Content uploaded by Sonia M Najjar
Author content
All content in this area was uploaded by Sonia M Najjar on Jun 20, 2015
Content may be subject to copyright.
Clinical Science (2008) 115,283–293(PrintedinGreatBritain) doi:10.1042/CS20070332 283
Both aerobic endurance and strength
training programmes improve cardiovascular
health in obese adults
Inga E. SCHJERVE
∗
, Gjertrud A. TYLDUM
∗
, Arnt E. TJØNNA
∗
,TomasSTØLEN
∗
,
Jan P. LOENNECHEN†, Harald E. M. HANSEN
∗
,PerM.HARAM‡,
Garreth HEINRICH§,AnjaBYE
∗
,SoniaM.NAJJAR§, Godfrey L. SMITH
∗
∥,
Stig A. SLØRDAHL
∗
†, Ole J. KEMI∥ and Ulrik WISLØFF
∗
†
∗
Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway,
†Department of Cardiology, St. Olav’s Hospital, Trondheim, Norway, ‡Department of Cardiothoracic and Vascular Surgery,
University Hospital North Norway, Tromsø, Norway, §Department of Physiology, Pharmacology, Metabolism and Cardiovascular
Sciences, Medical University of Ohio, Toledo, OH, U.S.A., and ∥Institute of Biomedical and Life Sciences, University of
Glasgow, Glasgow, U.K.
ABSTRACT
Regular exercise training is recognized as a powerful tool to improve work capacity, endothelial
function and the cardiovascular risk profile in obesity, but it is unknown which of high-intensity
aerobic exercise, moderate-intensity aerobic exercise or strength training is the optimal mode of
exercise. In the present study, a total of 40 subjects were randomized to high-intensity interval
aerobic training, continuous moderate-intensity aerobic training or maximal strength training
programmes for 12 weeks, three times/week. The high-intensity group performed aerobic
interval walking/running at 85–95 % of maximal heart rate, whereas the moderate-intensity
group exercised continuously at 60–70 % of maximal heart rate; protocols were isocaloric.
The strength training group performed ‘high-intensity’ leg press, abdominal and back strength
training. Maximal oxygen uptake and endothelial function improved in all groups; the greatest
improvement was observed after high-intensity training, and an equal improvement was observed
after moderate-intensity aerobic training and strength training. High-intensity aerobic training
and strength training were associated with increased PGC-1α (peroxisome-proliferator-activated
receptor γ co-activator 1α) levels and improved Ca
2+
transport in the skeletal muscle, whereas
only strength training improved antioxidant status. Both strength training and moderate-intensity
aerobic training decreased oxidized LDL (low-density lipoprotein) levels. Only aerobic training
decreased body weight and diastolic blood pressure. In conclusion, high-intensity aerobic interval
training was better than moderate-intensity aerobic training in improving aerobic work capa-
city and endothelial function. An important contribution towards improved aerobic work capacity,
endothelial function and cardiovascular health originates from strength training, which may serve
as a substitute when whole-body aerobic exercise is contra-indicated or difficult to perform.
Key words: calcium transport, cardiovascular health, endothelial function, exercise training, obesity.
Abbreviations: 1RM, one repetition maximum; ABTS, 2,2
′
-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid); BMI, body mass
index; BP, blood pressure; CRP, C-reactive protein; DBP, diastolic BP; FMD, flow-mediated dilation; HbA
1c
,glycatedhaemoglobin;
HDL, high-density lipoprotein; HR, heart rate; HR
max
,maximalHR;LDL,low-densitylipoprotein;NTG,nitroglycerine;PGC-
1α,peroxisome-proliferator-activatedreceptorγ co-activator 1α;RER,respiratoryexchangeratio;RPE,rateofperceivedexertion;
SERCA, sarcoplasmic/endoplasmic reticulum Ca
2+
ATPase;
˙
Vo
2max
,maximaloxygenuptake.
Correspondence: Dr Ulrik Wisløff (email ulrik.wisloff@ntnu.no).
C
⃝
The Authors Journal compilation
C
⃝
2008 Biochemical Society
284 I. E. Schjerve and others
INTRODUCTION
The global epidemic of overweight and obesity has
become a major health, social and economical burden
with 312 million people worldwide being obese [BMI
(body mass index) ! 30 kg/m
2
] and at least 1.1 billion
people being overweight (BMI 25–29.9 kg/m
2
) [1,2].
It has now been well established that obesity directly
increases cardiometabolic risk by altering the secretion
of adipokines and, indirectly, by promoting insulin
resistance and its associated metabolic disorders, such
as Type 2 diabetes. Moreover, obesity causes additional
health problems as it is closely associated with the
development and progression of coronary heart disease,
certain forms of cancer, respiratory complications (e.g.
obstructive sleep apnoea) and osteoarthritis [3]. Both
overweight and obesity appear to be associated with
low aerobic capacity and impaired endothelial function
[4], of which both serve as strong and independent ri sk
factors of mortality from cardiovascular and metabolic
diseases [5–7]. Endurance training improves both aerobic
capacity [8,9] and endothelial function [9,10], and is
now increasingly recommended in the prevention and
treatment of overweight and obesity [11].
Cardiovascular risk profiling attempts to establish the
absence or presence of a number of risk factors that,
together with overweight and obesity, contribute to the
progression of cardiovascular disease, such as endothelial
dysfunction, hypertension, inactivity and poor exercise
capacity. Moreover, a number of well-established blood
markers, such as cholesterol, triacylglycerols (trigly-
cerides), creatinine, glucose and insulin resistance, are also
used to complement the risk assessment. In general, exer-
cise, in particular endurance exercise training, decreases
cardiovascular risk, but an optimal training programme
has not yet been identified. Similarly, criteria for the min-
imum protective exercise programme against overweight
and obesity have not been established. Although the
recommended exercise intensity spans the range 40–90%
of
˙
Vo
2max
(maximal oxygen uptake), most studies indicate
that high-intensity exercise, i.e. toward the upper end of
the range, results in larger aerobic and cardiovascular ad-
aptations [8,12–14], and many rehabilitation programmes
advocate the use of low-to-moderate-intensit y exercise.
Exercise training at an intensity of approx. 90 % of
˙
Vo
2max
is in the upper range of current guidelines for humans
[11,15], and yields larger improvements in
˙
Vo
2max
than
moderate-intensity exercise [8,9,16].
Although high-intensity exercise results in a lower
percentage of fat oxidation during the exercise sessions,
it is important to highlight that it is the total amount
of fat oxidized that determines weight loss. In line with
this, isocaloric training programmes at 45 and 85% of
˙
Vo
2max
caused the same reductions in body fat and weight
despite more fat (in percentage) being oxidized in the
low-intensity group during the exercise sessions [17].
This is explained by the continued fat oxidation during
the restitution phase; the higher the intensity of the
exercise, the higher the fat oxidation post-exercise [18,19].
Interestingly, it has also been found that the resting meta-
bolism is higher after strength t raining than endurance
training with low or moderate intensity [19], but it is not
known whether high-intensity endurance training yields
the same effect on basal metabolism as strength training.
Furthermore, little is known about the impact of strength
training on cardiovascular health benefits and endothelial
function compared with endurance training regimes,
which have been found to improve the cardiovascular
risk profile, including endothelial function [9].
Therefore the aim of the present study was to
determine the efficiency of high-intensity aerobic train-
ing, moderate-intensity aerobic training and strength
training in improving cardiovascular health in obese
individuals.
MATERIALS AND METHODS
Subjects
Atotalof40subjectsvolunteeredforthepresentstudy
and underwent a thorough medical examination before
inclusion. Inclusion criteria were males and females
>20 years of age and who had a BMI >30 kg/m
2
.Exclu-
sion criteria were unstable angina pectoris, myocardial
infarction within the last 12 months, decompensated
heart failure, cardiomyopathy, severe valvular heart dis-
ease, considerable pulmonary disease, uncontrolled
hypertension, kidney failure, orthopaedic and/or neuro-
logical limitations to exercise, surgery during the
intervention period, drug or alcohol abuse, or partici-
pation in another research study. A compliance with the
training programme of 70 % was also set as a criterion
for completing the study.
The protocol was approved by the regional Ethical
Committee for Medical Research, and the study
conformed to the Declaration of Helsinki. Written
informed consent was obtained from all subjects prior to
inclusion in the study. For each individual, all pre- and
post-tests were performed at the same time of the day.
Study design
The subjects were randomized to strength training
(n = 13), continuous moderate-intensity aerobic train-
ing (n = 13) or high-intensity aerobic interval training
(n = 14). Participants in all of the groups were encouraged
to continue their normal nutritional habits during the
study period. The procedures to make sure that the exer-
cise programmes were as equal as possible with regard
to energy expenditure have been described previously in
detail by our group [8].
Over a 12-week period, the subjects performed three
programmed exercise sessions per week; two supervised
C
⃝
The Authors Journal compilation
C
⃝
2008 Biochemical Society
Effect of training programmes on cardiovascular health in obese adults 285
by the study investigators in the research laboratory
and one performed at home or in a gym, according to
instructions. All tests and measurements described below
were performed before (pre) and after (post) the training
period.
Aerobic training
Exercise training in both the high-intensity and
moderate-intensity groups was by treadmill walking or
running. High-intensity training consisted of a 10 min
warm-up period at 50–60 % of HR
max
[maximal HR
(heart rate)], followed by 4×4-min intervals at 85–95 %
of HR
max
with 3 min active breaks in between the
intervals, consisting of walking or jogging at 50–60%
of HR
max
.Theexercisesessionwasterminatedbya
5mincool-downperiod.Themoderate-intensitygroup
walked continuously for 47 min at 60–70 % of HR
max
to ensure that the training protocols were isocaloric [8].
The subjects were instructed to control the intensity
of the exercise by monitoring their HR and thereby
adjusting the speed and/or incline of the treadmill
to correspond to the preferred exercise intensity. For
each session, HR, speed and incline were recorded.
Participants were instructed to do the home training as
outdoor uphill walking, in line with the laboratory-based
training programme. The subjects were also instructed
to register the intensity during their home sessions using
the Borg RPE (rate of perceived exertion) 6–20 scale,
whereby interval training should correspond to 16–18
and moderate training to 12–14 [9].
Strength training
The basis for the development of muscular strength
is muscular hypertrophy and neural adaptations [20].
Before carrying out high-intensity strength training, sub-
jects warmed up by treadmill walking for 15 min at 40–
50% of HR
max
.Inthepresentstudy,wechoseastrength
training regime of four series with five repetitions each,
at approx. 90 % of 1RM (one repetition maximum), in a
leg press apparatus to develop maximal strength mainly
from neural adaptation with minimal weight gain due
to muscular hypertrophy [20–22]. In addition, during
each strength training session, the subjects performed
additional abdominal and back exercises, consisting
of three series of 30 repetitions with a 30 s break in
between each series. At home or in the gym, the subjects
warmed-up by walking and performed the abdominal
and back strength programme on the floor and the leg
strength programme in a leg press apparatus or as squats
with appropriately loaded backpacks.
Endothelial function
Endothelial function was measured as FMD (flow-
mediated dilation) using high-resolution vascular ultra-
sound (14 MHz echo Doppler probe; Vivid 7 System; GE
Vingmed Ultrasound) according to the current guidelines
[23,24]. The measurements were done on the brachial
artery approx. 4.5 cm above the antecubital fossa. All
measurements were performed in the morning after an
8-h fast. In addition, subjects were not allowed to use
nicotine and coffee, or any other caffeine-containing
beverages, for 12 h preceding testing. After a rest of
10 min in the supine position in a quiet air-conditioned
room with a stable temperature of 22
+
−
1
◦
C, the internal
diameter of the brachial artery was assessed. Thereafter
we inflated a pneumatic cuff (Hokanson SC10) on
the upper arm to 250 mmHg for 5 min and deflated
it to create an ischaemia-induced hyperaemic-elevated
blood flow. Data were recorded 10 s after cuff release
to measure peak blood flow, whereas artery diameter
was recorded every 30 s for 5 min. The subjects then
rested for 5 min until the baseline diameter was restored.
Subsequently, endothelium-independent dilation was
measured by administrating 500 µgofNTG(nitroglycer-
ine) sublingually. To avoid confounding effects of arterial
compliance and cyclic changes in arterial dimension, all
measurements were obtained at the peak of the R-wave
in the ECG. Diameters were measured from intima to
intima using calipers with a 0.1 mm resolution. The mean
of three diameter measurements and flow measurements
were used in the calculation of FMD and flow responses.
Maximal dilation was in each case observed 1 min after
cuff release in each group, and those data are therefore
presented in the results. Shear rate was calculated as blood
flow velocity (cm/s) divided by diameter (cm), as de-
scribed by Pyke and Tschakovsky [25]. All ultrasound im-
ages were analysed in a random order, using EchoPAC
TM
(GE Vingmed Ultrasound) by an investigator who was
blinded to the group allocation of the subjects.
Blood profile
Blood samples were taken after 8 h of fasting. Citrated and
EDTA venous plasma samples were centrifuged at 1500 g
for 10 min at 4
◦
C, and stored at − 80
◦
Cforlateranalysis.
Serum ferritin, triacylglycerols, HDL (high-density
lipoprotein)-cholesterol, total cholesterol, haemoglobin,
high-sensitive CRP (C-reactive protein), Na
+
,K
+
,
creatinine, HbA
1c
(glycated haemoglobin), glucose and
insulin C-peptide were measured according to standard
procedures. Glucose and insulin C-peptide were re-
measured 2 h after an OGTT (oral glucose tolerance
test; 75 g of glucose in 3 dl of water within 5 min).
Total antioxidant status was measured in frozen serum
samples using the colorimetric total antioxidant status
assay (Randox Laboratories). The method is based upon
the incubation of ABTS [2,2
′
-azinobis-(3-ethylbenz-
othiazoline-6-sulfonic acid)] with metmyoglobin and
H
2
O
2
to produce the radical cation ABTS
+
.Thisradical
has a stable blue/green colour, which is measured at
600 nm. Antioxidants present in the sample weaken the
intensity of the colour in proportion to the concen-
tration. The assay was performed using an automated
C
⃝
The Authors Journal compilation
C
⃝
2008 Biochemical Society
286 I. E. Schjerve and others
system (Cobas Mira), according to the manufacturer’s
instructions. The concentration of oxidized LDL (low-
density lipoprotein) was measured in plasma using an
oxidized LDL ELISA kit (Mercodia), which is a solid-
phase enzyme immunoassay modified from the original
method [26]. All samples were analysed in duplicates.
˙
V
O
2max
˙
Vo
2max
was measured during uphill treadmill walking or
running (Woodway PPS 55 Med) using the Metamax II
system (Cortex), as described previously [9]. A warm-up
period for 10 min (50–60% of HR
max
) preceded the test.
A levelling off of
˙
Vo
2
, despite increased work load, and
RER (respiratory exchange ratio) ! 1.05 were used as
criteria for
˙
Vo
2max
.HRwasmeasuredduringthetest
(Polar type 610; Polar Electro), and HR
max
was defined
by adding 5 beats/min to the highest HR value obtained
during the
˙
Vo
2max
test.
Maximal leg strength
The maximal leg strength test was performed in a leg
press machine with the knee joints at 90
◦
. After a 10 min
warm-up by treadmill walking at 50–60 % of HR
max
and 10–15 warm-up repetitions in the leg press machine,
weights where added until 1RM was reached. The
number of repetitions necessary to reach 1RM varied
between three and ten. Subjects rested for at least 1 min,
but often for 2–3 min, before the next trial, depending
upon how hard they felt the previous repetition was.
Biochemistry of muscle biopsies
Muscle biopsies were obtained from musculus vastus
lateralis using a sterile 5-mm-diameter biopsy needle
(Bergstr
¨
om) [27] under local anaesthesia (2% lidocaine).
A 5–10 mm incision was made, the Bergstr
¨
om needle was
introduced into the muscle tissue, without using suction,
and three to four cuts were made. If present, superficial
blood was quickly removed, and the biopsy was frozen
in liquid nitrogen and stored at − 80
◦
Cforlateranalysis.
Muscle biopsies were homogenized in lysis buffer and
equal amounts of lysates were analysed by SDS/PAGE
and Western blot analysis with goat polyclonal
antibodies against PGC-1α (peroxisome-proliferator-
activated receptor γ co-activator 1α)(K-15;SantaCruz
Biotechnology). Gels were re-probed with a monoclonal
antibody against α-actin (Sigma) for normalization.
Protein levels were detected by chemiluminescence and
quantified by densitometry.
Skeletal muscle SERCA (sarcoplasmic/
endoplasmic reticulum Ca
2+
ATPase)
activity
Decreased maximal rate of Ca
2+
re-uptake into the
sarcoplasmic reticulum is inversely related to increased
skeletal muscle fatigue in individuals with low aerobic
capacity [9]. To measure this, Ca
2+
(50 µmol/l) was
added to skinned muscle fibres from the vastus lateralis
muscle to induce a rapid increase in [Ca
2+
], and the
kinetics of the subsequent decline in [Ca
2+
]were
analysed with Fura-2 on an epifluorescence microscope
(Diaphot-TMD; Nikon) to assess maximum SERCA-1
and -2 transport capacity, as described previously [28].
Body composition and BP
(blood pressure)
Dual-energy X-ray absorptiometry scanning (Hologic
Discovery-A; Integrity Medical Systems) was used to
measure body composition immediately after endothelial
function was measured, i.e. after 8–9 h of fasting, to
decrease large variations in hydration status. The waist/
hip ratio was measured at the midpoint between
the lower border of the ribs and the upper border of the
pelvis (waist), and at the trochanter major (hip) [3,29].
BP was measured by a trained physiologist with a
hand-held sphygmomanometer (Tycos) while the patient
was sitting and had rested for at least 5 min in a quiet
room. BP was measured at the same time of the day for
each individual at pre- and post-test. The first reading
was discarded and the mean of the next three consecutive
readings with a coefficient of variation < 15 % was used
in the present study, with additional readings if required.
Statistics
Before using parametric tests, the assumption of
normality was verified using the Shapiro–Wilk W
test. We used a two-way ANOVA to assess group–
time interactions (group×time; 2×2). The Bonferroni
post-hoc test adjusted for multiple comparisons was
used to identify the statistical differences between the
three groups. Pearson’s correlation coefficient was used
to determine potential relationships between FMD
and parameters changing in parallel; only significant
correlations are shown. Results are means
+
−
S.E.M., and
P < 0.05 indicates significant differences.
RESULTS
Baseline characteristics
The three groups did not differ significantly in any of the
parameters at baseline (Table 1).
˙
V
O
2max
Asignificantgroup–timeinteractionwasfoundfor
˙
Vo
2max
(F = 26.4, P < 0.001).
˙
Vo
2max
increased by 10, 16
and 33 % (all P < 0.01) in the strength training, moderate-
intensity and high-intensity groups respectively, and
thus high-intensity aerobic training had a greater effect
than strength training or moderate-intensity aerobic
training (Figure 1A). No difference in the increase in
˙
Vo
2max
occurred between the strength training and
C
⃝
The Authors Journal compilation
C
⃝
2008 Biochemical Society
Effect of training programmes on cardiovascular health in obese adults 287
Table 1
Baseline characteristics
Values are means
+
−
S.E.M. No significant differences were observed between the groups. lbm, lean body mass.
Group
Characteristic Strength training Moderate-intensity training High-intensity training
Age (years) 46.2
+
−
2.9 44.4
+
−
2.1 46.9
+
−
2.2
Height (cm) 169.1
+
−
2.6 167.7
+
−
2.9 175.9
+
−
2.2
Gender (
n
)(male/female) 2/11 3/10 3/11
Body weight (kg) 98.8
+
−
4.5 104.1
+
−
4.5 114.0
+
−
5.7
BMI (kg/m
2
)34.5
+
−
1.4 36.7
+
−
1.4 36.6
+
−
1.2
Body fat (%) 41.1
+
−
1.3 43.6
+
−
1.5 40.6
+
−
1.4
Lean body mass (kg) 63.1
+
−
5.7 66.3
+
−
6.8 67.1
+
−
3.8
Waist/hip ratio 0.90
+
−
0.03 0.90
+
−
0.03 1.00
+
−
0.03
HR
max
(beats/min) 173
+
−
7183
+
−
2170
+
−
5
˙
V
O
2max
(ml · lbm
−1
· min
−1
)38.3
+
−
4.1 37.8
+
−
4.8 39.7
+
−
6.8
˙
V
O
2max
(ml · kg
−1
of body weight · min
−1
)25.4
+
−
1.9 25.1
+
−
1.4 23.6
+
−
1.3
RER 1.12
+
−
0.04 1.14
+
−
0.02 1.14
+
−
0.03
1RM (kg) 174.1
+
−
13.0 162.8
+
−
19.1 180.6
+
−
13.4
Glucose (mmol/l) 5.4
+
−
0.3 6.2
+
−
1.1 5.2
+
−
0.1
Cholesterol (mmol/l) 6.3
+
−
0.3 5.8
+
−
0.3 6.3
+
−
0.2
Triacylglycerols (mmol/l) 2.0
+
−
0.3 1.5
+
−
0.3 1.2
+
−
0.1
HDL-cholesterol (mmol/l) 1.3
+
−
0.1 1.4
+
−
0.1 1.3
+
−
0.1
Haemoglobin (g/dl) 14.4
+
−
0.3 13.9
+
−
0.3 14.5
+
−
0.3
Figure 1
˙
V
O
2max
(A), peak O
2
pulse (B), 1RM (C), PGC-1α level (D) and SERCA activity (E) in subjects undergoing
high-intensity aerobic exercise, moderate-intensity aerobic exercise or strength training
Values are means
+
−
S.E.M. ns, not significant. lbm, lean body mass.
C
⃝
The Authors Journal compilation
C
⃝
2008 Biochemical Society
288 I. E. Schjerve and others
moderate-intensity groups (Figure 1). The RER was not
significantly different from that measured at pre-test
in any of the groups (Table 1). Post-test RERs were
1.10
+
−
0.02, 1.12
+
−
0.01, and 1.10
+
−
0.03 in the strength
training, moderate-intensity and high-intensity groups
respectively. All subjects satisfied the criteria for
˙
Vo
2max
,
i.e. a levelling-off despite increased work load and a
RER > 1.05, as well as being < 5 beats from actual
HR
max
.HR
max
was reached both at pre-test (Table 1) and
post-test (172
+
−
4,181
+
−
4 and 171
+
−
3beats/minforthe
strength training, moderate-intensity and high-intensity
groups respectively).
Asignificantgroup–timeinteractionwasfoundfor
the O
2
pulse (F = 22.3, P < 0.001). Peak O
2
pulse (in
ml/HR
max
) improved in all groups (P < 0.01), indicating
that the maximal stroke volume increased [30]. No
difference was observed in the increase in the O
2
pulse
between the strength training and moderate-intensity
groups, but the high-intensity group had a greater
improvement in peak O
2
pulse compared with the other
two groups (Figure 1B).
Maximal strength
A significant time–group interaction was observed for
maximal strength (F = 8.1, P < 0.01). The strength train-
ing group improved 1RM by 25 % (P < 0.001), whereas
there were no changes in the moderate-intensity or
high-intensity groups (Figure 1C).
Skeletal muscle PGC-1α and SERC A
PGC-1α is a master regulator of mitochondrial bio-
genesis and enzymes of fatty acid metabolism [31,32].
A time–group interaction was observed for the level of
PGC-1α (F = 6.1, P < 0.01).
Both strength training and high-intensity aerobic
training increased PGC-1α protein levels (P < 0.01), but
moderate-intensity aerobic training did not (Figure 1D).
The maximal rate of Ca
2+
re-uptake into the sarcoplasmic
reticulum by SERCA in skeletal muscles increased by
73 and 72 % after high-intensity aerobic training and
strength training respectively, but moderate-intensity
aerobic training had no effect (Figure 1E).
Endothelial function
A significant time–group interaction was found for
FMD (F = 5.9, P < 0.01). FMD improved significantly
(P < 0.001) in all of the groups (Figures 2A, 2C and 2E).
High-intensity aerobic training had a significantly greater
effect on endothelial function compared with strength
training and moderate-intensity groups (P < 0.05),
although there was no statistical difference between the
latter two groups (Figures 2A, 2C and 2E). The resting
diameter of the brachial artery was similar in all three
groups and did not change during the experimental period
(Table 2). Additionally, peak blood flow did not change
(Figures 2B, 2D and 2F), so that shear rates were similar
between the three groups and were not influenced by
the training regimens (Table 2). Therefore the observed
changes in F MD were not due to a change in artery
diameter or shear rate, as the same group differences were
seen after normalizing FMD for potential differences in
shear rate (Figures 2B, 2D and 2F). Exercise training had
no impact on endothelium-independent dilation induced
by NTG (Table 2, and Figures 2A, 2C and 2E).
Blood markers
Agroup–timeinteractionwasobservedforoxidizedLDL
(F = 4.2, P < 0.05). Oxidized LDL decreased significantly
after strength training (P < 0.005) and moderate-intensity
aerobic training (P < 0.04), but not after high-inten-
sity aerobic training (Figure 3A). Only strength training
increased total antioxidant status (P < 0.03; Figure 3B),
but no group–time interaction was observed. None of
the traditional blood markers were affected by any of the
training programmes, as serum ferritin, triacylglycerols,
HDL-cholesterol, total cholesterol, haemoglobin, high-
sensitive CRP, Na
+
,K
+
, creatinine, HbA
1c
, glucose
and insulin C-peptide remained unchanged in all of the
groups.
Body composition
Asmall,butsignificant,group–timeinteractionforbody
weight (F = 4.4, P < 0.05) was observed. Body weight
decreased by 3 % (P < 0.005) and 2 % (P < 0.04) after
moderate-intensity and high-intensity aerobic training
respectively, whereas no change was observed in the
strength training group (Figure 4A). A decrease in BMI
was observed in both the moderate-intensity (from
36.7
+
−
1.4 to 35.6
+
−
1.4 kg/m
2
; P < 0.007) and high-
intensity (from 36.6
+
−
1.2 to 36.0
+
−
1.2 kg/m
2
; P < 0.04)
groups, whereas strength training had no effect on BMI.
Body fat decreased 2.5 % (P < 0.03) and 2.2% (P < 0.02)
in the moderate-intensity and high-intensity groups
respectively, but not in the strength training group
(Figure 4B). There were no changes in the waist/hip ratio
in any of the groups (results not shown).
BP
No changes were observed for SBP (systolic BP) (results
not shown). In contrast, DBP (diastolic BP) decreased by
9% (P < 0.02) in the moderate-intensity group and
by 7 % (P < 0.002) in the high-intensity group, whereas
no change was observed in the strength training group
(Figure 4C). The group–time interaction was significant
for DBP (F = 2.0, P < 0.05).
Correlations
We observed a low, but significant, correlation between
FMD and DBP (R = − 0.4, P = 0.044), and a correlation
between FMD and
˙
Vo
2max
(R = 0.54, P < 0.001).
C
⃝
The Authors Journal compilation
C
⃝
2008 Biochemical Society
Effect of training programmes on cardiovascular health in obese adults 289
Figure 2
Endothelial function in subjects undergoing high-intensity aerobic training, moderate-intensity aerobic training
or strength training
Results are means
+
−
S.E.M. (A, C and E) FMD, as a measure of endothelial function, presented as the percentage increase from baseline diameter of the vessel. (B, D
and F) FMD normalized for shear rate.
∗
Significantly greater improvement (
P
< 0.05) than after strength training or moderate-intensity aerobic exercise. NTG-FMD,
NTG-induced FMD; n.s., not significant.
Table 2
Baseline, peak diameter and shear rate in the brachial artery
Values are means
+
−
S.E.M. Shear rate is calculated as flow (cm/s) divided by artery diameter (cm).
Group
Strength training Moderate-intensity training High-intensity training
Measurement Pre- Post- Pre- Post- Pre- Post-
Baseline diameter (cm) 0.420
+
−
0.03 0.410
+
−
0.04 0.400
+
−
0.05 0.401
+
−
0.04 0.402
+
−
0.04 0.391
+
−
0.03
Peak diameter (cm) 0.432
+
−
0.04 0.436
+
−
0.03 0.412
+
−
0.03 0.430
+
−
0.02 0.411
+
−
0.03 0.429
+
−
0.02
Peak NTG diameter (cm) 0.481
+
−
0.06 0.470
+
−
0.05 0.461
+
−
0.06 0.472
+
−
0.07 0.461
+
−
0.04 0.462
+
−
0.05
Shear rate (flow/diameter) 441
+
−
37 438
+
−
40 446
+
−
29 442
+
−
36 438
+
−
39 437
+
−
38
DISCUSSION
The major findings of the present study are that (i)
high-intensity aerobic interval training was better at
improving endothelial function than either continuous
moderate-intensity aerobic training or strength training,
and (ii) strength training and moderate-intensity aerobic
training were equally efficient in improving endothelial
function in obese adults, albeit less efficiently than high-
intensity aerobic interval training. Thi s demonstrates that
C
⃝
The Authors Journal compilation
C
⃝
2008 Biochemical Society
290 I. E. Schjerve and others
Figure 3
Oxidized LDL (A) and total antioxidant status
(B) in subjects undergoing high-intensity aerobic exercise,
moderate-intensity aerobic exercise or strength training
Values are means
+
−
S.E.M.
P
values indicate a significant difference between pre-
and post-exercise. ns, not significant.
it is possible to reverse impaired endothelial function in
subjects that are hindered from performing whole-body
endurance training.
FMD (endothelial function)
Shear stress to the arterial wall stimulates endothelial
production of NO which subsequently induces vessel
dilation. The dependence of exercise intensity suggests
that high-intensity aerobic training induces a greater shear
stress during exercise compared with moderate-intensity
aerobic training, consistent with previous results [9]. Res-
ults from the present study suggest that strength training
appears to induce a shear stress similar to that associated
with moderate-intensity aerobic training. It cannot be
ruled out that the improvement in endothelial function
in the strength training group is caused by the 15 min
warm-up periods; however, if this was the case, it would
mean that 15 min of walking at 40–50% of HR
max
would equal 47 min at 60–70 % of HR
max
but, because of
the dose–response relationship between moderate- and
high-intensity aerobic training reported in the present
study and elsewhere [8,9,14,16] in improving endothelial
function, this assumption is unlikely, although it
should be tested in future studies. In fact, it h as
been demonstrated that 1 year of strength training
improves endothelial function in overweight women,
independently of changes in major cardiovascular risk
factors such as BMI, body composition, BP, fasting blood
lipids, and fasting blood glucose and insulin [33]. In
contrast, 12 weeks of whole-body resistance training in
healthy young men did not change endothelial function
(FMD) or shear rate, but increased arterial diameter and,
hence, blood flow [34]. Thus it seems likely that strength
training may improve endothelial function in overweight
and obese subjects, but not in healthy subjects. The
underlying mechanisms for why strength training should
affect endothelial function in these populations remain
largely unknown, although improved antioxidant status
after strength training may indicate that oxidative stress
by ROS (reactive oxygen species) and oxidized LDL
is decreased, which would enhance the bioavailability
of NO. However, these findings should be interpreted
cautiously as, for unknown reasons, the baseline values
for total antioxidant status in the strength training group
were twice that in the other two groups at baseline (and
at post-test), and this may well be the reason that only
strength training improved antioxidant status. Further
studies are needed to determine whether improved
FMD due to strength training involves actual changes
in antioxidant status. Antioxidative effects of aerobic
exercise training have been reported previously in patients
Figure 4
Body weight (A), body fat (B), expressed as a percentage of total body weight, and DBP (C) in subjects undergoing
high-intensity aerobic exercise, moderate-intensity aerobic exercise or strength training
Values are means
+
−
S.E.M.
P
values indicate a significant difference between pre- and post-exercise. ns, not significant.
C
⃝
The Authors Journal compilation
C
⃝
2008 Biochemical Society
Effect of training programmes on cardiovascular health in obese adults 291
with heart failure [9,35]; however, why no effects of high-
intensity or moderate-intensity aerobic training were
found in the present study is unknown, but may be linked
to the different study populations.
Body composition and BP
High BP is associated with increased risk of stroke
and ischaemic heart disease [36]. We found that both
high-intensity and moderate-intensity aerobic training,
but not strength training, significantly decreased DBP
by 6–8 mmHg. On the basis of a meta-analysis of
1millionadults,thiswouldtranslatetoa30%lower
risk of premature deaths [36]. The observed correlation
between FMD and DBP are consistent with other studies
[37,38] and indicate that improved endothelial function
after the endurance training regimens contributes to the
decreased DBP. On the other hand, endothelial function
was also improved after strength training, which was
not linked to a decrease in DBP. This suggests that other
factors may be more important in the regulation of BP
than changes in FMD and should be studied further.
In the present study, both of the aerobic training
regimens caused small, but significant, decreases in body
weight. Although both obesity and aerobic capacity are
strong and independent prognostic markers of cardio-
vascular mortality, the link between aerobic capacity and
mortality appears to be stronger [39], and it has therefore
been suggested that improving aerobic capacity is more
important than losing weight [40].
Oxygen uptake
As expected, the greatest improvement in
˙
Vo
2max
was
observed after high-intensity aerobic interval training,
but, surprisingly, strength training increased
˙
Vo
2max
to
asmaller,butnotstatisticallydifferent,extentcompared
with moderate-intensity aerobic training. High intensity
yielding a higher effect than moderate intensity during
an aerobic training programme confirms previous studies
in both healthy subjects [16] and patients with post-
infarction heart failure [9]. Previous studies involving
patients with coronary artery disease employing aerobic
interval exercise with elements of high intensity, as in the
present study, have also indicated that the development
of
˙
Vo
2max
depends on exercise intensity [8,41]. Although
the various studies are not directly comparable due to
different exercise protocols, they demonstrate however
that high-intensity aerobic exercise is associated with
the greatest improvements in
˙
Vo
2max
. The present study
also suggests that the stroke volume of the heart is a
mediator of
˙
Vo
2max
, as indicated by a greater O
2
pulse
after high-intensity aerobic interval training compared
with the other two groups.
The reason as to why strength training increases
˙
Vo
2max
is not fully understood, but it may be that a greater
1RM allows for more ordinary daily activities, such
as walking, and thereby permits an increase in general
activity levels. This was, however, not controlled for in
the present study. In addition, the possibility remains
that the improvement in
˙
Vo
2max
after strength training
was caused by the 15 min low-intensity warm-up period,
although this would be unlikely, as discussed above.
Skeletal muscle
In line with our recent studies in patients with heart fail-
ure [9] or the metabolic syndrome [42], PGC-1α, a master
regulator of energy metabolism [31,32,41], increased after
high-intensity aerobic training, but not after moderate-
intensity aerobic training. The observation that strength
training also increased PGC-1α levels is, however, novel.
The reason for the differences in training response is
unknown, but it is conceivable that the ischaemic con-
ditions in skeletal muscle during high-intensity aerobic
interval training and strength training are a considerable
stimulus for the up-regulation of muscle mechanisms
that improve aerobic metabolism. Our hypothesis was
supported by the findings that exercise with restricted,
rather than non-restricted, blood flow induced a greater
increase in PGC-1α mRNA levels [43]. High-intensity
interval and maximal strength training would also restrict
blood flow and/or induce local hypoxia in the skeletal
muscles. This may well be the mechanism for strength
training improving
˙
Vo
2max
in the present study and
resting metabolism in other studies [44].
Interestingly, decreased maximal rate of Ca
2+
re-
uptake into the sarcoplasmic reticulum increased only
after strength training and high-intensity aerobic interval
training. As those were the only training programmes
that also increased PGC-1α levels, it may suggest that
increased metabolic and ATP-producing capacity [32]
allows for a concomitant increase in the capacity of the
SERCA to transport Ca
2+
, as it is an ATPase (‘ATP us er’).
Although not investigated in the present study, this may
suggest that high-intensity aerobic interval and strength
training programmes improve overall contractile
performance in the skeletal muscle.
Conclusions
The present study demonstrates that both aerobic
exercise training at either high or moderate intensities
and high-intensity strength training improve endothelial
function and decrease the cardiovascular risk profile in
obese adults. However, high-intensity aerobic interval
training results in a greater improvement in endothelial
function and a decrease in the cardiovascular risk profile
in these subjects than moderate-intensity aerobic training
or strength training. Maximal strength training improved
endothelial function and
˙
Vo
2max
equally as efficiently as
moderate-intensity aerobic training. Improved endothe-
lial function after maximal strength training occurred
in conjunction with improved antioxidant status and
decreased levels of oxidized LDL, indicating a possible
mechanistic explanation. Moreover, enhanced
˙
Vo
2max
C
⃝
The Authors Journal compilation
C
⃝
2008 Biochemical Society
292 I. E. Schjerve and others
after strength training and high-intensity aerobic interval
training was associated with higher expression of PGC-
1α and improved SERCA activity in the skeletal muscle.
These observations demonstrate that it might be possible
to reverse impaired endothelial function, decrease cardio-
vascular risk and improve exercise capacity in subjects
that have difficulty performing whole-body aerobic
training.
ACKNOWLEDGMENTS
The present study was supported by grants from
the Norwegian Council of Cardiovascular Disease, the
Norwegian Research Council (Funding for Outstanding
Young Investigators to U.W.), Funds for Cardiovascular
and Medical Research at St. Olav’s University Hospital,
Trondheim, and the Torstein Erbo’s Foundation, Tron-
dheim. The funding organizations had no role in the
design and conduct of the study, in the collection,
analysis, and interpretation of the data, or in the
preparation, review or approval of the manuscript.
REFERENCES
1 James, P. T., Rigby, N. and Leach, R. International Obesity
Task Force (2004) The obesity epidemic, metabolic
syndrome and future prevention strategies. Eur. J.
Cardiovasc. Prev. Rehabil. 11,3–8
2 NHLBI Obesity Task Force (1998) Clinical guidelines on
the identification, evaluation, and treatment of overweight
and obesity in adults-the evidence report. Obes. Res. 6,
51S–209S
3 Kopelman, P. G. (2000) Obesity as a medical problem.
Nature 404,635–643
4 Watts, K., Beye, P., Siafarikas, A. et al. (2004) Exercise
training normalizes vascular dysfunction and improves
central adiposity in obese adolescents. J. Am.
Coll. Cardiol. 43,1823–1827
5 Deanfield, J. E., Halcox, J. P. and Rabelink, T. J. (2007)
Endothelial function and dysfunction: testing and clinical
relevance. Circulation 115,1285–1295
6 Kavanagh, T., Mertens, D. J., Hamm, L. F. et al. (2002)
Prediction of long-term prognosis in 12 169 men referred
for cardiac rehabilitation. Circulation 106,666–671
7 Myers, J., Prakash, M., Froelicher, V., Do, D., Partington,
S. and Atwood, J. E. (2002) Exercise capacity and mortality
among men referred for exercise testing. N. Engl. J. Med.
346,793–801
8 Rognmo, O., Hetland, E., Helgerud, J., Hoff, J. and
Slordahl, S. A. (2004) High intensity aerobic interval
exercise is superior to moderate intensity exercise for
increasing aerobic capacity in patients with coronary artery
disease. Eur. J. Cardiovasc. Prev. Rehabil. 11,216–222
9 Wisløff, U., Stoylen, A., Loennechen, J. P. et al. (2007)
Superior cardiovascular effect of aerobic interval training
versus moderate continuous training in heart failure
patients: a randomized study. Circulation 115,3086–3094
10 Meyer, A. A., Kundt, G., Lenschow, U., Schuff-Werner, P.
and Kienast, W. (2006) Improvement of early vascular
changes and cardiovascular risk factors in obese children
after a six-month exercise program. J. Am. Coll. Cardiol.
48,1865–1870
11 Haskell, W. L., Lee, I. M., Pate, R. R. et al. (2007) Physical
activity and public health: updated recommendation for
adults from the American College of Sports Medicine and
the American Heart Association. Med. Sci. Sports Exercise
39,1423–1434
12 Dubach, P., Myers, J., Dziekan, G. et al. (1997) Effect of
exercise training on myocardial remodeling in patients with
reduced left ventricular function after myocardial
infarction: application of magnetic resonance imaging.
Circulation 95,2060–2067
13 Hambrecht, R., Gielen, S., Linke, A. et al. (2000) Effects of
exercise training on left ventricular function and peripheral
resistance in patients with chronic heart failure:
arandomizedtrial.JAMA,J.Am.Med.Assoc.283,
3095–3101
14 Lee, I. M., Sesso, H. D., Oguma, Y. and Paffenbarger, Jr,
R. S. (2003) Relative intensity of physical activity and risk
of coronary heart disease. Circulation 107,1110–1116
15 Fletcher, G. F., Balady, G. J., Amsterdam, E. A. et al. (2001)
Exercise standards for testing and training: a statement for
healthcare professionals from the American Heart
Association. Circulation 104,1694–1740
16 Helgerud, J., Hoydal, K., Wang, E. et al. (2007) Aerobic
high-intensity intervals improve
˙
Vo
2max
more than
moderate training. Med. Sci. Sports Exercise 39,665–671
17 Gaesser, G. A. and Rich, R. G. (1984) Effects of high- and
low-intensity exercise training on aerobic capacity and
blood lipids. Med. Sci. Sports Exercise 16,269–274
18 Bahr, R. and Sejersted, O. M. (1991) Effect of intensity of
exercise on excess postexercise O
2
consumption.
Metab. Clin. Exp. 40,836–841
19 Gilette, C. A., Bullough, R. C. and Melby, C. L. (1994)
Postexercise energy expenditure in response to acute
aerobic or resistance exercise. Int. J. Sport Nutr. 4,
347–360
20 Hoff, J. and Helgerud, J. (2004) Endurance and strength
training for soccer players: physiological considerations.
Sports Med. 34,165–180
21 Behm, D. G. and Sale, D. G. (1993) Velocity specificity of
resistance training. Sports Med. 15,374–388
22 Folland, J. P. and Williams, A. G. (2007) The adaptations to
strength training: morphological and neurological
contributions to increased strength. Sports Med. 37,
145–168
23 Corretti, M. C., Anderson, T. J., Benjamin, E. J. et al.
(2002) Guidelines for the ultrasound assessment of
endothelial-dependent flow-mediated vasodilation of the
brachial artery: a report of the International Brachial
Artery Reactivity Task Force. J. Am. Coll. Cardiol. 39,
257–265
24 Raitakari, O. T. and Celermajer, D. S. (2000)
Flow-mediated dilatation. Br. J. Clin. Pharmacol. 50,
397–404
25 Pyke, K. E. and Tschakovsky, M. E. (2005) The
relationship between shear stress and flow-mediated
dilatation: implications for the assessment of endothelial
function. J. Physiol. 568,357–359.
26 Holvoet, P., Donck, J., Landeloos, M. et al. (1996)
Correlation between oxidized low density lipoproteins and
von Willebrand factor in chronic renal failure.
Thromb. Haemostasis 76,663–669
27 Bergstrom, J. (1975) Percutaneous needle biopsy of skeletal
muscle in physiological and clinical research. Scand. J. Clin.
Lab. Invest. 35,609–616
28 Kemi, O. J., Ceci, M., Condorelli, G., Smith, G. L. and
Wisløff, U. (2008) Myocardial sarcoplasmic reticulum
Ca
2+
ATPase function is increased by aerobic
interval training. Eur. J. Cardiovasc. Prev. Rehabil. 15,
145–148
29 Lakka, H. M., Laaksonen, D. E., Lakka, T. A. et al. (2002)
The metabolic syndrome and total and cardiovascular
disease mortality in middle-aged men. JAMA, J. Am.
Med. Assoc. 288,2709–2716
30 Wasserman, K., Hansen, J. E., Sue, D. Y., Casaburi, R. and
Whipp, B. J. (1999) Principles of Exercise Testing and
Interpretation, 3rd edition, p. 77, Lippincott, Williams &
Wilkins, Baltimore
31 Garnier, A., Fortin, D., Zoll, J. et al. (2005) Coordinated
changes in mitochondrial function and biogenesis in
healthy and diseased human skeletal muscle. FASEB J. 19,
43–52
C
⃝
The Authors Journal compilation
C
⃝
2008 Biochemical Society
Effect of training programmes on cardiovascular health in obese adults 293
32 Ventura-Clapier, R., Garnier, A. and Veksler, V. (2004)
Energy metabolism in heart failure. J. Physiol. 555,1–13
33 Olson, T. P., Dengel, D. R., Leon, A. S. and Schmitz, K. H.
(2006) Moderate resistance training and vascular health in
overweight women. Med. Sci. Sports Exercise 38,
1558–1564
34 Rakobowchuk, M., McGowan, C. L., de Groot, P. C.,
Hartman, J. W., Phillips, S. M. and MacDonald, M. J.
(2005) Endothelial function of young healthy males
following whole body resistance training. J. Appl. Physiol.
98,2185–2190
35 Linke, A., Adams, V., Schulze, P. C. et al. (2005)
Antioxidative effects of exercise training in patients with
chronic heart failure: increase in radical scavenger enzyme
activity in skeletal muscle. Circulation 111,
1763–1770
36 Lewington, S., Clarke, R., Qizilbash, N., Peto, R. and
Collins, R. (2002) Age-specific relevance of usual blood
pressure to vascular mortality: a meta-analysis of
individual data for one million adults in 61 prospective
studies. Lancet 360,1903–1913
37 Thomas, G. N., Chook, P., Qiao, M., Huang, X. S., Leong,
H. C., Celermajer, D. S. and Woo, K. S. (2004) Deleterious
impact of ‘high normal’ glucose levels and other metabolic
syndrome components on arterial endothelial function and
intima-media thickness in apparently healthy Chinese
subjects: the CATHAY study. Arterioscler. Thromb.
Vasc. Biol. 24,739–743
38 Yufu, K., Takahashi, N., Hara, M., Saikawa, T. and
Yoshimatsu, H. (2007) Measurement of the brachial-ankle
pulse wave velocity and flow-mediated dilatation in young,
healthy smokers. Hypertens. Res. 30,607–612
39 Blair, S. N. and Brodney, S. (1999) Effects of physical
inactivity and obesity on morbidity and mortality: current
evidence and research issues. Med. Sci. Sports Exercise 31,
S646–S662
40 Gaesser, G. A. (1999) Thinness and weight loss: beneficial
or detrimental to longevity? Med. Sci. Sports Exercise 31,
1118–1128
41 Finck, B. N. and Kelly, D. P. (2007) Peroxisome
proliferator-activated receptor γ coactivator-1 (PGC-1)
regulatory cascade in cardiac physiology and disease.
Circulation 115,2540–2548
42 Tjønna, A. E., Lee, S. J., Rognmo, Ø. et al. (2008) Aerobic
interval training versus continuous moderate exercise as a
treatment for the metabolic syndrome: a pilot study,
Circulation, doi: 10.1161/CIRCULATIONAHA.
108.772822
43 Norrbom, J., Sundberg, C. J., Ameln, H., Kraus, W. E.,
Jansson, E. and Gustafsson, T. (2004) PGC-1α mRNA
expression is influenced by metabolic perturbation in
exercising human skeletal muscle. J. Appl. Physiol. 96,
189–194
44 Dolezal, B. A. and Potteiger, J. A. (1998) Concurrent
resistance and endurance training influence basal metabolic
rate in nondieting individuals. J. Appl. Physiol. 85,695–700
Received 20 September 2007/26 February 2008; accepted 13 March 2008
Published as Immediate Publication 13 March 2008, doi:10.1042/CS20070332
C
⃝
The Authors Journal compilation
C
⃝
2008 Biochemical Society
