ∼35% after training.
Conclusions: Constant-load low-volume HIT may be a practical time-efficient strategy to induce metabolic adaptations that reduce the risk for inactivity-related disorders in previously sedentary middle-aged adults.
1Exercise Metabolism Research Group, Department of Kinesiology, McMaster University, Hamilton, Ontario, CANADA; and 2Department of Pediatrics and Medicine, McMaster University, Hamilton, Ontario, CANADA
Address for correspondence: Martin Joseph Gibala, Ph.D., Department of Kinesiology, McMaster University, Ivor Wynne Centre, Room 219, 1280 Main St., Hamilton, Ontario, Canada L8S 4K1; E-mail: email@example.com.
Submitted for publication September 2010.
Accepted for publication March 2011.
Regular endurance exercise training is an effective strategy to improve insulin sensitivity (6,18) and reduce the risk of developing metabolic disorders such as type 2 diabetes (T2D) (38). Although the pathophysiology of insulin resistance is not fully understood, increased skeletal muscle oxidative and glucose transport capacities resulting from exercise training have been linked to improved insulin sensitivity (6,13,15,17). These and other adaptations may ameliorate the effects of sedentary living on skeletal muscle energy metabolism (12) and thereby reduce the risk of chronic disease and premature death (3,38).
Despite the beneficial effect of endurance exercise training on cardiorespiratory and metabolic health (13,16), many individuals consider its lengthy time requirement a barrier to performing regular exercise (4,42). Therefore, less time-consuming interventions may be more attractive. We (7-9,11) and others (1,36) have demonstrated that high-intensity interval training (HIT) is a potent stimulus to elicit adaptations that resemble those of traditional endurance training despite a substantial reduction in the total time commitment and exercise volume. Direct comparisons of low-volume HIT and traditional high-volume endurance training suggest that both protocols lead to similar increases in muscle mitochondrial content and endurance exercise performance (8,11). Low-volume HIT also rapidly increases skeletal muscle glucose transporter (GLUT4) protein content (7,24). Two recent studies (1,36) also reported a significant improvement in insulin sensitivity after 2 wk of HIT. Our previous research (e.g., Burgomaster et al. (7-9) and Gibala et al. ) and works from other groups (1,36) have used an HIT model that involves repeated "all-out" maximal-intensity cycling efforts on a specialized ergometer (i.e., repeated Wingate tests). This type of training requires a specialized ergometer and a high level of motivation, and the extremely demanding nature of the exercise can induce feelings of severe fatigue. All-out interval training may therefore be impractical or unsuitable for some individuals, and others have called for the development of alternative HIT strategies that might be more suitable for specific populations, depending on age, health status, and psychology (10). Furthermore, the majority of research investigating the metabolic effects of HIT (e.g., Babraj et al. (1), Burgomaster et al. (7-9), Gibala et al. (11), and Little et al. (24)) has been conducted in young active individuals (≤30 yr), and it is unclear whether the findings can be applied to sedentary middle-aged individuals, a population more at risk of developing chronic disease (42).
The primary purpose of this study was to examine skeletal muscle remodeling in response to short-term low-volume HIT in previously sedentary middle-aged adults. The training protocol was based on our recent work in young healthy individuals (24) and was designed to be more practical as compared with Wingate-based training, which requires a specialized ergometer and an all-out effort. We hypothesized that HIT would stimulate mitochondrial biogenesis, as evidenced by changes in the protein content of the common marker enzymes citrate synthase (CS) and cytochrome c oxidase (COX), and alter the expression of proteins linked to this adaptive response including peroxisome proliferator-activated receptor γ coactivator (PGC) 1α and receptor-interacting protein (RIP) 140 (2,23,31). A secondary purpose was to explore the potential clinical significance of low-volume HIT by determining the insulin sensitivity index (ISI) using the homeostasis model assessment (HOMA) method (26) before and after training. We hypothesized that ISI (HOMA) would improve after the 2-wk HIT protocol and that this would be accompanied by an increased total GLUT4 content in skeletal muscle.
Seven sedentary but otherwise healthy men (n = 4) and women volunteered to participate in the study (age = 45 ± 5 yr, body mass index = 27 ± 5 kg·m−2, peak oxygen uptake (V˙O2peak) = 30 ± 3 mL·kg−1·min−1). Eligibility for the study was confirmed by medical screening including the completion of a general health questionnaire and the following measurements: height, weight, resting HR, blood pressure, fasting plasma glucose, and an ECG. Preliminary screening determined that participants were (a) sedentary, defined as not having participated in a regular exercise program (i.e., two or fewer sessions per week and ≤30 min per session) for at least 1 yr before the study, and (b) did not present any contraindications to beginning an exercise program. The participants did not partake in any form of regular physical activity and did not meet the minimum level of physical activity recommended by leading public health agencies including Health Canada and the American College of Sports Medicine. The procedures for each visit were explained to participants on arrival at the laboratory. Participants were informed of the purpose and potential risks associated with the study before providing written informed consent. The experiment was approved by the Hamilton Health Sciences/Faculty of Health Sciences Research Ethics Board.
Waist circumference was measured using a nonelastic tape at the midpoint between the iliac crest and the bottom of the rib cage while participants stood in a relaxed position with arms at their side. A stadiometer and physician's scale were used to measure height and weight, and body mass index was calculated (kg·m−2). Resting HR and blood pressure were measured by an automatic inflation monitor (Spot Vital Signs®; Welch Allyn, Mississauga, Canada). Finally, resting and postexercise 12-lead ECG were conducted on the same day as the V˙O2peak test using an ECG apparatus (MAC; Marquette Electronics, Inc., Milwaukee, WI).
Participants performed an incremental exercise test to exhaustion on an electronically braked cycle ergometer (Lode Excalibur Sport V2.0; Groningen, The Netherlands) to determine V˙O2peak and peak power output (Wmax). After a 3-min cycling warm-up at 50 W, the workload was increased by 1 W every 2 s until participants reached volitional exhaustion or the pedal cadence decreased to <40 revolutions per minute because power output is not valid below this cadence according to the manufacturer's specifications. A metabolic cart with an online gas collection system (MOXUS Modular V˙O2 System; AEI Technologies, Pittsburgh, PA) was used to acquire data to quantify oxygen consumption, carbon dioxide production, and substrate oxidation via RER. The coefficient of variation (CV) for V˙O2peak measurements using the MOXUS System in our laboratory is ≤4% (9). V˙O2peak and Wmax corresponded to the highest oxygen consumption and peak power output values achieved during a 15-s period, respectively. The gas analyzers and turbine volume were calibrated before each test using standard reference gases (VitalAire, Mississauga, Canada) and a 3-L syringe obtained from the metabolic cart manufacturer (AEI Technologies), respectively. HR was monitored continuously throughout the test by telemetry with a Polar A3 monitor (Polar, Lake Success, NY). After completion of the incremental exercise test, participants returned to the laboratory on two occasions to verify the workload eliciting 60% Wmax and become familiarized with the training protocol.
Fasting blood and resting muscle biopsy sampling.
Although sedentary to begin with, participants were instructed to avoid any physical activity aside from activities for at least 24 h before the blood and muscle sampling procedures. For blood sampling, subjects reported to the laboratory in the morning (∼8:00 a.m.) after an overnight (≥10 h) fast. A resting blood sample was obtained by venipuncture from an antecubital vein and treated according to manufacturer's instructions (Vacutainer®; BD, Mississauga, Canada). The lateral portion of one thigh was prepared for the extraction of muscle biopsy samples from the vastus lateralis (5). The procedure was initiated by injection of a local anesthetic (2% lidocaine) followed by a small incision in the skin and underlying tissues. The obtained biopsy samples were immediately frozen in liquid nitrogen and stored at −80°C until subsequent analysis. The final fasting blood and muscle samples were obtained ∼72 h after the last training bout using procedures identical in all respects to preexercise baseline trials.
The training protocol was initiated at least 3 d after the pretraining muscle biopsy procedure. Participants completed six sessions of high-intensity interval exercise on a cycle ergometer (Lode) during a 2-wk period, with each session interspersed by 1-2 d of recovery (i.e., training occurred on Monday, Wednesday, and Friday of each week). Each session consisted of a 3-min warm-up at 50 W, followed by a series of 10 × 60-s high-intensity cycling efforts interspersed with 60 s of recovery and terminated with a 5-min cool-down at 50 W. The workload during each interval was set at 60% of peak power achieved during the V˙O2peak test. Mean power output during training was ∼150 W, and this elicited ∼80% of HR reserve at the end of the first 60-s interval, climbing to ∼95% of the HR reserve after the last interval. During recovery between the high-intensity efforts, subjects cycled at a fixed resistance of 30 W. Training took place in a dedicated (research only) exercise testing and training laboratory located within the Department of Kinesiology at McMaster University, and sessions were directly supervised by a certified kinesiologist. All subjects completed all prescribed exercise bouts.
Physical activity and nutritional controls.
Participants were instructed to continue their normal daily activity (i.e., remain sedentary) throughout the experimental period and to refrain from any structured physical activity except for the prescribed training program. Participants were also instructed to maintain their habitual diet during the 2-wk training period. To control for any diet-induced variability in fasting blood or resting biopsy measures, participants recorded their dietary intake for 24 h before pretraining sampling procedures and replicated the diet using the same types and quantities of food before the posttraining procedures. Subsequent dietary analyses (The Food Processor SQL 9.8; ESHA Research, Salem, OR) revealed no differences in the total energy or macronutrient content of diets before or after training (data not shown).
Muscle and blood analyses.
The total protein content of CS, cytochrome c oxidase (COX) subunits II and IV, GLUT4, PGC-1α, RIP140, phosphorylated Akt (p-Akt), and total Akt were quantified by standard Western blotting procedures as we have previously described (10,12,24). A rabbit polyclonal antibody for CS was a kind gift from Dr. Brian Robinson (Hospital for Sick Children, Toronto, Canada). COX antibodies were from MitoSciences (Eugene, OR). The GLUT4 antibody was from Chemicon/Millipore (Billerica, MA). The PGC-1α, p-Akt, and total Akt antibodies were purchased from Cell Signaling Technology (Beverly, MA), and the RIP140 antibody was from Sigma (St. Louis, MO). Muscle biopsy samples were homogenized in a radioimmunoprecipitation assay buffer supplemented with protease (Complete Mini®; Roche Applied Science, Laval, Canada) and phosphatase (PhosSTOP®; Roche Applied Science) inhibitors and protein concentration of homogenates determined using a commercial assay kit (Pierce BCA Protein Assay Kit; Rockford, IL). The CV for protein quantification for duplicate samples is <5.0% in our laboratory. Proteins were denatured by addition of 4× Laemmli buffer and heating to 95°C for 5 min. Equal amounts of protein (5-20 μg) were separated by electrophoresis on 7.5%-12.5% sodium dodecyl sulfate polyacrylamide gel electrophoresis gels for ∼2 h at 100 V. Proteins were electrotransferred to nitrocellulose membranes at 100 V for 1 h. Ponceau S staining was used to verify and control for equal transfer and loading. After blocking in 5% milk Tris-buffered saline-Tween 20 (TBS-T), membranes were incubated with primary antibodies for 2 h at room temperature (CS, COX II, COX IV) or overnight at 4°C (GLUT4, PGC-1α, RIP140, p-Akt, Akt) in 3% milk or bovine serum albumin. Membranes were then washed for 3 × 5 min in TBS-T and incubated inappropriate species-specific secondary antibodies at 1:10,000 dilution in 3% milk TBS-T for 1 h at room temperature. After 3 × 15-min washes, blots were developed using a chemiluminescent substrate (SuperSignal® West Dura; Pierce) and exposed to an x-ray film or visualized using a Fluorochem® SP Imaging system and software (Alpha Innotech Corporation, San Leandro, CA). After measurement of p-Akt, membranes were stripped by incubating in Restore Western Blot Stripping Buffer (Pierce) with vigorous shaking for 45 min, reblocked in 3% milk TBS-T, and probed for total Akt. Band intensities were quantified using the National Institutes of Health ImageJ analysis software.
Mixed venous blood samples were collected into tubes that contained sodium heparin or a clot activator (Vacutainer; BD). Collection tubes were immediately inverted eight or five times as per the manufacturer's directions and then placed on ice or left to clot at room temperature as instructed. Blood samples were then centrifuged for 10 min at 1750g. The resulting plasma was immediately analyzed for blood glucose (Ascensia Contour; Bayer, Tarrytown, NY). The serum was stored at −80°C for subsequent analysis of insulin using a commercially available assay kit (Insulin EIA; ALPCO Diagnostics, Salem, NH). All samples were run in triplicate, with the CV being <4.0% for glucose and <3.0% for insulin. Insulin sensitivity was estimated using the ISI (HOMA) method using the following equation previously described by Matsuda and DeFronzo (26): ISI (HOMA) = k/(fasting glucose × fasting insulin), where k = 22.5 × 18.
Differences between pre- and posttraining values for all variables were analyzed using paired-samples t-tests. All data are presented as mean ± SD. Significance was set at P < 0.05.
Skeletal muscle adaptations.
The protein content of CS and COX IV increased by 31% and 39%, respectively, after training (P < 0.05, Fig. 1). COX II content tended to increase (∼16%) after training, but this did not reach statistical significance (P = 0.10, data not shown). Total GLUT4 content increased by ∼260% after training (P < 0.001, Fig. 2). PGC-1α protein was increased by 56% after training (P = 0.01, Fig. 3A), but there were no effects of training on RIP140 protein content (P > 0.05, Fig. 3B). Basal Akt phosphorylation was reduced by ∼67% after training (P < 0.05, Fig. 4), whereas total Akt protein content was not significantly different (P = 0.80).
Fasting insulin, glucose, and ISI (HOMA).
Fasting insulin concentration decreased by 16% after training (after = 6.6 ± 2.9 vs before = 8.1 ± 3.5 μIU·mL−1, P < 0.01), whereas fasting glucose concentration was not significantly different despite a tendency to decline (after = 4.3 ± 0.5 vs before = 4.9 ± 0.3 mmol·L−1, P = 0.09). As a result, insulin sensitivity calculated by ISI (HOMA) improved after training by 35% (P < 0.05, Fig. 5).
The major novel finding from the present investigation was that six sessions of constant-load HIT performed during 2 wk improved insulin sensitivity and increased markers of skeletal muscle mitochondrial content and glucose transport capacity in previously sedentary middle-aged adults. These beneficial adaptations occurred despite a low total exercise volume and training time commitment. To further elucidate the potential mechanisms that promote the muscle adaptive response, we measured the protein levels of PGC-1α and RIP140, which are positive and negative regulators of mitochondrial and metabolic gene expression, respectively. PGC-1α protein increased after training, yet there were no changes in total RIP140 content. These data support the notion that low-volume constant-load HIT is a time-efficient strategy to promote mitochondrial biogenesis and induce metabolic adaptations that may reduce the risk for insulin resistance and T2D in previously sedentary middle-aged adults.
Low-volume HIT rapidly improves insulin sensitivity.
The importance of exercise intensity in preventing and treating T2D is well recognized (39). Fifteen weeks of high-intensity interval exercise was previously shown to reduce markers of insulin resistance in young women (41), and Babraj et al. (1) demonstrated that insulin sensitivity-measured indirectly using oral glucose tolerance tests-was improved after 2 wk of Wingate-based HIT in young recreationally active men. More recently, Richards et al. (36) reported improved insulin sensitivity, on the basis of hyperinsulinemic euglycemic clamp measurements, in previously sedentary or recreationally active young adults after an identical HIT protocol. To our knowledge, the present study is the first to report rapid improvements in an indirect measure of insulin sensitivity after low-volume HIT in previously sedentary middle-aged adults who may be at a higher risk for developing insulin resistance and T2D. Unlike Wingate-based training, the 2-wk HIT protocol in the present study used a lower-intensity constant-load protocol as opposed to all-out efforts. Our HIT program elicited changes in insulin sensitivity that are generally observed after high-volume endurance training (6,18,30). Although it has been suggested that duration is more important than intensity when prescribing exercise to improve insulin sensitivity (18), the present study and other works (1,41) suggest an important role for exercise intensity.
The mechanisms by which exercise training improves insulin sensitivity are not fully understood, but changes in muscle mitochondrial capacity may be one factor. People with insulin resistance and T2D have been shown to have reduced mitochondrial gene expression (27,32) and impaired mitochondrial capacity (33). The protein content of representative mitochondrial enzymes measured in resting muscle biopsies increased by approximately 35% after training, which is comparable to changes reported in young active individuals after several weeks of Wingate-based HIT (7) or traditional high-volume endurance exercise (e.g., Burgomaster et al. (8) and Pilegaard et al. ). Although previous research has supported a link between improvements in muscle oxidative capacity and insulin sensitivity (6,40), the hypothesis that reduced mitochondrial capacity plays a causative role in insulin resistance (28) has come under scrutiny lately (14). Even if reduced mitochondrial capacity is not causative, increased mitochondrial ATP production in response to exercise training is still linked with improvements in insulin sensitivity (19). Another possible mechanism that improves insulin sensitivity after exercise involves increased skeletal muscle glucose transport capacity (15,17,35). Whole muscle GLUT4 protein content increased by more than twofold after training in the present study, which is comparable to that observed after short-term high-volume endurance training (17). In rodents, the increase in total skeletal muscle GLUT4 content after training is proportional to glucose transport capacity in response to a given concentration of insulin (35).
Insight into potential regulators of the muscle adaptive response.
Several lines of evidence have suggested that reduced PGC-1α in skeletal muscle might be implicated in the pathogenesis of insulin resistance and T2D (25,27,32). PGC-1α coactivates several transcription factors to coordinately upregulate a program of mitochondrial and metabolic gene transcription in muscle (2,23). PGC-1α mRNA expression is robustly increased in the postexercise recovery period after endurance (34) and interval (12) exercise, and training has been shown to increase PGC-1α protein expression in some studies (8,29). For these reasons, PGC-1α is hypothesized to play a critical role in the muscle's adaptive response to exercise (43). Furthermore, modest overexpression of PGC-1α by electrotransfection of the PGC-1α gene into skeletal muscle of rats increases mitochondrial content, GLUT4 protein, and muscle insulin sensitivity (2), and induction of PGC-1α can rescue cultured muscle cells from lipotoxicity (20). Therefore, interventions that increase PGC-1α in skeletal muscle would seem to have beneficial effects on insulin sensitivity and metabolic health. The increase in skeletal muscle PGC-1α protein content seen in the present study suggests that low-volume HIT is a potent strategy. However, it is currently unclear whether the increase in PGC-1α is required to direct an increase in mitochondrial biogenesis and GLUT4 expression or whether this response might play a supportive role in maintaining such increases. Wright et al. (43) demonstrated that activation of existing PGC-1α protein that caused an increase in nuclear abundance enabled PGC-1α to coactivate various transcription factors and mediate the initial stages of the adaptive response. Furthermore, despite a lower basal level of mitochondrial content, it seems as though a strain of PGC-1α-null mice respond in a similar manner as wild-type animals by increasing mitochondrial biogenesis after endurance exercise training (21). Therefore, it is likely that PGC-1α is one of several transcriptional regulators that help control the adaptive response to exercise in skeletal muscle. For this reason, we also examined the effect of HIT on the protein content of the transcriptional corepressor RIP140. Compared with PGC-1α, much less is known regarding the role of RIP140 in human skeletal muscle. However, animal studies have highlighted an important role for this protein in regulating oxidative metabolism and insulin sensitivity (31,37). Transgenic animal models have demonstrated that low levels promote whereas high levels inhibit the expression of genes involved in mitochondrial biogenesis, glucose transport, and lipid metabolism (31,37). Furthermore, RIP140-null mice show improved insulin sensitivity and are resistant to high-fat diet-induced obesity (31). Given the apparent contrasting roles of PGC-1α and RIP140 in controlling metabolic and mitochondrial gene networks, we hypothesized that skeletal muscle adaptations to exercise training may involve reductions in RIP140. This did not seem to be the case because total RIP140 protein was unchanged after HIT. However, this does not conclusively demonstrate that RIP140 is not involved in the adaptive response because the association of RIP140 with other proteins in nuclear receptor complexes may be the strongest determinant of its ability to repress gene expression (31).
A final novel finding from the present study was the training-induced reduction in basal Akt activation. It is important to note that muscle samples were taken in the fasted state at the same time as blood sampling. Thus, the reduction in basal Akt phosphorylation in skeletal muscle likely represents a downstream consequence of the reduction in fasting plasma insulin. Although the majority of work linking Akt to insulin resistance has been conducted in hepatic cells (22), Liu et al. (25) have recently hypothesized that basal Akt activation in skeletal muscle is linked with reduced mitochondrial content and insulin resistance. Akt has been shown to directly phosphorylate PGC-1α, leading to inhibition and degradation (22). In response to a high-fat diet, mice become insulin resistant concomitant with an increase in basal Akt activation, a reduction in PGC-1α protein, and a decrease in mitochondrial content in skeletal muscle (25). In response to 2 wk of low-volume HIT in humans, we saw an increase in insulin sensitivity, a reduction in basal Akt activation, an increase in PGC-1α protein content, and an increase in mitochondrial content in skeletal muscle. Thus, it is intriguing to speculate that the reduced basal Akt activation in skeletal muscle may be relieving inhibition or degradation of PGC-1α to promote an increase in mitochondrial biogenesis, in essence, the reverse process of what has been shown to occur in response to high-fat feeding in mice (25).
It must be acknowledged that the present findings are based on a small somewhat heterogeneous sample of inactive adult males and females. Despite this, however, we were able to detect significant changes in many muscle metabolic parameters and markers of insulin sensitivity after only 2 wk of low-volume constant-load HIT. It is possible that the differences in menstruation status could influence some of the findings in the female participants, but this was not assessed in the present study. The small sample size also limited any comparisons between males and females. On the basis of our encouraging findings for the efficacy of short-term low-volume constant-load HIT for improving markers of metabolic health, future studies should include larger sample sizes and a control group to directly assess the potential health-promoting adaptations to this type of training. Future studies should also use more direct measures of muscle insulin sensitivity and glycemic control because the assessment of insulin sensitivity using ISI (HOMA) in the present study is limited by the fact that it was based with a single fasting blood sample. Muscle glucose uptake is primarily regulated by insulin signaling to GLUT4 translocation from intracellular pools to the sarcolemma. We assessed total GLUT4 protein content in resting muscle biopsy samples in this study and as such cannot determine whether training had an influence on GLUT4 trafficking. However, an increase in total GLUT4 is a relatively rapid response and seems to be important in mediating some of the increase in muscle glucose uptake and insulin sensitivity after exercise (15,17,35).
Conclusions and significance.
In summary, the results of the present investigation demonstrate that low-volume constant-load HIT rapidly induces skeletal muscle mitochondrial biogenesis, increases GLUT4 content, and improves insulin sensitivity in previously sedentary adults. These findings provide novel information regarding the potency of low-volume HIT to improve insulin sensitivity to a similar magnitude as previous research examining higher-volume endurance training (6,30). Despite similar metabolic adaptations between this HIT and previous endurance training studies, the time requirement of the present protocol involved ∼20 min per session, totaling ∼60 min·wk−1. Given that lack of time is the most-often-cited barrier to performing regular exercise (4,42), low-volume HIT may represent an alternative to traditional endurance training to help increase exercise participation in the general population. Further research is required to examine the long-term effect of low-volume HIT on metabolic health and chronic disease prevention, but the present results suggest that low-volume HIT may be an effective exercise strategy for the prevention and treatment of insulin resistance and inactivity-related disorders.
This work was supported by the Canadian Institutes of Health and Research and the Natural Sciences and Engineering Research Council of Canada (NSERC). J.P.L. was supported by an NSERC Canada Graduate Scholarship, and F.E.M. held an NSERC Undergraduate Student Research Award.
The authors thank their subjects for their time and effort and John Moroz, Todd Prior, Dr. Krista Howarth, and Michael Percival for technical and analytical assistance.
There were no specific funding sources for this article.
The authors have no conflicts of interest to disclose.
The results of the present study do not constitute any endorsement by the American College of Sports Medicine.
1. Babraj JA, Vollaard NB, Keast C, Guppy FM, Cottrell G, Timmons JA. Extremely short duration high intensity interval training substantially improves insulin action in young healthy males. BMC Endocr Disord
2. Benton CR, Nickerson JG, Lally J, et al. Modest PGC-1α overexpression in muscle in vivo
is sufficient to increase insulin sensitivity and palmitate oxidation in subsarcolemmal, not intermyofibrillar, mitochondria. J Biol Chem
3. Blair SN, Brodney S. Effects of physical inactivity and obesity on morbidity and mortality: current evidence and research issues. Med Sci Sports Exerc
. 1999;31(11 suppl):S646-62.
4. Booth ML, Bauman A, Owen N, Gore CJ. Physical activity preferences, preferred sources of assistance, and perceived barriers to increased activity among physically inactive Australians. Prev Med
5. Bourgeois JM, Tarnopolsky MA. Pathology of skeletal muscle in mitochondrial disorders. Mitochondrion
6. Bruce CR, Trush AB, Mertz VA, et al. Endurance training in obese humans improves glucose tolerance and mitochondrial fatty acid oxidation and alters muscle lipid content. Am J Physiol Endocrinol Metab
7. Burgomaster KA, Cermak NM, Phillips SM, Benton CR, Bonen A, Gibala MJ. Divergent response of metabolite transport proteins in human skeletal muscle after sprint interval training and detraining. Am J Physiol Regul Integr Comp Physiol
8. Burgomaster KA, Howarth KR, Phillips SM, et al. Similar metabolic adaptations during exercise after low volume sprint interval training and traditional endurance training in humans. J Physiol
9. Burgomaster KA, Hughes SC, Heigenhauser GJF, Bradwell SN, Gibala MJ. Six sessions of sprint interval training increases muscle oxidative potential and cycle endurance capacity in humans. J Appl Physiol
10. Coyle EF. Very intense exercise-training is extremely potent and time efficient: a reminder. J Appl Physiol
11. Gibala MJ, Little JP, van Essen M, et al. Short-term sprint interval training versus traditional endurance training: similar initial adaptations in human skeletal muscle and exercise performance. J Physiol
12. Gibala MJ, McGee SL, Garnham AP, Howlett KF, Snow RJ, Hargreaves M. Brief intense interval exercise activates AMPK and p38 MAPK signaling and increases the expression of PGC-1α in human skeletal muscle. J Appl Physiol
13. Hawley JA. Exercise as a therapeutic intervention for the prevention and treatment of insulin resistance. Diabetes Metab Res Rev
14. Holloszy JO. Exercise-induced increase in muscle insulin sensitivity. J Appl Physiol
15. Holloszy JO. Skeletal muscle "mitochondrial deficiency" does not mediate insulin resistance. Am J Clin Nutr
16. Holloszy JO, Coyle EF. Adaptations of skeletal muscle to endurance exercise and their metabolic consequences. J Appl Physiol
17. Houmard JA, Hickey MS, Tyndall GL, Gavigan KE, Dohm GL. Seven days of exercise increase GLUT-4 protein content in human skeletal muscle. J Appl Physiol
18. Houmard JA, Tanner CJ, Slentz CA, Duscha BD, McCartney JS, Kraus WE. Effect of the volume and intensity of exercise training on insulin sensitivity. J Appl Physiol
19. Kacerovsky-Bielesz G, Chmelik M, Ling C, et al. Short-term exercise training does not stimulate skeletal muscle ATP synthesis in relatives of humans with type 2 diabetes. Diabetes
20. Koves TR, Li P, An J, et al. Peroxisome proliferator-activated receptor-gamma co-activator 1α-mediated metabolic remodeling of skeletal myocytes mimics exercise training and reverses lipid-induced mitochondrial inefficiency. J Biol Chem
21. Leick L, Wojtaszewski JFP, Johansen ST, et al. PGC-1α is not mandatory for exercise- and training-induced adaptive gene responses in mouse skeletal muscle. Am J Physiol Endocrinol Metab
22. Li X, Monks B, Ge Q, Birnbaum MJ. Akt/PKB regulates hepatic metabolism by directly inhibiting PGC-1α transcription coactivator. Nature
23. Lin J, Handschin C, Spiegelman BM. Metabolic control through the PGC-1 family of transcription coactivators. Cell Metab
24. Little JP, Safdar A, Wilkin GP, Tarnopolsky MA, Gibala MJ. A practical model of low-volume high-intensity interval training induces mitochondrial biogenesis in human skeletal muscle: potential mechanisms. J Physiol
25. Liu H, Hong T, Wen GB, et al. Increased basal level of Akt-dependent insulin signaling may be responsible for the development of insulin resistance. Am J Physiol Endocrinol Metab
26. Matsuda M, DeFronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing. Diabetes Care
27. Mootha VK, Handschin C, Arlow D, et al. Errα and Gabpa/b specify PGC-1α-dependent oxidative phosphorylation gene expression that is altered in diabetic muscle. Proc Natl Acad Sci USA
28. Morino K, Petersen KF, Shulman GI. Molecular mechanisms of insulin resistance in humans and their potential links with mitochondrial dysfunction. Diabetes
29. Morton JP, Croft L, Bartlett JD, et al. Reduced carbohydrate availability does not increase training induced stress protein adaptations but up-regulates oxidative enzyme activity in skeletal muscle. J Appl Physiol
30. O'Donovan G, Kearney EM, Nevill AM, Woolf-May K, Bird SR. The effects of 24 weeks of moderate- or high-intensity exercise on insulin resistance. Eur J Appl Physiol
31. Parker MG, Christian M, White R. The nuclear receptor co-repressor RIP140 controls the expression of metabolic gene networks. Biochem Soc Trans
32. Patti ME, Butte AJ, Crunkhorn S, et al. Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: potential role of PGC1 and NRF1. Proc Natl Acad Sci U S A
33. Petersen KF, Dufour S, Befroy D, Garcia R, Shulman GI. Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes. N Engl J Med
34. Pilegaard H, Saltin B, Neufer PD. Exercise induces transient transcriptional activation of the PGC-1α gene in human skeletal muscle. J Physiol
35. Ren J, Semenkovich C, Gulve E, Gao J, Holloszy J. Exercise induces rapid increases in GLUT4 expression, glucose transport capacity, and insulin-stimulated glycogen storage in muscle. J Biol Chem
36. Richards JC, Johnson TK, Kuzma JN, et al. Short-term sprint interval training increases insulin sensitivity in healthy adults but does not affect the thermogenic response to β-adrenergic stimulation. J Physiol
37. Seth A, Steel JH, Nichol D, et al. The transcriptional corepressor RIP140 regulates oxidative metabolism in skeletal muscle. Cell Metab
38. Sieverdes JC, Sui X, Lee D, et al. Physical activity, cardiorespiratory fitness and the incidence of type 2 diabetes in a prospective study of men. Br J Sports Med
39. Sigal RJ, Kenny GP, White RR, Wasserman DH, Castaneda C. Physical activity/exercise and type 2 diabetes: a consensus statement from the American Diabetes Association. Diabetes Care
40. Stump CS, Short KR, Bigelow ML, Schimke JM, Nair KS. Effect of insulin on human skeletal muscle mitochondrial ATP production, protein synthesis, and mRNA transcripts. Proc Natl Acad Sci U S A
41. Trapp EG, Chisholm DJ, Freund J, Boutcher SH. The effect of high-intensity intermittent exercise training on fat loss and fasting insulin levels of young women. Int J Obes (Lond)
42. Trost SG, Owen N, Bauman AE, Sallis JF, Brown W. Correlates of adults' participation in physical activity: review and update. Med Sci Sports Exerc
43. Wright DC, Han D, Garcia-Roves PM, Geiger PC, Jones TE, Holloszy JO. Exercise-induced mitochondrial biogenesis begins before the increase in muscle PGC-1α expression. J Biol Chem
Keywords:©2011The American College of Sports Medicine
EXERCISE; SKELETAL MUSCLE; PGC-1α; GLUT4; MITOCHONDRIAL BIOGENESIS