Maeng-Kyu Kim, Tsugio Tomita, Mi-Ji Kim, Hiroyuki Sasai, Seiji Maeda and

Kiyoji Tanaka
J Appl Physiol 106:5-11, 2009. First published Oct 16, 2008; doi:10.1152/japplphysiol.90756.2008

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Aerobic exercise training reduces epicardial fat in obese men
Maeng-Kyu Kim,1 Tsugio Tomita,2 Mi-Ji Kim,1 Hiroyuki Sasai,1 Seiji Maeda,1 and Kiyoji Tanaka1
1
Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba; and 2Department of Radiation,
Higashi Toride Hospital, Ibaraki, Japan
Submitted 16 June 2008; accepted in final form 2 October 2008
Kim MK, Tomita T, Kim MJ, Sasai H, Maeda S, Tanaka K.
Aerobic exercise training reduces epicardial fat in obese men. J Appl
Physiol 106: 5–11, 2009. First published October 16, 2008;
doi:10.1152/japplphysiol.90756.2008.—The purpose of this study
was to determine the effects of exercise training on ventricular
epicardial fat thickness in obese men and to investigate the relation-
ship of the change in epicardial fat thickness to changes in abdominal
fat tissue following exercise training. Twenty-four obese middle-aged
men [age, 49.4 ⫾ 9.6 yr; weight, 87.7 ⫾ 11.2 kg; body mass index
(BMI), 30.7 ⫾ 3.3 kg/m2; peak oxygen consumption, 28.4 ⫾ 7.2
ml 䡠 kg⫺1 䡠 min⫺1; means ⫾ SD] participated in this study. Each par-
ticipant completed a 12-wk supervised exercise training program
(60 –70% of the maximal heart rate; 60 min/day, 3 days/wk) and
underwent a transthoracic echocardiography. The epicardial fat thick-
ness on the free wall of the right ventricle was measured from both
parasternal long- and short-axis views. The visceral adipose tissue
(VAT) and subcutaneous adipose tissues were measured by computed
tomography. Following exercise training, the epicardial fat thickness
was significantly decreased (P ⬍ 0.001). The percentage change of
epicardial fat thickness was twice as high compared with those of
waist, BMI, and body weight of original values (P ⬍0.05). There was
a significant relationship (r ⫽ 0.525, P ⫽ 0.008) between changes in
the epicardial fat thickness and VAT with exercise training. Stepwise
multiple regression analysis revealed that the change in VAT, change
in systolic blood pressure, and change in quantitative insulin sensi-
tivity check index were independently related to the change epicardial
fat thickness (P ⬍ 0.05). The ventricular epicardial fat thickness is
reduced significantly after aerobic exercise training and is associated
with a decrease in VAT. These results suggest that aerobic exercise
training may be an effective nonpharmacological strategy for decreas-
ing the ventricular epicardial fat thickness and visceral fat area in
obese middle-aged men.
abdominal adiposity; systolic blood pressure; insulin resistance
THE INCIDENCE AND PREVALENCE of obesity are significantly
increasing all over the world, and obesity represents a major
health hazard because of the independent risks that are directly
related to increased body mass index per se, in addition to the
associated potential risks for the development of diabetes,
dyslipidemia, and hypertension (32). Emerging evidence has
shown that in obesity, excessive fat accumulation is ubiquitous
in the liver (45), abdominal viscera, and subcutaneous tissues
(37) and within myocytes (43), all of which lead to worsening
of insulin sensitivity in the general population and impaired
metabolic control in diabetic patients (47). Besides the above
sites of adipose accumulation, epicardial adipose tissue has
been potentially recognized as a marker of cardiac risk and of
the development of an unfavorable metabolic risk profile (16,
18). Echocardiographically measured epicardial fat on the free
Address for reprint requests and other correspondence: K. Tanaka, Dept. of
Sports Medicine for Health and Disease, Univ. of Tsukuba, Tsukuba, Ibaraki
305-8577, Japan (e-mail: tanaka@taiiku.tsukuba.ac.jp).
http://www. jap.org 8750-7587/09 $8.00 Copyright © 2009 the American Physiological Society
J Appl Physiol 106: 5–11, 2009.
First published October 16, 2008; doi:10.1152/japplphysiol.90756.2008.
wall of the right ventricle has been shown to be true visceral fat
with all the characteristics of highly insulin-resistant tissues
(18) and is related to an increase in the left ventricular mass
(19). Therefore, effective treatments are needed to decrease the
amount of epicardial fat in the obese. Considering this factor,
a recent study used a recently validated echocardiographic
measure and reported that weight loss after bariatric surgery in
severely obese patients contributed to a decrease in the epicar-
dial adipose tissue (49). More recently, the very low calorie
diet of a weight loss program decreased epicardial fat thick-
ness, which is associated with changes in fat distribution in
Downloaded from jap.physiology.org on August 7, 2010
severely obese subjects (20).
Exercise is well known as the cornerstone treatment for
obesity-related metabolic complications, including insulin re-
sistance, hypertension, impaired glucose tolerance or diabetes,
hyperinsulinemia, and dyslipidemia, that are characterized by
elevated adipose accumulation (14, 46). Physical activity is
known as a common prescription to reduce abdominal adipose
deposition and obesity (37–38) and to improve glucose toler-
ance and lipid metabolism through its acute and chronic ef-
fects, and physical activity has been associated with a reduc-
tion in abdominal and visceral fat (31, 40); surprisingly, how-
ever, to the best of our knowledge, only a few human studies
have been conducted to determine whether exercise training
changes the epicardial fat thickness.
The purpose of the present study was, therefore, to deter-
mine whether aerobic exercise training without diet restriction
changes the ventricular epicardial fat thickness and whether the
changes in the abdominal visceral fat deposits are associated
with the epicardial fat thickness during exercise training in
middle-aged obese men.
MATERIALS AND METHODS
Participants. The subjects were recruited through advertisements in
local newspapers. In general, the volunteers were healthy, were not
consuming any medication known to alter glucose and lipid metabo-
lism, and were reportedly free of any diagnosed cardiovascular dis-
ease, any contraindication to exercise, or any known metabolic dis-
order. The nature, purpose, and potential risks of the study were
explained to all the subjects, and voluntary informed written consent
was obtained from all subjects before participation in the study. This
study was conducted in accordance with the guidelines proposed in
The Declaration of Helsinki and was approved by the Higashi Toride
Hospital, and the study protocol was reviewed and approved by the
Ethics Committee, University of Tsukuba, Japan. The metabolic
syndrome was defined according to the criteria of the Japan Society
for the Study of Obesity (8) based on the presence of 100 cm2 of
visceral fat area corresponding to waist circumference of 85 cm, plus
two or more comorbidities consisting of 1) fasting glucose level ⱖ
The costs of publication of this article were defrayed in part by the payment
of page charges. The article must therefore be hereby marked “advertisement”
in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
5
6 EPICARDIAL FAT AND EXERCISE TRAINING
110 mg/dl, 2) systolic blood pressure (SBP) ⱖ 130 mmHg and/or
diastolic blood pressure ⱖ 85 mmHg, and 3) triglyceride (TG) level ⱖ
150 mg/dl and/or high-density lipoprotein (HDL) level ⬍ 40 mg/dl.
Anthropometric measurements. Body height was measured to the
nearest 0.1 cm using a wall-mounted stadiometer (TBF-215; Tanita,
Tokyo, Japan), and body weight was measured to the nearest 0.01 kg
using calibrated electronic digital scales (TBF-215; Tanita) in bare-
foot subjects. Body mass index was calculated by dividing the weight
(in kg) by the square of the height (in m2). Waist circumference was
measured at the level of the umbilicus in lightly clothed participants
in the standing position. The mean of two consecutive records was
used as the measured value. Dual-energy X-ray absorptiometry
(DXA) was performed using a Lunar (software version 1.3Z, DPX-L;
Lunar, Madison, WI) to evaluate body composition, which was
assumed to consist of fat mass and fat- and bone-free mass, as
previously described (34). The pixels of soft tissue were used to
calculate the ratio of mass attenuation coefficients at 40 –50 keV (low
energy) and 80 –100 keV (high energy). The subjects were made to lie
supine with arms and legs at their sides during the 15-min scan;
radiation exposure was ⬍7 ␮Sv. All the scans were performed by the
same operator, and daily quality assurance tests were performed
according to the manufacturer’s directions. It places low demands on
the subjects’ performance, and it is, therefore, the most convenient in
the obese as well as elderly individuals. In the second measurement
session, abdominal visceral fat and subcutaneous fat area were mea-
sured using computed tomography (CT) scans (SOMATOM AR.C;
Siemens, Germany) set at 110 kVp and 50 mA. A single 5-mm scan
with a scanning time of 5 s was obtained, centered at the level of the
umbilicus (4th and 5th lumbar vertebrae) in the supine position with
the participants’ arms extended above the head during the measure-
ments. The images were digitized by optical density to separate the
bone, muscle, and fat compartments. The visceral fat and subcutane-
ous fat area were calculated using a computer software program (Fat
Scan; N2 system, Osaka, Japan), as described previously (30, 34). The
measurement sessions were separated by approximately 1–2 day,
depending on the participant’s schedule and the availability of CT.
Clinical assessment of epicardial adipose tissue. For direct assess-
ment of the epicardial adipose tissue, each participant underwent
echocardiography as proposed by Iacobellis et al. (15, 18). With the
subjects in the left lateral decubitus position, two-dimensionally
guided M-mode echocardiography was performed using an Envisor C
(Philips) with a 2.5-MHz transducer. The largest dimension of this
space was in the end-diastolic period and was measured from the
trailing edge to the leading edge on the free wall of the right ventricle;
this measurement was considered as the maximum epicardial fat
thickness in two standard echocardiographic views, namely the paraster-
nal long-axis and short-axis views, and an average of the measurements
on both views was obtained for offline analysis of the recorded videotape.
To decrease the variability, three cardiac cycles were read and measured
in the end-diastolic period of the right ventricle. At the analysis (before
and after the exercise training program), research personnel were
blinded to the baseline test results to minimize observation bias
according to a previously described study; this was necessary because
epicardial fat thickness was being carefully considered in relation to
the degree of weight loss (20, 49).
Anaerobic threshold and maximal aerobic capacity. The subjects
underwent a maximal graded exercise test on a cycling ergometer
(818E; Monark, Stockholm, Sweden) for evaluation of cardiovascular
function and simultaneous determination of the individual’s peak
oxygen uptake (V̇O2) and anaerobic threshold (AT). Following a
2-min warm-up at 0 W, the exercise was started at a workload of 15
W that was increased every 1 min by another 15 W until volitional
exhaustion. During the test, ventilation and expired gases were mea-
sured using an automated gas exchange measuring system (Oxycon ␣
system; Mijnhardt, Breda, The Netherlands), and the heart rate was
constantly observed at rest and during the exercise and recovery
periods using an ECG monitor (Dyna Scope; Fukudadenshi, Tokyo,
J Appl Physiol • VOL 106 • JANUARY 2009 •
Japan). AT, a discriminatory marker between cardiovascular and
pulmonary limitations to exercise (48), was determined from Vslope-
AT, which was plotted using the v-slope technique as described in an
earlier study (4). The carbon dioxide output (V̇CO2) vs. V̇O2 curve was
divided into two regions, each of which was fitted by linear regres-
sion, and the intersection between the two regression lines was
regarded as the Vslope-AT. The software of the Oxycon equipment
automatically established the regression lines and their crossing
points. The highest oxygen uptake achieved over 30 s was determined
as peak V̇O2 (V̇O2peak). The V̇O2peak was referred to the criteria
described by Tanaka et al. (44). Exercise testing was discontinued in
case of the following reasons: perceived exertion rating ⬎ 18;
achievement of ⬎90% of the age-predicted maximal heart rate or
extreme fatigue such that pedaling on the bicycle was not possible;
typical chest discomfort; severe arrhythmias; or ⬎1 mm of horizontal
or downward-sloping ST segment depression. Based on these criteria,
two subjects who had an ischemic response to exercise and two who
had an impaired chronotropic response (i.e., inability to achieve 80%
of the age-predicted maximal heart rate, defined as 220 beats/min
minus age) were excluded.
Exercise training program. All exercise training sessions were
supervised by an exercise physiologist and were conducted at the
Downloaded from jap.physiology.org on August 7, 2010
University of Tsukuba. In brief, a 10-min warm-up session was
conducted in the fitness studio, followed by aerobic exercise (running)
around the University of Tsukuba campus, and a 10-min cool-down
period, along with a predetermined set of stretching exercises for the
quadriceps, hamstrings, and gastrocnemius before and after each
session. The exercise intensity was based on the percentage of
maximal heart rate attained by each subject, which was determined
during the initial aerobic fitness test. Briefly, the exercise training
intensity calculated from the maximum heart rate achieved during the
maximal graded exercise test on a cycling ergometer was commenced
at a level prescribed between 50 and 60% of the maximal heart rate
and was gradually increased so that by week 4, the subjects were
exercising at 60 –70% of the maximum heart rate (⯝50% V̇O2 peak),
corresponding to their maximum heart rate, or 11–13 of Borg’s scale
(7) until the completion of the exercise program. Using heart rate
monitors, the target range of heart rate was monitored during each
exercise session. Both the day-by-day account of ambulation and
activity were assessed by a uniaxial accelerometry sensor (Lifecorder;
Suzuken). To estimate energy expenditure of exercise, heart rate was
monitored continuously during each training session by using a
telemetric heart rate monitor (RS 400; Polar Electro Accurex Plus).
Diet record. The participants were encouraged not to alter their
dietary intake during the course of the study to confirm only the
exercise effects. Every week, the subjects were instructed to complete
their dietary records, which were analyzed by the Tsukuba Health
Center dietitian, and were asked to maintain their pretraining diet.
Insulin resistance. A single bout of exercise has been shown to
improve insulin sensitivity, and these effects can persist for up to 48 h
after exercise (28, 35). Therefore, at 48 –50 h after the last bout of
exercise, we evaluated the insulin sensitivity from the plasma glucose
and serum insulin levels. The quantitative insulin sensitivity check
index (QUICKI), a surrogate measure of insulin resistance, is a simple
index that is based on the glucose and insulin levels in a fasting blood
sample (24, 29) and is calculated as follows:
QUICKI⫽1/{log [fasting insulin 共␮U/ml兲]
⫹ log [fasting glucose (mg/dl)]}
Blood pressure and biochemical analysis. Blood pressure was
measured after at least a 20-min rest period using a mercury manom-
eter. We calculated the average of two measurements separated by at
least a 3-min interval for each subject who lay bare-armed in a bed
with the back angulated at ⬃45° from the table and supported at the
level of the heart. Both systolic and diastolic blood pressure was
recorded.
www.jap.org
 EPICARDIAL FAT AND EXERCISE TRAINING
At baseline and after exercise, blood sampling was performed in
overnight-fasted participants sitting upright after blood pressure mea-
surement and a rest period of at least 20 –30 min. The fasting blood
samples were collected from the antecubital vein into tubes containing
either sodium fluoride/EDTA for glucose or into tubes containing no
additive for lipids and insulin. In brief, blood samples were put into
8-ml tubes containing thrombin- and heparin-neutralizing agents. The
tubes were immediately centrifuged at 3,000 rpm for 10 min at 4°C.
The blood in the 8-ml tubes was used for analyses of plasma
concentrations of free fatty acids, insulin, and lipids. Plasma TG
concentrations were determined by the enzymatic method by using a
TG kit, and plasma free fatty acids were measured by the colorimetric
method (25). Low-density lipoprotein (LDL)-cholesterol was calcu-
lated according to Friedewald’s formula (10). Serum high-sensitivity
C-reactive protein was determined by an immunonephelometric assay
(lipoprotein was determined by immunonephelometry). The inter- and
intra-assay coefficients of variation were ⬍5% for all blood parame-
ters.
Statistical procedures. All values are presented as means ⫾ SD.
The baseline data were compared with the data obtained after exercise
training by the paired t-test. The categorical data of the metabolic
syndrome were compared using a ␹2 test. The data were analyzed by
7
from 283 ⫾ 124 to 494 ⫾ 126 kcal/day due to the 3-mo aerobic
exercise program.
Twenty-four subjects completed the aerobic exercise train-
ing. Their average age was 49.4 ⫾ 9.6 yr and mean BMI was
30.4 ⫾ 3.4 kg/m2. Only one subject did not have abdominal
obesity (waist circumference ⬎ 88 cm, and visceral fat area ⬎
100 cm2), while 58% of the subjects (n ⫽ 14) had the
metabolic syndrome according to the criteria of the Japan
Society for the Study of Obesity. The number of individuals
with the metabolic syndrome significantly decreased to 42.3%
after the 3-mo exercise training program, suggesting that aer-
obic exercise training can improve the status of metabolic
factors in obese men as shown in Table 2. In addition, QUICKI
significantly increased after aerobic exercise training, suggest-
ing the amelioration of insulin resistance. However, the serum
C-reactive protein concentration did not change (1,872 ⫾
2,210 vs. 1,167 ⫾ 817 mg/l before and after the exercise
training, respectively; P ⫽ 0.094). The level of cardiovascular
fitness improved with an average 23.7% increase in V̇O2peak
after exercise training (28.4 ⫾ 7.2 vs. 34.0 ⫾ 6.2

Downloaded from jap.physiology.org on August 7, 2010

one-way ANOVA followed by Dunnett’s multiple comparison test.
Pearson’s correlation coefficient analysis was used to determine the
relationships between the variables. To determine the variables inde-
pendently associated with changes in the epicardial fat levels, a
stepwise multiple regression analysis was performed. The normality
of distribution of the variables was assessed using the Shapiro-Wilks
test, and they were used as dependent and independent variables. The
data were analyzed using the SPSS 13.0 version for Windows package
(SPSS, Chicago, IL). A statistically significant level of P ⬍ 0.05 was
chosen. Two-tailed P values have been used in the text.
RESULTS
Clinical characteristics of the study participants. The char-
acteristics of the participants who underwent exercise testing
and blood examination at baseline and after exercise training
are shown in Table 1. The total energy intake as assessed by
nutritionists before and after the exercise training was shown to
have decreased slightly from 2,237 ⫾ 422 to 2,180 ⫾ 444
kcal/day, although not statistically significant. Meanwhile, the
energy expenditure on physical activity increased significantly
ml䡠kg⫺1 䡠min⫺1 before and after exercise training, respec-
tively; P ⬍ 0.001) as a result of training. The anaerobic
threshold also increased significantly (17.7 ⫾ 3.9 vs. 19.3 ⫾
4.4 ml䡠kg⫺1 䡠min⫺1 before and after exercise training, respec-
tively; P ⫽ 0.002). Likewise, a significant decrease in the
resting heart rate (HRrest) was observed (69.9 ⫾ 13.3 vs.
64.8 ⫾ 7.9 beats/min before and after exercise training, respec-
tively; P ⬍ 0.001). However, the peak heart rate remained
unchanged (156 ⫾ 14 vs. 157 ⫾ 13 beats/min before and after
exercise training, respectively; P ⫽ 0.538).
Abdominal and epicardial fat tissue. To assess the reproduc-
ibility of the echocardiographic measurement of epicardial fat
thickness, 24 subjects were randomly selected for off-line
analysis by two observers who were unaware of metabolic and
clinical data. The intraclass correlation coefficient was 0.92
and the interclass correlation coefficient was 0.97, suggesting
an excellent reproducibility of this fat thickness. The changes
in the abdominal fat area as measured by computed axial
tomography showed that the subcutaneous and visceral fat had

Table 1. Anthropometric and dietary variables before and after the exercise training program
Variable Pretraining Posttraining %Change P

Age, yr 49.4⫾9.6
Body mass, kg 87.7⫾11.2 84.1⫾10.2 ⫺4.2⫾3.0 ⬍0.001
Body mass index, kg/m2 30.7⫾3.3 29.3⫾2.9 ⫺4.3⫾3.0 ⬍0.001
Waist, cm 103.0⫾7.8 98.4⫾6.9 ⫺4.4⫾2.6 ⬍0.001
Fat, % 33.3⫾3.8 31.0⫾4.5 ⫺6.8⫾5.7 ⬍0.001
Fat mass, kg 26.7⫾4.6 24.0⫾6.0 ⫺7.9⫾18.9 0.016
Body fat-free mass, kg 60.6⫾8.3 59.5⫾5.5 ⫺1.5⫾8.7 0.290
Systolic blood pressure, mmHg 142.8⫾20.0 139.2⫾16.4 ⫺2.2⫾5.0 0.028
Diastolic blood pressure, mmHg 95.4⫾14.0 92.5⫾13.0 ⫺2.8⫾7.5 0.062
V̇O2peak, ml 䡠 kg⫺1 䡠 min⫺1 28.4⫾7.2 34.3⫾5.6 20.5⫾12.2 ⬍0.001
Anaerobic threshold, ml 䡠 kg⫺1 䡠 min⫺1 17.7⫾3.9 19.3⫾4.4 9.4⫾13.4 0.002
Peak heart rate, beats/min 156⫾14 157⫾13 0.8⫾5.3 0.538
Resting heart rate, beats/min 70⫾13 65⫾8 ⫺6.1⫾8.1 0.005
Physical activity, kcal/day 283⫾124 494⫾126 70.8⫾54.1 ⬍0.001
Pedometer, step/day 7,650⫾2,598 10,570⫾2,086 48.7⫾38.3 ⬍0.001
Energy intake, kcal/day 2,196⫾412 2,096⫾305 ⫺2.3⫾18.0 0.205
Carbohydrate, g/day 291⫾75 275⫾56 ⫺3.1⫾17.0 0.126
Fat, g/day 62⫾19 62⫾14 ⫺0.1⫾19 0.973
Protein, g/day 85⫾20 84⫾20 0.4⫾18 0.735
Values are means ⫾ SD; n ⫽ 24 subjects. V̇O2peak, peak oxygen uptake.

J Appl Physiol • VOL 106 • JANUARY 2009 • www.jap.org

8 EPICARDIAL FAT AND EXERCISE TRAINING

Table 2. Blood parameters before and after the exercise training program
Variable Pretraining Posttraining %Change P

TC, mg/dl 234.2⫾39.9 208.8⫾44.2 ⫺11.2⫾6.8 ⬍0.001

HDLC, mg/dl 51.7⫾12.7 52.7⫾13.2 15.7⫾12.0 0.280
TG, mg/dl 193.1⫾118.0 126.0⫾55.1 ⫺26.0⫾27.2 0.001
LDLC, mg/dl 143.9⫾40.4 130.9⫾40.1 ⫺8.6⫾12.5 0.001
TC/HDLC ratio 4.77⫾1.33 4.10⫾1.06 ⫺12.8⫾8.7 ⬍0.001
TG/HDLC ratio 4.44⫾4.11 2.69⫾1.74 ⫺26.3⫾30.6 0.005
Apolipoprotein A-I, mg/dl 142.3⫾22.6 129.6⫾21.8 ⫺8.7⫾6.7 ⬍0.001
Apolipoprotein A-II, mg/dl 32.6⫾4.9 28.5⫾3.8 ⫺12.2⫾8.6 ⬍0.001
AST, IU/l 33.3⫾13.0 27.8⫾9.0 ⫺11.7⫾25.4 0.013
ALT, IU/l 51.7⫾32.0 36.9⫾19.3 ⫺19.3⫾38.6 0.006
␥-GTP, IU/l 60.8⫾39.0 47.7⫾33.5 ⫺15.8⫾41.2 ⬍0.001
Free fatty acids, meq/l 0.54⫾0.16 0.57⫾0.21 11.3⫾41.6 0.671
Fasting glucose, mg/dl 103.7⫾23.4 98.4⫾11.3 ⫺3.4⫾9.8 0.098
Fasting insulin, ␮U/ml 7.94⫾3.58 6.86⫾3.42 ⫺1.0⫾30.3 0.041
Insulin sensitivity, QUICKI 0.35⫾0.03 0.36⫾0.03 3.70⫾7.05 0.020
Log high-sensitivity CRP, mg/l 3.04⫾0.47 2.87⫾0.39 ⫺4.65⫾4.44 0.054
Metabolic syndrome,* % 57.7 42.3 ⫺26.7 0.033
Data are expressed as means ⫾ SD. TC, total cholesterol; HDLC, high-density lipoprotein cholesterol; TG, triglyceride; LDLC, low-density lipoprotein
cholesterol; AST, alanine aminotransferase; AST, aspartate aminotransferase; ␥-GTP, ␥-glutamyl transpeptidase; QUICKI, quantitative insulin sensitivity check

Downloaded from jap.physiology.org on August 7, 2010

index; CRP, C-reactive protein. Paired t-test for statistical differences except for metabolic syndrome, which was evaluated using a ␹2-test. *Metabolic syndrome
was assessed according to the criteria established by the Japan Society for the Study of Obesity.

decreased significantly with aerobic exercise training (subcu-
taneous fat: 234.6 ⫾ 74.0 vs. 194.1 ⫾ 58.9 cm2 before and
after exercise training, respectively; visceral fat: 197.1 ⫾ 61.9
vs. 165.7 ⫾ 57.0 cm2 before and after exercise training,
respectively; P ⬍ 0.001). Likewise, the epicardial fat thickness
as measured by M-mode echocardiography was significantly
decreased in our subjects (8.11 ⫾ 1.64 vs. 7.39 ⫾ 1.54 mm
before and after exercise training, respectively; P ⬍ 0.001), as
shown in Fig. 1.
The percent change of epicardial fat thickness (⫺8.61%)
was significantly higher compared with those of waist
(⫺4.4%), BMI (⫺4.3%), and body weight (⫺4.2%) of original
values after exercise training. In addition, percent changes in
the epicardial fat thickness were significantly different from
those of waist (P ⫽ 0.015), BMI (P ⫽ 0.013), and body weight
(P ⫽ 0.011). The abdominal fat and epicardial fat were
significantly decreased following aerobic exercise training in
obese people, as indicated in Fig. 2. We determined whether
the change in the epicardial fat thickness was related with the
change in the abdominal fat in obese men following the
exercise training. Pearson product-moment correlation analysis
indicated that the changes in the epicardial fat thickness were
significantly associated with the changes in the visceral fat
tissue with exercise training (r ⫽ 0.525; P ⫽ 0.008) as shown
in Fig. 3. The results showed that epicardial fat, as a form of
intra-abdominal visceral fat, reduced with a concomitant de-
crease in the abdominal visceral fat following aerobic exercise
training. To analyze the significant prerequisites that could
explain the changes (⌬) in the epicardial fat thickness as the
dependent variable, namely ⌬epicardial fat, a stepwise multiple

Fig. 1. Changes in epicardial fat thickness. Epicardial fat thickness was
measured before (Pretraining) and after the 12-wk exercise training program
(Posttraining). Values are means ⫾ SD and are representative of the 24
subjects.
Fig. 2. Percent changes in the subcutaneous, visceral, and epicardial fat tissue.
Subcutaneous, visceral, and epicardial fat tissues were measured before and
after the 12-wk exercise training intervention. Values are means ⫾ SE of the
percent changes in each fat tissue and are representative of the 24 subjects.
夹 Percent change in the subcutaneous, visceral, and epicardial fat thickness
was significantly lower compared with each initial value.

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 EPICARDIAL FAT AND EXERCISE TRAINING
Fig. 3. Correlation between the percent changes in visceral fat tissue and
epicardial fat thickness. Scatterplot depicts the relationship between the per-
cent changes in visceral fat and epicardial fat tissue after the 12-wk exercise
9
thickness in obese men can be reduced by exercise training.
Second, the percent change in epicardial fat thickness was
twice as high compared with those of the waist, BMI, and body
weight after exercise training. Third, reduction in the epicardial
fat thickness was accompanied by a decrease in the VAT.
Fourth, the change in VAT, SBP, and QUICKI were indepen-
dently related to the change in epicardial fat thickness.
In general, increased amount of abdominal fat contributes to
insulin resistance. More recently, it has been reported that VAT
loss after aerobic exercise training improves glucose metabo-
lism and is associated with the reversal of insulin resistance
(31). In present study, we found a significant association
between the epicardial fat thickness and QUICKI at baseline,
although the association was weaker than that reported in a
previous study (17) (r ⫽ ⫺0.429, P ⬍ 0.05). Thus increased
physical activity due to a single bout of exercise as a lifestyle
modification may improve insulin sensitivity, and weeks of
exercise for reduction in fat tissue in the compartments of
various organs in obese men.

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training program in 24 subjects.
regression analysis was performed with all other independent
variables. ⌬BMI, ⌬VAT, ⌬QUICKI, ⌬SBP, ⌬HRrest, ⌬TG/
HDL, ⌬apolipoprotein A-I, ⌬apolipoprotein A-II, and ⌬%fat
were used as independent variables. All variables were found
to show a normal distribution on assessment by the Shapiro-
Wilks test. As a result, ⌬VAT, ⌬SBP, and ⌬QUICKI were
independently related to ⌬epicardial fat (P ⬍ 0.05), as shown
in Table 3 while the other variables, including ⌬HRrest, ⌬TG/
HDL, ⌬apolipoprotein A-I, ⌬apolipoprotein A-II, and ⌬%fat,
were not entered into the analyses due to their nonsignificant
associations.
DISCUSSION
Although the metabolic alterations in epicardial adipose
tissue that signal progression of obesity to insulin resistance
remain unclear, the amount of epicardial fat tissue, which is a
recognized indicator of cardiac risk, is a potentially active
player in the development of an unfavorable metabolic risk
profile (16, 22). To the best of our knowledge, there are no data
on exercise training-induced changes in the epicardial fat tissue
in humans, although exercise has been shown to have effects
on visceral fat reduction in systematic reviews of clinical trials
(33) and other studies (37–38). In the present study, consider-
ing this factor, we investigated the effects of exercise training
on the epicardial fat thickness in obese men and tested the
hypothesis that a substantial reduction in the epicardial fat
thickness would be accompanied by a decrease in VAT. The
original finding of the present study is as follows. First, our
data demonstrated for the first time that the epicardial fat
It has been reported that BMI and VAT are strongly asso-
ciated with epicardial fat thickness (18). However, it is likely
that different types of intervention program affect the change in
the pattern of epicardial fat thickness. For instance, in a very
low-calorie-diet weight loss program, the epicardial fat thick-
ness, waist, BMI, and body weight values were 32%, 23%,
19%, and 20%, respectively, lower than the baseline values.
However, in this study, the exercise training program demon-
strated that the percent change in epicardial fat thickness
(⫺8.6%) was twice as high compared with the original values
of the waist (⫺4.4%), BMI (⫺4.3%), and body weight
(⫺4.2%) after exercise training; this suggested that exercise
training exhibits more percent reduction in epicardial fat thick-
ness compared with the above-mentioned adiposity indexes
such as the waist, BMI, and body weight.
Lipid accumulation within nonadipose tissues and organs
has been reported. A recent study showed that the accumula-
tion of TGs in the left ventricular myocardium, which is
strongly associated with epicardial fat deposition (r ⫽ 0.69),
was significantly increased in obese individuals rather than in
lean individuals (23). In addition, it has been reported that the
intervention program decreased the intracellular lipid contents
in hepatocytes and myocytes, i.e., a negative association be-
tween lipids and insulin sensitivity, in non-insulin-dependent
diabetes mellitus and obese subjects (40, 44). Taken together,
the ongoing accumulation of lipids in and around nonadipose
tissues and organs may implicate its association with a variety
of diseases such as metabolic and cardiovascular diseases.
There are regional heterogeneous differences in lipolytic
activity between the various adipose tissue depots in the body,
depending on anatomic location (3). For instance, the VAT

Table 3. Stepwise multiple linear regression analysis of obese subjects before and after the exercise training program
Dependent Variable Independent Variables ␤ ␤SE Standardized ␤ P Values Model r2

⌬EpiFat ⌬VAT 0.101 0.002 0.524 0.000 0.744

⌬SBP ⫺0.050 0.010 ⫺0.579 0.000
⌬QUICKI ⫺12.284 3.004 ⫺0.468 0.001
The stepwise multiple regression analysis using the change in epicardial fat thickness (⌬ EpiFat) as the dependent variable was performed to analyze the
significant predictors. BMI, body mass index; VAT, visceral adipose tissue; SBP, systolic blood pressure; HRrest, resting heart rate. ⌬BMI, ⌬VAT, ⌬SBP,
⌬QUICKI, ⌬HRrest, ⌬TG/HDL, ⌬apolipoprotein A-I, ⌬apolipoprotein A-II, and ⌬% fat were used as independent variables.

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10 EPICARDIAL FAT AND EXERCISE TRAINING
adipocytes are more sensitive to adrenergic stimulation than
abdominal subcutaneous adipocytes with a greater lipolytic
capacity and lesser antilipolytic action of insulin (13); on the
other hand, a clear dose-response relationship has been ob-
served between exercise amount and changes in VAT in a
prospective, randomized, controlled study (42), as well as in a
systemic review of clinical trials (33). Our present study did
not show a greater reduction in VAT in response to exercise
training, unlike the other studies (39). This difference may be
explained as follows. First, in the subjects’ characteristics,
there was a substantially higher variation of VAT distribution
at baseline. The lipolytic response during relative exercise
intensity seems to be different because of the difference in
obesity phenotype reported in our previous study (30). Second,
exercise training protocols of this study, in particular the
volume and intensity of exercise, was different from those in
previous intervention studies; these studies demonstrated that
high amount [equivalent to 20 miles/wk at vigorous intensity
(65– 80% V̇O2peak) (42) or exercise expenditure by 700 kcal/
day (37)] showed a preferentially reduced VAT, whereas low
amount [equivalent to 12 miles/wk of moderate-intensity ex-
ercise training (40 –55% V̇O2peak)] showed a reduction in sub-
cutaneous fat compared with VAT (42). Therefore, a study on
the relationship of exercise intensity with epicardial fat thick-
ness is warranted in the future.
Little is known on the effects of intervention program on the
distribution of epicardial fat tissue vs. VAT depot. We are
aware of two studies that used our same techniques; in these
studies, a 6-mo very low-calorie-diet (900 kcal/day) weight
loss program (⫺20 kg, on average) decreased epicardial fat
thickness (from 12.3 to 8.3 mm) in severely obese subjects
with BMI of 45 kg/m2 (20), and a weight loss program (⫺40
kg, on average) after bariatric surgery in severely obese pa-
tients with a BMI of 54 kg/m2 contributed to a decrease in the
epicardial adipose tissue, suggesting that weight loss alone
affects the reduction in epicardial fat thickness (49). Although
the present study provides a novel perception, i.e., decreased
epicardial fat thickness in response to exercise training in obese
men, it has some limitations. First, we did not have a control
group. As described earlier, weight loss alone reduces the
epicardial fat thickness. Therefore, study on the direct compar-
ison of effects of exercise training with and/or without weight
loss on epicardial fat tissue is required for further clarification.
However, for precise assessment of validity, the laboratory
investigators in the present study were blinded to the baseline
and follow-up (at the end of the study) recordings to minimize
the investigator bias. Second, the relatively small size of our
population sample might be concomitant with a type II error.
Taken together, further studies on the effects of exercise
training with and/or without weight loss involving a large
number of subjects are required to demonstrate the effective-
ness of exercise.
Along with clinical interest in epicardial adipose tissue (6 –7,
9, 16 –20), to date, many studies have focused on epicardial fat
tissue by measuring the length of the right ventricular epicar-
dial fat using echocardiography (2, 7, 18). Echocardiography
cannot be used for the quantification of epicardial fat tissue
because of its linear analysis, which may not reflect the
volumetric quantification of epicardial fat (20). However, mul-
tidetector CT provides epicardial fat distribution across the
various cardiac segments (1). Moreover, the assessment of
J Appl Physiol • VOL
epicardial fat volume summation of slices derived from three-
dimensional MRI (9) yields the values of volumetric epicardial
fat. More recently, cardiac multislice CT scans provide specific
values for quantifying the epicardial fat volume (11). There-
fore, further study will be required to assess quantitative
changes in the adipose tissue surrounding the heart after any
intervention program and exercise training.
The present study demonstrated that exercise training with-
out diet restriction causes a significant reduction in the epicar-
dial fat thickness along with a decrease in visceral fat, indicat-
ing an improvement in obesity-associated cardiovascular and
metabolic abnormalities; it also suggests important health ben-
efits of exercise training and reinforces the notion that exercise
training is a useful treatment strategy for obesity reduction.
ACKNOWLEDGMENTS
We are very grateful to Dr. Yasuhiro Nomata, Takayuki Endo, and Tetsuya
Akiba for outstanding work with the recruitment of subjects and scheduling of
the sessions and Yusuke Kato and Yuzou Koyama for assistance during data
collection. We also thank the nursing and dietary staff and the subjects for
Downloaded from jap.physiology.org on August 7, 2010
enthusiastic participation during the intervention period.
GRANTS
This research was supported by a Grant-in-Aid for Scientific Research (no.
20650112) from the Japan Ministry of Education, Culture, Sports, Science and
Technology.
REFERENCES
1. Abbara S, Desai JC, Cury RC, Butler J, Nieman K, Reddy V. Mapping
epicardial fat with multi-detector computed tomography to facilitate per-
cutaneous transepicardial arrhythmia ablation. Eur J Radiol 57: 417– 422,
2006.
2. Ahn SG, Lim HS, Joe DY, Kang SJ, Choi BJ, Choi SY, Yoon MH,
Hwang GS, Tahk SJ, Shin JH. Relationship of epicardial adipose tissue
by echocardiography to coronary artery disease. Heart 94: e7, 2008.
3. Arner P. Differences in lipolysis between human subcutaneous and
omental adipose tissues. Ann Med 27: 435– 438, 1995.
4. Beaver WL, Wasserman K, Whipp BJ. A new method for detecting
anaerobic threshold by gas exchange. J Appl Physiol 60: 2020 –2027,
1986.
5. Boden G, Shulman GI. Free fatty acids in obesity and type 2 diabetes:
defining their role in the development of insulin resistance and beta-cell
dysfunction. Eur J Clin Invest 32: 14 –23, 2002.
6. Borg E, Borg G. Perceived exertion: a note on “history” and methods.
Med Sci Sports 5: 90 –93, 1973.
7. Eroglu S, Sade LE, Yildirir A, Bal U, Ozbicer S, Ozgul AS, Bozbas H,
Aydinalp A, Muderrisoglu H. Epicardial adipose tissue thickness by
echocardiography is a marker for the presence and severity of coronary
artery disease. Nutr Metab Cardiovasc Dis August 19, 2008 [Epub ahead
of print].
8. Examination Committee of Criteria for “Obesity Disease” in Japan:
Japan society for the Study of Obesity. New criteria for “Obesity
disease” in Japan. Circ J 66: 987–992, 2002.
9. Flüchter S, Haghi D, Dinter D, Heberlein W, Kühl HP, Neff W,
Sueselbeck T, Borggrefe M, Papavassiliu T. Volumetric assessment of
epicardial adipose tissue with cardiovascular magnetic resonance imaging.
Obesity (Silver Spring) 15: 870 – 878, 2007.
10. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concen-
tration of low-density lipoprotein cholesterol in plasma, without use of the
preparative ultracentrifuge. Clin Chem 18: 499 –502, 1972.
11. Gorter PM, de Vos AM, van der Graaf Y, Stella PR, Doevendans PA,
Meijs MF, Prokop M, Visseren FL. Relation of epicardial and pericoro-
nary fat to coronary atherosclerosis and coronary artery calcium in patients
undergoing coronary angiography. Am J Cardiol 102: 380 –385, 2008.
12. Groop LC, Saloranta C, Shank M, Bonadonna RC, Ferrannini E,
DeFronzo RA. The role of free fatty acid metabolism in the pathogenesis
of insulin resistance in obesity and non-insulin-dependent diabetes melli-
tus. J Clin Endocrinol Metab 72: 96 –107, 1991.
106 • JANUARY 2009 • www.jap.org
 EPICARDIAL FAT AND EXERCISE TRAINING
13. Hellmér J, Marcus C, Sonnenfeld T, Arner P. Mechanisms for differ-
ences in lipolysis between human subcutaneous and omental fat cells.
J Clin Endocrinol Metab 75: 15–20, 1992.
14. Hu FB, Manson JE, Stampfer MJ, Colditz G, Liu S, Solomon CG,
Willett WC. Diet, lifestyle, and the risk of type 2 diabetes mellitus in
women. N Engl J Med 345: 790 –797, 2001.
15. Iacobellis G, Assael F, Ribaudo MC, Zappaterreno A, Alessi G, Di
Mario U, Leonetti F. Epicardial fat from echocardiography: a new
method for visceral adipose tissue prediction. Obes Res 11: 304 –310,
2003.
16. Iacobellis G, Corradi D, Sharma AM. Epicardial adipose tissue: ana-
tomic, biomolecular and clinical relationships with the heart. Nat Clin
Pract Cardiovasc Med 2: 536 –543, 2005.
17. Iacobellis G, Leonetti F. Epicardial adipose tissue and insulin resistance
in obese subjects. J Clin Endocrinol Metab 90: 6300 – 6302, 2005.
18. Iacobellis G, Ribaudo MC, Assael F, Vecci E, Tiberti C, Zappaterreno
A, Di Mario U, Leonetti F. Echocardiographic epicardial adipose tissue
is related to anthropometric and clinical parameters of metabolic syn-
drome: a new indicator of cardiovascular risk. J Clin Endocrinol Metab
88: 5163–5168, 2003.
19. Iacobellis G, Ribaudo MC, Zappaterreno A, Iannucci CV, Leonetti F.
Relation between epicardial adipose tissue and left ventricular mass. Am J
Cardiol 94: 1084 –1087, 2004.
20. Iacobellis G, Singh N, Wharton S, Sharma AM. Substantial changes in
epicardial fat thickness after weight loss in severely obese subjects.
Obesity (Silver Spring) 16: 1693–1697, 2008.
21. Jensen MD, Haymond MW, Rizza RA, Cryer PE, Miles JM. Influence
of body fat distribution on free fatty acid metabolism in obesity. J Clin
Invest 83: 1168 –1173, 1989.
22. Jeong JW, Jeong MH, Yun KH, Oh SK, Park EM, Kim YK, Rhee SJ,
Lee EM, Lee J, Yoo NJ, Kim NH, Park JC. Echocardiographic epicar-
dial fat thickness and coronary artery disease. Circ J 71: 536 –9, 2007.
23. Kankaanpää M, Lehto HR, Pärkkä JP, Komu M, Viljanen A, Fer-
rannini E, Knuuti J, Nuutila P, Parkkola R, Iozzo P. Myocardial
triglyceride content and epicardial fat mass in human obesity: relationship
to left ventricular function and serum free fatty acid levels. J Clin
Endocrinol Metab 91: 4689 – 4695, 2006.
24. Katz A, Nambi SS, Mather K, Baron AD, Follmann DA, Sullivan G,
Quon MJ. Quantitative insulin sensitivity check index: a simple, accurate
method for assessing insulin sensitivity in humans. J Clin Endocrinol
Metab 85: 2402–2410, 2000.
25. Martin ML, Jensen MD. Effects of body fat distribution on regional
lipolysis in obesity. J Clin Invest 88: 609 – 613, 1991.
26. Mathieu P, Pibarot P, Larose E, Poirier P, Marette A, Després JP.
Visceral obesity and the heart. Int J Biochem Cell Biol 40: 821– 836, 2008.
27. McGarry JD. Banting lecture 2001: dysregulation of fatty acid metabo-
lism in the etiology of type 2 diabetes. Diabetes 51: 7–18, 2001.
28. Mikines KJ, Sonne B, Farrell PA, Tronier B, Galbo H. Effect of
physical exercise on sensitivity and responsiveness to insulin in humans.
Am J Physiol Endocrinol Metab 254: E248 –E259, 1988.
29. Muniyappa R, Lee S, Chen H, Quon MJ. Current approaches for
assessing insulin sensitivity and resistance in vivo: advantages, limita-
tions, and appropriate usage. Am J Physiol Endocrinol Metab 294: E15–
E26, 2008.
30. Numao S, Hayashi Y, Katayama Y, Matsuo T, Tomita T, Ohkawara
K, Nakata Y, Tanaka K. Effects of obesity phenotype on fat metabolism
in obese men during endurance exercise. Int J Obes (Lond) 30: 1189 –
1196, 2006.
31. O’Leary VB, Marchetti CM, Krishnan RK, Stetzer BP, Gonzalez F,
Kirwan JP. Exercise-induced reversal of insulin resistance in obese
elderly is associated with reduced visceral fat. J Appl Physiol 100:
1584 –1589, 2006.
J Appl Physiol • VOL 106 • JANUARY 2009 •
11
32. Ogden CL, Carroll MD, Curtin LR, McDowell MA, Tabak CJ, Flegal
KM. Prevalence of overweight and obesity in the United States, 1999 –
2004. JAMA 295: 1549 –1555, 2006.
33. Ohkawara K, Tanaka S, Miyachi M, Ishikawa-Takata K, Tabata I. A
dose-response relation between aerobic exercise and visceral fat reduction:
systematic review of clinical trials. Int J Obes (Lond) 31: 1786 –1797,
2007.
34. Okura T, Nakata Y, Tanaka K. Effects of exercise intensity on physical
fitness and risk factors for coronary heart disease. Obes Res 11: 1131–
1139, 2003.
35. Perseghin G, Price TB, Petersen KF, Roden M, Cline GW, Gerow K,
Rothman DL, Shulman GI. Increased glucose transport-phosphorylation
and muscle glycogen synthesis after exercise training in insulin-resistant
subjects. N Engl J Med 335: 1357–1362, 1996.
36. Ritchie SA, Connell JM. The link between abdominal obesity, metabolic
syndrome and cardiovascular disease. Nutr Metab Cardiovasc Dis 17:
319 –326, 2007.
37. Ross R, Dagnone D, Jones PJ, Smith H, Paddags A, Hudson R,
Janssen I. Reduction in obesity and related comorbid conditions after
diet-induced weight loss or exercise-induced weight loss in men. A
randomized, controlled trial. Ann Intern Med 133: 92–103, 2000.
38. Ross R, Freeman JA, Janssen I. Exercise alone is an effective strategy
for reducing obesity and related comorbidities. Exerc Sport Sci Rev 28:
165–170, 2000.
Downloaded from jap.physiology.org on August 7, 2010
39. Ross R, Janssen I. Is abdominal fat preferentially reduced in response to
exercise-induced weight loss? Med Sci Sports Exerc 31: S568 –S572,
1999.
40. Ross R, Janssen I. Physical activity, total and regional obesity: dose-
response considerations. Med Sci Sports Exerc 33: S521–S527, 2001.
41. Sato F, Tamura Y, Watada H, Kumashiro N, Igarashi Y, Uchino H,
Maehara T, Kyogoku S, Sunayama S, Sato H, Hirose T, Tanaka Y,
Kawamori R. Effects of diet-induced moderate weight reduction on
intrahepatic and intramyocellular triglycerides and glucose metabolism in
obese subjects. J Clin Endocrinol Metab 92: 3326 –3329, 2007.
42. Slentz CA, Aiken LB, Houmard JA, Bales CW, Johnson JL, Tanner CJ,
Duscha BD, Kraus WE. Inactivity, exercise, and visceral fat. STRRIDE: a
randomized, controlled study of exercise intensity and amount. J Appl Physiol
99: 1613–1618, 2005.
43. Stannard SR, Johnson NA. Insulin resistance and elevated triglyceride in
muscle: more important for survival than “thrifty” genes? J Physiol 554:
595– 607, 2004.
44. Tanaka K, Takeshima N, Kato T, Niihata S, Ueda K. Critical deter-
minants of endurance performance in middle-aged and elderly endurance
runners with heterogeneous training habits. Eur J Appl Physiol Occup
Physiol 59: 443– 449, 1990.
45. Thomas EL, Hamilton G, Patel N, O’Dwyer R, Dore CJ, Goldin RD,
Bell JD, Taylor-Robinson SD. Hepatic triglyceride content and its
relation to body adiposity: a magnetic resonance imaging and proton
magnetic resonance spectroscopy study. Gut 54: 122–127, 2005.
46. Tuomilehto J, Lindström J, Eriksson JG, Valle TT, Hämäläinen H,
Ilanne-Parikka P, Keinänen-Kiukaanniemi S, Laakso M, Louheranta
A, Rastas M, Salminen V, Uusitupa M; Finnish Diabetes Prevention
Study Group. Prevention of type 2 diabetes mellitus by changes in
lifestyle among subjects with impaired glucose tolerance. N Engl J Med
344: 1343–1350, 2001.
47. Tylleskär K, Tuvemo T, Gustafsson J. Diabetes control deteriorates in
girls at cessation of growth: relationship with body mass index. Diabet
Med 18: 811– 815, 2001.
48. Wasserman K. The anaerobic threshold measurement to evaluate exercise
performance. Am Rev Respir Dis 129: S35–S40, 1984.
49. Willens HJ, Byers P, Chirinos JA, Labrador E, Hare JM, de March-
ena E. Effects of weight loss after bariatric surgery on epicardial fat
measured using echocardiography. Am J Cardiol 99: 1242–1245, 2007.
www.jap.org