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Medicine & Science in Sports & Exercise:
doi: 10.1249/MSS.0b013e3181abc1ec
Basic Sciences

Similar Expression of Oxidative Genes after Interval and Continuous Exercise

WANG, LI1,3; PSILANDER, NIKLAS1,2; TONKONOGI, MICHAIL1,4; DING, SHUZHE3; SAHLIN, KENT1,2,5

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Author Information

1GIH, the Swedish School of Sport and Health Sciences, Åstrands Laboratory, Stockholm, SWEDEN; 2Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, SWEDEN; 3Institute of Physical Education and Health, East China Normal University, Shanghai, CHINA; 4LIVI, Dalarna University, Falun, SWEDEN; and 5Institute of Sport Sciences and Clinical Biomechanics, University of Southern Denmark, Odense, DENMARK

Address for correspondence: Kent Sahlin, GIH, The Swedish School of Sport and Health Sciences, Box 5626, SE-114 86 Stockholm, Sweden; E-mail: kent.sahlin@gih.se.

Submitted for publication January 2009.

Accepted for publication April 2009.

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Abstract

Purpose: There is a debate whether interval or traditional endurance training is the most effective stimulus of mitochondrial biogenesis. Here, we compared the effects of acute interval exercise (IE) or continuous exercise (CE) on the muscle messenger RNA (mRNA) content for several genes involved in mitochondrial biogenesis and lipid metabolism.

Methods: Nine sedentary subjects cycled for 90 min with two protocols: CE (at 67% V˙O2max) and IE (12 s at 120% and 18 s at 20% of V˙O2max). The duration of exercise and work performed with CE and IE was identical. Muscle biopsies were taken before and 3 h after exercise.

Results: There were no significant differences between the two exercise protocols in the increases in V˙O2 and HR, the reduction in muscle glycogen (35%-40% with both protocols) or the changes in blood metabolites (lactate, glucose, and fatty acids). The mRNA content for major regulators of mitochondrial biogenesis [peroxisome proliferator-activated receptor (PPAR) γ coactivator 1α (PGC-1α), PGC-1-related coactivator, PPAR/δ] and of lipid metabolism [pyruvate dehydrogenase kinase isozyme 4 (PDK4)] increased after exercise, but there was no significant difference between IE and CE. However, the mRNA content for several downstream targets of PGC-1α increased significantly only after CE, and mRNA content for nuclear respiratory factor 2 was significantly higher after CE (P < 0.025 vs IE).

Conclusions: The present findings demonstrate that, when the duration of exercise and work performed is the same, IE and CE influence the transcription of genes involved in oxidative metabolism in a similar manner.

Mitochondrial density and function play pivotal roles in cell physiology and exert important influences on athletic performance and health. Repeated sessions of endurance exercise elicit profound morphological and metabolic adaptations in skeletal muscle, of which one of the most striking is a pronounced increase in the content of mitochondria. The magnitude of this latter change is dependent on the nature of the training protocol as well as the individual's training status and response to training. One difficulty inherent in training studies using classic crossover design is the increase in training status evoked by the first training period. It would be of considerable value if early indicators of training-induced signaling could be identified and used to evaluate different protocols. Recent studies have demonstrated that even a single session of exercise can induce changes in the transcription of genes, whose products are involved in the early stages of mitochondrial biogenesis (14). This may provide the possibility to assess the efficiency of a training protocol after only one exercise bout.

The complex process of mitochondrial biogenesis involves the expression of a large number of genes encoded by both the nuclear and mitochondrial genome, and the molecular mechanisms underlying this coordinated expression in muscle cells remain to be clarified (9). Peroxisome proliferator-activated receptor (PPAR) γ coactivator 1α (PGC-1α) acts as a "master regulator" of mitochondrial biogenesis in skeletal muscle, apparently via coactivation of numerous mitochondrial transcription factors including the nuclear respiratory factors (NRF-1 and NRF-2) and mitochondrial transcription factor A (Tfam) (10,31). Exercise can enhance transcription of the PGC-1α gene in skeletal muscle through adenosine monophosphate (AMP)-activated protein kinase (AMPK) and/or Ca2+-induced activation of the calcineurin or calmodulin signaling pathways (10,32). AMPK, a cellular energy sensor of the cell, is activated when the concentration of AMP increases as a result of rapid utilization of adenosine triphosphate (ATP). Activation of AMPK leads to phosphorylation of PGC-1α (10) and increased binding to responsive elements in the promoter region of various genes. The other two known members of the PGC-1 family, i.e., PGC-1 and PGC-1-related coactivator (PRC), play similar roles in mitochondrial biogenesis as indicated by their ability to coactivate NRF-1, NRF-2, and isoforms of the PPARs (13,25).

Adaptations of muscle are dependent on the frequency, intensity, duration, and mode of exercise in a highly specific manner. At present, there is a controversy over whether interval exercise (IE) or traditional continuous exercise (CE) is the most effective stimulus of mitochondrial biogenesis. CE is characterized by prolonged exercise at a constant submaximal intensity, whereas IE involves alternating periods of high- and low-intensity exercise. Several studies have shown that training at moderate intensity for a prolonged period is effective in enhancing the overall capacity to transport and use oxygen and in inducing mitochondrial biogenesis. In contrast, IE training has traditionally been considered to stimulate anaerobic to a greater extent than aerobic capacity (4). However, a growing body of evidence indicates that, under certain conditions, IE can be more effective than CE in stimulating the oxidative potential. For instance, in one study, where the total energy expenditure and duration of training for CE and IE were matched, muscular oxidative capacity increased only after IE training (2). Because of the inclusion of periods with high-intensity exercise, it seems likely that energy stress and metabolic perturbation are more severe during IE than during CE. This should cause more pronounced activation of AMPK and, thus, more rapid transcription of the PGC-1α gene. Other factors that might induce a stronger response to IE include the more extensive recruitment of fast-twitch Type II fibers and the more pronounced fluctuation of O2 tension in the working muscles. The higher level of PGC-1α messenger RNA (mRNA) observed after hypoxic than after normoxic training, performed at the same absolute work rate, is consistent with the proposal that energy stress is an important determinant of the training response (18). Furthermore, 2 wk of IE training involving short bursts of maximal exercise has been reported to improve muscle oxidative capacity and endurance to the same extent as CE training despite a considerable lower exercise duration and training volume during IE (5). IE training may thus represent a time-efficient strategy for achieving adaptations normally associated with endurance training (2,4,5,22).

Although several studies have compared the effects of CE and IE on metabolic adaptation (2,5), to the best of our knowledge, there is no report on the acute transcriptional regulation of oxidative genes by CE and IE. Accordingly, the purpose of the present investigation was to compare the transcription of genes related to mitochondrial biogenesis and oxidative lipid metabolism after a single bout of CE or IE of the same duration and amount of work performed. In light of the expected higher levels of energy stress and recruitment of Type II fibers concerning IE, we hypothesized that this type of training more potently enhances the transcription of genes associated with mitochondrial biogenesis and oxidative lipid metabolism.

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MATERIALS AND METHODS

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Subjects.

Nine healthy sedentary subjects (seven men and two women) participated in the present study. The average age, height, weight, and V˙O2max were 26.3 ± 1.3 yr, 174.1 ± 3.3 cm, 72.3 ± 4.5 kg and 40.9 ± 2.2 mL·kg−1·min−1, respectively. Subjects were sedentary and participated in vigorous physical activity less than 2 h·wk−1 during the 6-month period before this study. After being informed about the possible risks and discomforts involved in the experiment, subjects gave their written consent before participation. The design of the study was approved by the Regional Ethics Committee of Stockholm, Sweden (No. 2007/464).

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Determination of maximal oxygen uptake (V˙O2max).

V˙O2max was determined at least 3 d before the main experiment using a standardized exercise test on a cycle (Monark Ergomedic 893E; Monark Exercise, Varberg, Sweden) with proper adjustment of the seat and handlebar height to fit each subject and subsequent maintenance of these during the experimental sessions. After a 5-min warm-up period (60 rpm, 30-50 W), the power output was increased at a rate of 30-40 W every 3 min until the subject attained a rating of 17-18 on the Borg scale. After a 3-min rest, each subject repeated this test with a more rapid increase in the power output until the subject felt exhausted. Throughout this procedure, respiratory parameters (V˙O2, V˙CO2, RER, and ventilation) were monitored continuously with an online system (AMIS 2001; Inovision A/S Odense, Denmark) and the HR recorded using a HR monitor (Polar Electro Oy, Kempele, Finland) interfaced with the computer. The RPE was rated according to the Borg category (6-20 scale). Each participant achieved at least two of the following criteria for V˙O2max, i.e., an RPE ≥ 18, an RER ≥ 1.1, a plateau of V˙O2 with increased workload, and/or an HR >85% of the age-predicted maximum. The average of the highest values of V˙O2 recorded during two or three 15-s intervals was taken to be the V˙O2max.

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Experimental design and exercise protocol.

Each subject participated in two experimental sessions (in randomized order) separated by an interval of at least 2 wk for men and 4 wk in the case of the women (to minimize the possible influence of the menstrual cycle; Fig. 1). In one of these sessions, the subject cycled for 90 min at a constant work rate corresponding to 60% of V˙O2max (CE) and in the other session he/she performed IE involving cycling alternately for 12 s at 120% of V˙O2max and for 18 s at 20% of V˙O2max. The work rate during the second exercise session was adjusted to match the duration and the total work performed during the first session. The participants were instructed to eat normally but to refrain from the consumption of alcohol, caffeine, and tea during the 24-h period preceding the test and not to do any strenuous exercise for 48 h before the tests. On the day of testing, the subject arrived at the laboratory in the morning, after fasting overnight. After a 5-min warm-up period at 25% of V˙O2max, each subject cycled for 90 min according to the CE or IE protocol, at a stable speed of about 60 rpm. A 3-min break was allowed after 30 and 60 min of work. Each subject drank a cup of juice 5 min before beginning to cycle and had access to water ad libitum, but no food during the exercise and recovering periods. Respiratory parameters, HR, and RPE were determined before the exercise (after the warm-up) and after 30, 60, and 90 min of cycling. The volume of expired air was determined using the Douglas bag technique with a Tissot Spirometer (WE Collins, Braintree, MA), and the contents of O2 and CO2 were analyzed using a Beckman s-3A and LB2 gas analyzer (Beckman Instruments, Fullerton, CA). Venous blood samples were drawn before exercise, after 15-min rest in a supine position (designated Pre), during the final minutes of exercise (Post), and 3 h after completion of cycling (3 h Post). Muscle biopsies were taken before beginning the exercise (Pre; leg 1), immediately after completion (Post; leg 2) and 3 h later (3 h Post; leg 1). The time that elapsed from the completion of exercise to taking the third biopsy varied between 186 and 207 min between the subjects but was kept the same for the CE and IE sessions performed by each subject. The leg (right or left) used for the first biopsy was determined randomly for each subject, and biopsy of the opposite leg was performed first in the second session. The values of the biopsy taken immediately after exercise are not presented because the glycogen content in this sample was much lower than that in the biopsy taken 3 h later, suggesting that the leg from which the postexercise biopsy was taken (no preexercise biopsy) had performed more work than the other leg. Because of this confounding factor as well as inconsistent changes in the level of mRNA, we have excluded all of the data obtained on this Post muscle sample.

FIGURE 1-A schematic...
FIGURE 1-A schematic...
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Blood analysis.

Blood samples (4 mL) were centrifuged at 1500g at 4°C for 10 min, and the plasma thus obtained was stored at −20°C for later analysis of free fatty acids (FFA) with commercially available colorimetric enzymatic procedure (NEFA C test kit; Wako Chemicals GmbH, Neuss, Germany). Glucose and lactate were measured in whole blood using an automated glucose/lactate analyzer (EKF-diagnostic GmbH, Germany).

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Muscle biopsies.

Muscle samples were taken with a Bergström percutaneous needle (modified for suction) from the middle portion of the vastus lateralis muscle. Under local anesthesia (2-3 mL of Carbocain, 20 mg·mL−1; Astra-Zeneca, Södertälje, Sweden) through an incision made through the skin and fascia at one-third the distance between the patella and anterior superior iliac spine. These muscle samples was frozen rapidly in liquid nitrogen and stored at −80°C for later determination of mRNA levels and glycogen content.

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Determination of glycogen content.

The muscle samples were freeze-dried and dissected free from blood, connective tissue, and adipose tissue. Thereafter, the glycogen content in 1-2 mg of [dry weight (dw)] muscle was determined according to the method described by Leighton et al. (12), which includes acid hydrolysis of glycogen followed by enzymatic analysis of glucose.

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RNA extraction and real-time polymerase chain reaction.

Total RNA was extracted from 2 to 5 mg of freeze-dried muscle tissue by homogenization with a glass homogenizer in PureZOL RNA Isolation Reagent (Bio-Rad Laboratoies AB, Sundbyberg, Sweden) according to the instruction manual. Spectrometry was used to assess the concentration and the purity of the isolated RNA. One microgram of RNA was used to produce 20 μL of complementary DNA (cDNA) with iScript cDNA Synthesis Kit (Bio-Rad Laboratories AB, Sundbyberg, Sweden). The specific genes analyzed and the primers used for this analysis are presented in Table 1. The concentration of cDNA, annealing temperature, and polymerase chain reaction (PCR) procedure were optimized for each primer pair and were within the linear range for PCR amplification. Control (Pre) and experimental samples (3 h Post) were run in parallel on the same plate to permit direct comparisons of their relative levels. Real-time PCR amplification was performed with a Bio-Rad iCycler (Bio-Rad Laboratories) in mixtures (25 μL) containing 12.5 μL of 2× SYBR Green Supermix (Bio-Rad Laboratories), 0.5 μL of both the forward and reverse primers (final concentrations, 10 μM), and 11.5 μL of template cDNA. As references, the levels β-actin, cyclophilin, and glyceraldehydephosphate dehydrogenase (GAPDH) mRNA were analyzed. But because these levels for β-actin and cyclophilin tended to increase after exercise, GAPDH mRNA was used as the sole reference for quantification of mRNA levels. Relative changes in mRNA levels were analyzed with the Normalized Expression Vandesompele method (CT Advanced).

Table 1
Table 1
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Statistics.

The data are presented as means ± SE. Changes in the levels of FFA, glucose, and lactate with time were evaluated with one-way repeated-measures ANOVA, followed by Student-Newman-Keul's post hoc test. Changes in muscle content of glycogen were analyzed for statistical significance with the paired t-test. In most cases, mRNA levels were not normally distributed, so changes in these levels were examined using the nonparametric Wilcoxon signed rank test. Spearman's correlation test was used to analyze the correlations between variables. The threshold for significance was set at P < 0.05 or when the same values were used twice, P < 0.025.

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RESULTS

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Physiological and metabolic responses to exercise.

All subjects completed two 90-min sessions of cycling. The average work rate was 123 ± 11 W (corresponding to 59 ± 1.2% of V˙O2max) during CE. During IE, the work rate alternated between 243 ± 22 W (118 ± 2% of V˙O2max) and 41 ± 4.2 W (20 ± 0.4% of V˙O2max), but the average work rate (121 ± 10 W) was not different from that during CE. V˙O2 increased approximately six-fold during both CE and IE (Table 2) and corresponded to 67 ± 2% and 66 ± 2% of V˙O2max, respectively. HR and RPE increased during both forms of exercise and demonstrated a tendency to be elevated at the end of the exercise period.

Table 2
Table 2
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The muscle glycogen content decreased from 476 ± 29 to 312 ± 36 mmol·kg−1 dw during CE (a 35 ± 6% reduction) and from 485 ± 29 to 291 ± 34 mmol·kg−1 dw (a 40 ± 6% reduction) during IE (P < 0.01 in both cases; P > 0.05 for IE in comparison to CE). Blood lactate levels were elevated significantly after both forms of exercise (P < 0.01; Table 3) but nonetheless remained low (<5 mmol·L−1) in all subjects. In addition, blood glucose levels decreased significantly after both forms of exercise (P < 0.05) and remained depressed for at least 3 h, whereas FFA levels increased significantly and remained elevated during the 3-h recovery period (P < 0.01). All of the physiological and metabolic parameters monitored here were highly similar concerning CE and IE.

Table 3
Table 3
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Expression of genes in PGC-1 family.

Gene expression of the members of PGC-1 family (PGC-1α, PGC-1β, and PRC) was affected differently by exercise. Whereas the level of PGC-1α mRNA was elevated by 10- and 13-fold 3 h after CE and IE, respectively (P < 0.025), the level of PRC mRNA increased 6-fold (P < 0.025), and the level of PGC-1β mRNA did not change significantly (Fig. 2A). However, the changes in the level of PGC-1α mRNA were positively correlated to those in PGC-1β mRNA (r = 0.65, P = 0.058 and r = 0.82, P = 0.007 in the case of CE and IE, respectively) but not to PRC (Figs. 3A and B). There were no differences between CE and IE with respect to the levels of these three species of mRNA. Furthermore, analysis of each individual subject revealed neither a correlation between the changes in these levels and the changes in physiological (HR, RPE) or metabolic parameters (V˙O2, glycogen depletion, blood metabolites) nor a correlation with the maximal aerobic capacity (V˙O2max).

FIGURE 2-Exercise-in...
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FIGURE 3-Correlation...
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Transcription of upstream and downstream genes of PGC-1α.

AMPK is an upstream activator of PGC-1α and the level of AMPKα1 mRNA was significantly elevated after CE (P < 0.025) but not after IE (Table 4). In contrast, the level of AMPKα2 mRNA was not altered in either case. Of the three members of PPAR family, the level of PPARβ/δ mRNA was enhanced significantly after both CE and IE (P < 0.025), but mRNA of PPARα and PPARγ was not altered. The level of mRNA species encoding several proteins downstream of PGC-1α (i.e., NRF-2, Tfam, TFB1M, and TFB2M) were increased significantly after CE [increases: NRF-2, 1.7-fold (P < 0.025); Tfam, 2.1-fold (P < 0.025); TFB1M, 1.7-fold (P = 0.038); and TFB2M, 2.8-fold (P < 0.025)] but not after IE (Fig. 2B).

Table 4
Table 4
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Lipoprotein lipase (LPL), pyruvate dehydrogenase kinase (PDK), and carnitine palmitoyltransferase 1 (CPT-1) are all involved in lipid metabolism. The level of pyruvate dehydrogenase kinase isozyme 4 (PDK4) mRNA exhibited a pronounced increase after both types of exercise (P < 0.025). One subject had an extremely large increase in PDK4 mRNA (145-fold) after CE, whereas the other subjects demonstrated similar increases after CE and IE. The level of LPL mRNA increased 2-fold (P < 0.025) after CE but was unaltered by IE. CPT-1β mRNA was unaffected by either type of training.

Statistical analysis revealed that the level of NRF-2 mRNA was significantly higher after CE than after IE (P < 0.025; Table 4). The exercise-induced expression of all other genes was not significantly different between the two forms of exercise.

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Correlations between alterations in mRNA levels.

In addition to the positive correlation between the changes in the levels of PGC-1α and PGC-1β mRNA (Fig. 3A), the change in the level of NRF-2 mRNA was positively correlated to the alterations in NRF-1, Tfam, TFB1M, and TFB2M mRNA (Figs. 3C-F). All these correlations were significant for both CE and IE.

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DISCUSSION

To our knowledge, this is the first study to compare the changes in the expression of genes related to mitochondrial biogenesis during acute IE and CE. Because the total amount of work performed and the duration of CE and IE were identical, any difference observed could be attributed to the form of exercise. The level of mRNA encoding the master regulator (PGC-1α) as well as other major regulators of mitochondrial biogenesis (PRC and PPARβ/δ) was elevated significantly after both forms of exercise, with the only difference being a significant higher level of NRF-2 mRNA after CE.

Accordingly, our hypothesis that IE is a more powerful stimulus of mitochondrial biogenesis than CE is not supported by the findings documented here. One consideration on which our hypothesis was based is that IE, which includes periods of high-intensity exercise (120% V˙O2max), should result in a more pronounced energetic stress than moderate-intensity exercise performed at a constant rate of work (CE). Higher energetic stress is associated with a more pronounced increase in AMP/ATP ratio and activation of AMPK and, thus, of mitochondrial biogenesis. Energetic stress also leads to increased lactate formation, which in cell cultures have been shown to stimulate the transcription of several genes, including genes involved in mitochondrial biogenesis (7). However, the metabolic parameters monitored here in the blood (lactate, glucose, and FFA) and muscle (glycogen) were altered in a similar manner concerning CE and IE, indicating a similar overall degree of metabolic perturbation. Possibly, periods of high-intensity exercise longer than that used in the present study (12 s) would stimulate mitochondrial biogenesis more effectively because of more extensive anaerobic production of energy.

It is likely that the two forms of exercise result in different patterns of fiber recruitment, with more pronounced activation of fast-twitch Type II fibers during IE. The expression of several genes associated with mitochondrial biogenesis in muscle differs between fiber types and exercise may thus elicit fiber-type-specific coordinated induction of their expression (23). For example, on examining the level of mitochondrial cytochrome C in different rat muscles after training at different intensities and durations, Dudley et al. (3) found that, whereas oxidative muscle (i.e., slow-twitch and fast-twitch red) fibers demonstrated maximal expression of this protein after moderate-intensity (60%-83% V˙O2max) exercise, higher-intensity exercise (>90% V˙O2max) was required to elicit an elevation in the cytochrome C content of fast-twitch white fibers. Because mRNA levels were measured here in samples containing a mixture of muscle fibers, we do not know whether the two types of exercise evoked different responses in the two different types of fibers. Recent technological advancements allowing measurement of mRNA in single fiber (28) should resolve this issue soon.

Another possible explanation for the similar responses in gene transcription after IE and CE could be that our subjects were all sedentary, with a relatively low V˙O2max. In such individuals, even exercise at a moderate intensity (67% of V˙O2max) might be sufficient to elicit maximal changes in gene transcription, and it cannot be excluded that endurance-trained subjects would elicit a more pronounced response during IE than during CE.

The levels of PGC-1α mRNA and protein in both human and rat muscles have been reported previously to increase after a single bout of exercise (14,18,21,26,27,29). In the present investigation, the level of PGC-1α mRNA was elevated 10- to 13-fold 3 h after 90 min of exercise, a response similar to the 7- to 12-fold increase observed in certain other studies on humans 3 h after prolonged exercise (21,29) but more pronounced than that detected after short-term IE (a 2-fold increase 3 h after four bouts of 30-s cycling at maximal capacity) (6). Recently, Burgomaster et al. (1) found that the enhancements in the level of PGC-1α protein and in the activities of oxidative enzymes after sprint interval training (six bouts of 30-s cycling at maximal capacity) and endurance training (60 min of cycling at 65% V˙O2max) were similar. Thus, short bursts of intense exercise repeated four to six times can improve muscle oxidative capacity to the same extent as traditional endurance training and may be a more time-efficient form of training (2,4,5,22).

Furthermore, the present observations of unchanged level of PGC-1β mRNA along with an increased level of PRC mRNA after exercise are consistent with previous studies (15,16,24). The pronounced induction of PGC-1α and PRC mRNA and lack of change in PGC-1β mRNA indicates that transcription of the three corresponding genes is influenced differently by exercise. At the same time, the positive correlation observed between the levels of PGC-1α and PGC-1β mRNA indicates that the expression of these two genes is regulated coordinately after execise, although the magnitudes of change differ vastly.

Several findings suggest that activation of PPARβ/δ and/or PPARα is involved in regulating expression of the PDK4 gene (11,17). In addition, exercise-induced activation of the expression of PGC-1α seems to enhance PDK4 gene expression independently of these two nuclear receptors (30). PDK inhibits the conversion of pyruvate to acetyl-CoA by phosphorylating and thereby inactivating the pyruvate dehydrogenase complex. The dramatic induction of PDK4 mRNA observed here, as well as in previous work on humans (8,19,20), may be important for conserving carbohydrates during prolonged exercise and for replenishing glycogen levels during the recovery period. The increased expression of LPL, an enzyme involved in the utilization of circulating lipids, may serve a similar purpose.

The findings documented here reveal that the expression of genes encoding upstream (AMPKα1, PGC-1α, PRC, and PPARβ/δ) and downstream (NRF-2, Tfam, TFB1M, TFB2M, and PDK4), regulators of mitochondrial biogenesis, is altered rapidly after acute exercise. However, the levels of mRNA encoding certain other proteins involved in this same process (AMPKα2, NRF-1, CPT-1β, etc.) were unchanged after exercise, in agreement with previous studies (27). Perhaps activation of the transcription of these genes requires exercise of longer duration or a larger number of training sessions and/or posttranscriptional events may be more important for these proteins.

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Summary and future research directions.

The present investigation provides a general profile of the transcriptional regulation of a series of genes involved in mitochondrial biogenesis during exercise. Continuous and interval cycling exercise of the same duration and involving the same total amount of work were found to result in similar metabolic responses, as well as similar increases in the levels of mRNA encoding several major regulators of mitochondrial biogenesis (i.e., PGC-1α, PRC, and PPARβ/δ) and of metabolism (PDK4). The levels of mRNA encoding several downstream signaling components (i.e., NRF-2, Tfam, TFB1M, and TFB2M) were enhanced significantly after CE but not after IE. However, only the level of NRF-2 mRNA was influenced differently by CE and IE. Furthermore, the positive correlations between changes in the levels of PGC-1α and PGC-1β mRNA and of mRNA species encoding for their downstream targets (NRF-1, NRF-2, Tfam, TFB1M, and TFB2M) suggest coordinate regulation of the corresponding genes concerning acute exercise. Thus, our present findings demonstrate that exercise involving short bursts of high-intensity exercise evokes alterations in the levels of mRNA encoding proteins associated with mitochondria biogenesis similar to those resulting from CE at a constant submaximal work rate. However, possibly, the degree of metabolic perturbation (i.e., the extent to which the AMP/ATP rate and circulating levels of lactate are increased) is an important determinant of oxidative adaptation to training and that schedules of interval training other than that used here would be more effective.

This work was supported financially by grants from the Swedish Research Council (project 20654), the Swedish National Centre for Research in Sport, the Swedish School of Sport and Health Sciences (GIH), and the Chinese PhD Program Scholarship Fund of ECNU 2007. This investigation has not received funding from the National Institutes of Health, Wellcome Trust, Howard Hughes Medical Institute, or other research funding agencies with accessibility requirements. The results of the present study do not constitute endorsement by the American College of Sports and Medicine. The authors thank all of the participants and Sofia Grünerwald Hägglund for her helpful assistance. None of the authors had any potential financial conflicts of interest.

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Keywords:

BIOMARKERS; INTERVAL TRAINING; METABOLIC ADAPTATION; MUSCLE OXIDATIVE POTENTIAL; TRANSCRIPTIONAL REGULATION

©2009The American College of Sports Medicine

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