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Low-Volume Interval Training Improves
Muscle Oxidative Capacity in Sedentary Adults
MELANIE S. HOOD1, JONATHAN P. LITTLE1, MARK A. TARNOPOLSKY2, FRANK MYSLIK1,
and MARTIN J. GIBALA1
1Exercise Metabolism Research Group, Department of Kinesiology, McMaster University, Hamilton, Ontario, CANADA;
and 2Department of Pediatrics and Medicine, McMaster University, Hamilton, Ontario, CANADA
ABSTRACT
HOOD, M. S., J. P. LITTLE, M. A. TARNOPOLSKY, F. MYSLIK, and M. J. GIBALA. Low-Volume Interval Training Improves
Muscle Oxidative Capacity in Sedentary Adults. Med. Sci. Sports Exerc., Vol. 43, No. 10, pp. 1849–1856, 2011. 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 T SD age, body mass
index, and peak oxygen uptake (V̇O2peak) of 45 T 5 yr, 27 T 5 kgImj2, and 30 T 3 mLIkgj1Imin-1 performed six training sessions during
2 wk. Each session involved 10 � 1-min cycling at È60% of peak power achieved during a ramp V̇O2peak test (eliciting È80%–95% of
HR reserve) with 1 min of recovery between intervals. Needle biopsy samples (vastus lateralis) were obtained before training and È72 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 È35% after training. The transcriptional coactivator peroxisome proliferator–activated receptor F
coactivator 1> was increased by È56% after training, but the transcriptional corepressor receptor-interacting protein 140 remained
unchanged. Glucose transporter protein content increased È260%, and insulin sensitivity, on the basis of the insulin sensitivity index
homeostasis model assessment, improved byÈ35% 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. Key Words: EXERCISE, SKELETAL MUSCLE, PGC-1>, GLUT4, MITOCHONDRIAL BIOGENESIS
R
egular 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 patho-
physiology of insulin resistance is not fully understood, in-
creased 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 re-
duce 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 in-
dividuals 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 ex-
ercise 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 stud-
ies (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. [11]) and works
from other groups (1,36) have used an HIT model that in-
volves 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 na-
ture 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
Address for correspondence: Martin Joseph Gibala, Ph.D., Department of Ki-
nesiology,McMaster University, IvorWynne Centre, Room 219, 1280Main St.,
Hamilton, Ontario, Canada L8S 4K1; E-mail: gibalam@mcmaster.ca.
Submitted for publication September 2010.
Accepted for publication March 2011.
0195-9131/11/4310-1849/0
MEDICINE & SCIENCE IN SPORTS & EXERCISE�
Copyright � 2011 by the American College of Sports Medicine
DOI: 10.1249/MSS.0b013e3182199834
1849
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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 (e30 yr), and it is unclear whether
the findings can be applied to sedentary middle-aged indi-
viduals, 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 train-
ing 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 hypothe-
sized that HIT would stimulate mitochondrial biogenesis,
as evidenced by changes in the protein content of the
common marker enzymes citrate synthase (CS) and cyto-
chrome c oxidase (COX), and alter the expression of pro-
teins linked to this adaptive response including peroxisome
proliferator–activated receptor F coactivator (PGC) 1> and
receptor-interacting protein (RIP) 140 (2,23,31). A second-
ary purpose was to explore the potential clinical significance
of low-volume HIT by determining the insulin sensitiv-
ity index (ISI) using the homeostasis model assessment
(HOMA) method (26) before and after training. We hy-
pothesized 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.
METHODS
Subjects. Seven sedentary but otherwise healthy men
(n = 4) and women volunteered to participate in the study
(age = 45 T 5 yr, body mass index = 27 T 5 kgImj2, peak
oxygen uptake (V̇O2peak) = 30 T 3 mLIkgj1Iminj1). Eligi-
bility for the study was confirmed by medical screening in-
cluding the completion of a general health questionnaire and
the following measurements: height, weight, resting HR,
blood pressure, fasting plasma glucose, and an ECG. Pre-
liminary screening determinedthat participants were (a)
sedentary, defined as not having participated in a regular
exercise program (i.e., two or fewer sessions per week and
e30 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 min-
imum 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.
Preexperimental procedures. Waist circumference
was measured using a nonelastic tape at the midpoint be-
tween 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 cal-
culated (kgImj2). Resting HR and blood pressure were
measured by an automatic inflation monitor (Spot Vital
Signs�; Welch Allyn, Mississauga, Canada). Finally, rest-
ing and postexercise 12-lead ECG were conducted on the
same day as the V̇O2peak 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 V̇O2peak and peak power output (Wmax). After
a 3-min cycling warm-up at 50 W, the workload was in-
creased by 1 W every 2 s until participants reached voli-
tional exhaustion or the pedal cadence decreased to G40
revolutions per minute because power output is not valid
below this cadence according to the manufacturer’s specifi-
cations. A metabolic cart with an online gas collection sys-
tem (MOXUS Modular V̇O2 System; AEI Technologies,
Pittsburgh, PA) was used to acquire data to quantify oxy-
gen consumption, carbon dioxide production, and substrate
oxidation via RER. The coefficient of variation (CV) for
V̇O2peak measurements using the MOXUS System in our
laboratory is e4% (9). V̇O2peak 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 sam-
pling. 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 pro-
cedures. For blood sampling, subjects reported to the labo-
ratory in the morning (È8:00 a.m.) after an overnight (Q10 h)
fast. A resting blood sample was obtained by venipuncture
from an antecubital vein and treated according to man-
ufacturer’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 inci-
sion in the skin and underlying tissues. The obtained biopsy
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samples were immediately frozen in liquid nitrogen and
stored at j80-C until subsequent analysis. The final fasting
blood and muscle samples were obtained È72 h after the last
training bout using procedures identical in all respects to
preexercise baseline trials.
Experimental protocol. The training protocol was ini-
tiated at least 3 d after the pretraining muscle biopsy proce-
dure. 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 cy-
cling 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 V̇O2peak test. Mean power output during training was
È150 W, and this elicited È80% of HR reserve at the end of
the first 60-s interval, climbing to È95% 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. Par-
ticipants were instructed to continue their normal daily ac-
tivity (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, par-
ticipants recorded their dietary intake for 24 h before pre-
training sampling procedures and replicated the diet using
the same types and quantities of food before the posttraining
procedures. Subsequent dietary analyses (The Food Proces-
sor 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-1>, RIP140, phosphorylated Akt (p-Akt), and
total Akt were quantified by standard Western blotting pro-
cedures as we have previously described (10,12,24). A rab-
bit 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-1>, p-Akt, and total Akt anti-
bodies 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 Ap-
plied Science) inhibitors and protein concentration of ho-
mogenates determined using a commercial assay kit (Pierce
BCA Protein Assay Kit; Rockford, IL). The CV for protein
quantification for duplicate samples is G5.0% in our labora-
tory. Proteins were denatured by addition of 4� Laemmli
buffer and heating to 95-C for 5 min. Equal amounts of
protein (5–20 Kg) were separated by electrophoresis on
7.5%–12.5%sodium dodecyl sulfate polyacrylamide gel
electrophoresis gels for È2 h at 100 V. Proteins were elec-
trotransferred 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-1>, RIP140,
p-Akt, Akt) in 3% milk or bovine serum albumin. Membranes
were then washed for 3 � 5 min in TBS-T and incubated in-
appropriate 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 chemilu-
minescent substrate (SuperSignal� West Dura; Pierce) and
exposed to an x-ray film or visualized using a Fluorochem�
SP Imaging system and software (Alpha Innotech Corpora-
tion, San Leandro, CA). After measurement of p-Akt, mem-
branes 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 re-
sulting plasma was immediately analyzed for blood glucose
(Ascensia Contour; Bayer, Tarrytown, NY). The serum was
stored at j80-C for subsequent analysis of insulin using a
commercially available assay kit (Insulin EIA; ALPCO Di-
agnostics, Salem, NH). All samples were run in triplicate,
with the CV being G4.0% for glucose and G3.0% for insu-
lin. 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.
Statistical analyses. Differences between pre- and
posttraining values for all variables were analyzed using
paired-samples t-tests. All data are presented as mean T SD.
Significance was set at P G 0.05.
RESULTS
Skeletal muscle adaptations. The protein content of
CS and COX IV increased by 31% and 39%, respectively,
after training (P G 0.05, Fig. 1). COX II content tended to
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increase (È16%) after training, but this did not reach statis-
tical significance (P = 0.10, data not shown). Total GLUT4
content increased by È260% after training (P G 0.001,
Fig. 2). PGC-1> protein was increased by 56% after
training (P = 0.01, Fig. 3A), but there were no effects of
training on RIP140 protein content (P 9 0.05, Fig. 3B).
Basal Akt phosphorylation was reduced by È67% after
training (P G 0.05, Fig. 4), whereas total Akt protein con-
tent was not significantly different (P = 0.80).
Fasting insulin, glucose, and ISI (HOMA). Fast-
ing insulin concentration decreased by 16% after training
(after = 6.6 T 2.9 vs before = 8.1 T 3.5 KIUImLj1, P G 0.01),
whereas fasting glucose concentration was not significantly
different despite a tendency to decline (after = 4.3 T 0.5 vs
FIGURE 1—Markers of skeletal muscle mitochondrial content are in-
creased after 2 wk of HIT. CS (A) and COX IV (B) protein content
measured in resting muscle biopsy samples before (Pre) and after (Post)
training. Values are means T SD (n = 7); *P G 0.05.
FIGURE 2—Skeletal muscle GLUT4 protein content is increased af-
ter 2 wk of HIT. GLUT4 protein was measured in resting muscle bi-
opsy samples Pre and Post training. Values are means T SD (n = 7);
*P G 0.001.
FIGURE 3—Changes in transcriptional coregulators of mitochondrial
biogenesis in skeletal muscle after 2 wk of HIT. PGC-1> (A) and
RIP140 (B) protein content measured in resting muscle biopsy samples
Pre and Post training. Values are means T SD (n = 7); *P G 0.05.
FIGURE 4—Basal Akt activation is reduced after 2 wk of HIT. P-Akt
relative to total Akt (t-Akt) protein was measured in resting muscle
biopsy samples Pre and Post training. Values are means T SD (n = 7);
*P G 0.05.
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before = 4.9 T 0.3 mmolILj1, P = 0.09). As a result, insulin
sensitivity calculated by ISI (HOMA) improved after train-
ing by 35% (P G 0.05, Fig. 5).
DISCUSSION
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-1> and
RIP140, which are positive and negative regulators of mi-
tochondrial and metabolic gene expression, respectively.
PGC-1> protein increased after training, yet there were no
changes in total RIP140 content. These data support the no-
tion that low-volume constant-load HIT is a time-efficient
strategy to promote mitochondrial biogenesis and induce met-
abolic adaptations that may reduce the risk for insulin resis-
tance and T2D in previously sedentary middle-aged adults.
Low-volume HIT rapidly improves insulin sen-
sitivity. 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 re-
duce 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 hyper-
insulinemic euglycemic clamp measurements, in previously
sedentary or recreationally active young adults after an iden-
tical 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 en-
durance training (6,18,30). Although it has been suggested
that duration is more important than intensity when prescrib-
ing 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 changesin
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 im-
paired 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. [34]). Although
previous research has supported a link between improve-
ments 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 pos-
sible mechanism that improves insulin sensitivity after ex-
ercise 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 in-
crease 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 sug-
gested that reduced PGC-1> in skeletal muscle might be
implicated in the pathogenesis of insulin resistance and T2D
(25,27,32). PGC-1> coactivates several transcription factors
to coordinately upregulate a program of mitochondrial and
metabolic gene transcription in muscle (2,23). PGC-1>
mRNA expression is robustly increased in the postexercise
recovery period after endurance (34) and interval (12) ex-
ercise, and training has been shown to increase PGC-1>
protein expression in some studies (8,29). For these reasons,
PGC-1> is hypothesized to play a critical role in the mus-
cle’s adaptive response to exercise (43). Furthermore, mod-
est overexpression of PGC-1> by electrotransfection of the
PGC-1> gene into skeletal muscle of rats increases mito-
chondrial content, GLUT4 protein, and muscle insulin sen-
sitivity (2), and induction of PGC-1> can rescue cultured
muscle cells from lipotoxicity (20). Therefore, interventions
that increase PGC-1> in skeletal muscle would seem to have
beneficial effects on insulin sensitivity and metabolic health.
The increase in skeletal muscle PGC-1> protein content
FIGURE 5—Insulin sensitivity marker (ISI) HOMA is improved after
2 wk of HIT. Values are means T SD (n = 7); *P e 0.05.
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seen in the present study suggests that low-volume HIT is a
potent strategy. However, it is currently unclear whether the
increase in PGC-1> is required to direct an increase in mi-
tochondrial biogenesis and GLUT4 expression or whether
this response might play a supportive role in maintaining
such increases. Wright et al. (43) demonstrated that activa-
tion of existing PGC-1> protein that caused an increase in
nuclear abundance enabled PGC-1> 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-1>–null mice respond in a similar manner as wild-type
animals by increasing mitochondrial biogenesis after en-
durance exercise training (21). Therefore, it is likely that
PGC-1> 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-1>, 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 expres-
sion of genes involved in mitochondrial biogenesis, glu-
cose 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-1> and RIP140 in con-
trolling 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 un-
changed 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 im-
portant 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 rep-
resents a downstream consequence of the reduction in fast-
ing 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-1>, leading to inhi-
bition 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-1> 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 acti-
vation, an increase in PGC-1> protein content, and an in-
crease in mitochondrial content in skeletal muscle. Thus, it
is intriguing to speculate that the reduced basal Akt acti-
vation in skeletal muscle may be relieving inhibition or
degradation of PGC-1> to promote an increase in mito-
chondrial biogenesis, in essence, the reverse process of what
has been shown to occur in response to high-fat feeding in
mice (25).
Limitations. 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 sensi-
tivity 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 muscleinsulin 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 glu-
cose uptake is primarily regulated by insulin signaling to
GLUT4 translocation from intracellular pools to the sarco-
lemma. 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 rela-
tively 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 re-
sults 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 po-
tency of low-volume HIT to improve insulin sensitivity to
a similar magnitude as previous research examining higher-
volume endurance training (6,30). Despite similar meta-
bolic adaptations between this HIT and previous endurance
training studies, the time requirement of the present proto-
col involved È20 min per session, totaling È60 minIwkj1.
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 popu-
lation. 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
http://www.acsm-msse.org1854 Official Journal of the American College of Sports Medicine
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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 Under-
graduate 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.
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http://www.acsm-msse.org1856 Official Journal of the American College of Sports Medicine
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