Articles in PresS. J Appl Physiol (October 16, 2008). doi:10.1152/japplphysiol.90756.2008
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Aerobic Exercise Training Reduces Epicardial Fat in Obese Men
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Maeng-Kyu Kim1, Tsugio Tomita2, Mi-Ji Kim1, Hiroyuki Sasai1, Seiji Maeda1, Kiyoji
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Tanaka1
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Tennodai, Tsukuba, Ibaraki 305-8577 Japan
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Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1
Department of Radiation, Higashi Toride Hospital, Ibaraki, Japan
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ADDRESS CORRESPONDENCE TO:
Kiyoji Tanaka, PhD
Department of Sports Medicine for Health and Disease
University of Tsukuba
Tsukuba, Ibaraki 305-8577 Japan
Tel: +81-29-853-2655
Fax: +81-29-853-2986
E-mail: [email protected]
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Running title: Epicardial fat and exercise training
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Copyright © 2008 by the American Physiological Society.
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ABSTRACT
The purpose of this study was to determine the effects of exercise training on
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ventricular epicardial fat thickness in obese men and to investigate the relationship
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between the changes in epicardial fat thickness to the abdominal fat tissue following
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exercise training. Twenty-four obese middle-aged men (age, 49.4 ± 9.6 years; weight,
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87.7 ± 11.2 kg; body mass index (BMI), 30.7 ± 3.3; peak oxygen consumption, 28.4 ±
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7.2 mL/kg/min; mean ± SD) participated in this study. Each participant completed a
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12-week supervised exercise training program (60–70% of the maximal heart rate; 60
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min/d; 3 d/week) and underwent a transthoracic echocardiography. The epicardial fat
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thickness on the free wall of the right ventricle was measured from both parasternal
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long- and short-axis views. The visceral adipose tissue (VAT) and subcutaneous adipose
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tissues were measured by computed tomography. Following exercise training, the
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epicardial fat thickness was significantly decreased (P < 0.001). The percentage change
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of epicardial fat thickness was twice as high compared with those of waist, BMI, and
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body weight of original values (P <0.05). There was a significant relationship (r = 0.525,
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P = 0.008) between changes in the epicardial fat thickness and visceral adipose tissue
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with exercise training. Stepwise multiple regression analysis revealed that ΔVAT, ΔSBP,
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and ΔQUICKI were independently related to Δepicardial fat thickness (P <0.05). The
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ventricular epicardial fat thickness is reduced significantly after aerobic exercise
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training and is associated with a decrease in VAT. These results suggest that aerobic
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exercise training may be an effective nonpharmacological strategy for decreasing the
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ventricular epicardial fat thickness and visceral fat area in obese middle-aged men.
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Keywords: abdominal adiposity; systolic blood pressure; insulin resistance
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INTRODUCTION
The incidence and prevalence of obesity are significantly increasing all over
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the world, and obesity represents a major health hazard due to the independent risks that
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are directly related to increased body mass index per se in addition to the associated
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potential risks for the development of diabetes, dyslipidemia, and hypertension (32).
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Emerging evidence has shown that in obesity, excessive fat accumulation is ubiquitous
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in the liver (45), abdominal viscera and subcutaneous tissues (37), and within myocytes
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(43), all of which lead to worsening of insulin sensitivity in the general population and
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impaired metabolic control in diabetic patients (47). Besides the above sites of adipose
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accumulation, epicardial adipose tissue has been potentially recognized as a marker of
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cardiac risk and of the development of an unfavorable metabolic risk profile (16, 18).
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Echocadiographically measured epicardial fat on the free wall of right ventricle has
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been shown to be true visceral fat with all the characteristics of highly insulin-resistant
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tissues (18) and is related to an increase in the left ventricular mass (19). Therefore,
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effective treatments are needed to decrease the amount of epicardial fat in the obese.
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Considering this factor, a recent study used a recently validated echocardiographic
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measure and reported that weight loss after bariatric surgery in severely obese patients
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contributed to a decrease in the epicardial adipose tissue (49). More recently, very low
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calorie diet of weight loss program decreased epicardial fat thickness, which is
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associated with changes in fat distribution in severely obese subjects (20).
Exercise is well known as the cornerstone treatment for obesity-related
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metabolic complications, including insulin resistance, hypertension, impaired glucose
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tolerance or diabetes, hyperinsulinemia, and dyslipidemia that are characterized by
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elevated adipose accumulation (14, 46). Physical activity is known as a common
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prescription to reduce abdominal adipose deposition and obesity (37–38) and to
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improve glucose tolerance and lipid metabolism through its acute and chronic effects,
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and physical activity has been associated with a reduction in abdominal and visceral fat
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(31, 40); surprisingly however, to the best of our knowledge, only a few human studies
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have been conducted to determine whether exercise training changes the epicardial fat
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thickness.
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The purpose of the present study was, therefore, to determine whether aerobic
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exercise training without diet restriction changes the ventricular epicardial fat thickness
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and whether the changes in the abdominal visceral fat deposits are associated with the
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epicardial fat thickness during exercise training in middle-aged obese men.
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MATERIALS AND METHODS
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Participants
The subjects were recruited through advertisements in local newspapers. In
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general, the volunteers were healthy, were not consuming any medication known to alter
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glucose and lipid metabolism, and were reportedly free of any diagnosed cardiovascular
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disease, any contraindication to exercise, or any known metabolic disorder. The nature,
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purpose, and potential risks of the study were explained to all the subjects, and
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voluntary informed written consent was obtained from all subjects before participation
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in the study. This study was conducted in accordance with the guidelines proposed in
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The Declaration of Helsinki and was approved by the Higashi Toride hospital, and the
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study protocol was reviewed and approved by the Ethics Committee, University of
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Tsukuba, Japan. The MetSyn was defined according to the ‘the criteria of Japan Society
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for the Study Obesity (8) based on the presence of 100 cm2 of visceral fat area
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corresponding to waist circumference of 85 cm plus 2 or more co-morbidities consisting
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of 1) fasting glucose level ≥110 mg/dl, 2) systolic blood pressure ≥130 mm Hg and/or
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diastolic blood pressure ≥ 85 mm Hg, and 3) triglyceride level ≥ 150 mg/dl, and/or high
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density lipoprotein level < 40 mg/dl.
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Anthropometric measurements
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Body height was measured to the nearest 0.1 cm using a wall-mounted
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stadiometer (TBF-215; Tanita, Tokyo, Japan), and body weight was measured to the
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nearest 0.01 kg using calibrated electronic digital scales (TBF-215; Tanita, Tokyo,
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Japan) in barefoot subjects. Body mass index was calculated by dividing the weight (in
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kilograms) by the square of the height (square meters). Waist circumference was
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measured at the level of the umbilicus in lightly clothed participants in the standing
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position. The mean of 2 consecutive records was used as the measured value. Dual
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energy X-ray absorptiometry (DXA) was performed using a Lunar (software version
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1.3Z, DPX-L; Lunar, Madison, WI) to evaluate body composition, which was assumed
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to consist of fat mass and fat- and bone-free mass, as previously described (34). The
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pixels of soft tissue were used to calculate the ratio of mass attenuation coefficients at
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40 to 50 keV (low energy) and 80 to 100 keV (high energy). The subjects were made to
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lie supine with arms and legs at their sides during the 15-min scan; radiation exposure
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was < 7 μSv. All the scans were performed by the same operator, and daily quality
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assurance tests were performed according to the manufacturer’s directions. It places low
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demands on the subjects’ performance, and it is, therefore, the most convenient in the
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obese as well as elderly individuals. In the second measurement session, abdominal
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visceral fat and subcutaneous fat area were measured using computed tomography (CT)
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scans (SOMATOM AR.C; Siemens, Germany) set at 110 kVp and 50 mA. A single
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5-mm scan with a scanning time of 5 s was obtained, centered at the level of the
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umbilicus (fourth and fifth lumbar vertebrae) in the supine position with the
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participants’ arms extended above the head during the measurements. The images were
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digitized by optical density to separate the bone, muscle, and fat compartments. The
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visceral fat and subcutaneous fat area were calculated using a computer software
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program (Fat Scan; N2 system, Osaka, Japan), as described previously (30, 34). The
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measurement sessions were separated by approximately 1–2 d, dependent on the
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participant’s schedule and the availability of CT.
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Clinical assessment of epicardial adipose tissue
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For direct assessment of the epicardial adipose tissue, each participant
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underwent echocardiography as proposed by Iacobellis et al. (15, 18). With the subjects
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in
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echocardiography was performed using an Envisor C, Philips with a 2.5-MHz
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transducer. The largest dimension of this space was in the end-diastolic period and was
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measured from the trailing edge to the leading edge on the free wall of the right
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ventricle; this measurement was considered as the maximum epicardial fat thickness in
the
left
lateral
decubitus
position,
two-dimensionally
guided
M-mode
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2 standard echocardiographic views, namely the parasternal long-axis and short-axis
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views, and an average of the measurements on both views was obtained for offline
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analysis of the recorded videotape. To decrease the variability, 3 cardiac cycles were
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read and measured in the end-diastolic period of the right ventricle. At the analysis
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(before and after the exercise training program), research personnel were blinded to the
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baseline test results in order to minimize observation bias according to a previously
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described study; this was necessary because epicardial fat thickness was being carefully
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considered in relation to the degree of weight loss (20, 49).
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Anaerobic threshold and maximal aerobic capacity
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The subjects underwent a maximal graded exercise test on a cycling ergometer
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(818E; Monark, Stockholm, Sweden) for evaluation of cardiovascular function and
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simultaneous determination of the individual’s peak oxygen uptake (VO2) and anaerobic
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threshold (AT). Following a 2-min warm-up at 0 watt (W), the exercise was started at a
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workload of 15 W that was increased every 1 min by another 15 W until volitional
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exhaustion. During the test, ventilation and expired gases were measured using an
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automated gas exchange measuring system (Oxycon α system; Mijnhardt, Breda, The
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Netherlands), and the heart rate was constantly observed at rest and during the exercise
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and recovery periods using an ECG monitor (Dyna Scope; Fukudadenshi, Tokyo, Japan).
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AT, a discriminatory marker between cardiovascular and pulmonary limitations to
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exercise (48), was determined from Vslope-AT, which was plotted using the v-slope
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technique as described in an earlier study (4). The VCO2 versus VO2 curve was divided
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into 2 regions, each of which was fitted by linear regression, and the intersection
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between the 2 regression lines was regarded as the Vslope-AT. The software of the
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Oxycon equipment automatically established the regression lines and their crossing
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points. The highest oxygen uptake achieved over 30 s was determined as peak VO2. The
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peak VO2 was referred to the criteria described by Tanaka et al. (44). Exercise testing
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was discontinued in case of the following reasons: perceived exertion rating, > 18;
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achievement of > 90% of the age-predicted maximal heart rate or extreme fatigue such
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that pedaling on the bicycle was not possible; typical chest discomfort; severe
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arrhythmias; or > 1 mm of horizontal or downward-sloping ST segment depression.
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Based on these criteria, 2 subjects who had an ischemic response to exercise and 2 who
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had an impaired chronotropic response (i.e., inability to achieve 80% of the
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age-predicted maximal heart rate, defined as 220 beats/min minus age) were excluded.
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Exercise training program
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All exercise training sessions were supervised by an exercise physiologist and
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were conducted at the University of Tsukuba. In brief, a 10-min warm-up session was
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conducted in the fitness studio, followed by aerobic exercise (running) around the
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University of Tsukuba campus, and a 10-min cool-down period, along with a
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predetermined set of stretching exercises for the quadriceps, hamstrings, and
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gastrocnemius before and after each session. The exercise intensity was based on the
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percentage of maximal heart rate attained by each subject, which was determined during
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the initial aerobic fitness test. Briefly, the exercise training intensity calculated from the
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maximum heart rate achieved during the maximal graded exercise test on a cycling
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ergometer was commenced at a level prescribed between 50–60% of the maximal heart
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rate and was gradually increased so that by week 4, the subjects were exercising at
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60–70 % of the maximum heart rate (⋍50% VO2max), corresponding to their maximum
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heart rate, or 11–13 of Borg’s scale (7) until the completion of the exercise program.
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Using heart rate monitors, the target range of heart rate was monitored during each
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exercise session. The day-by-day account of ambulation activity and was assessed by
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both a uniaxial accelerometry sensor (Lifecorder; Suzuken Co. Ltd, Japan). To estimate
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energy expenditure of exercise, heart rate was monitored continuously during each
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training session by suing a telemetric heart rate monitor (RS 400; Polar electro Accurex
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Plus, Japan).
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Diet record
The participants were encouraged not to alter their dietary intake during the
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course of the study in order to confirm only the exercise effects. Every week, the
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subjects were instructed to complete their dietary records, which were analyzed by the
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Tsukuba Health Center dietitian, and were asked to maintain their pre-training diet.
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Insulin resistance
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A single bout of exercise has been shown to improve insulin sensitivity, and
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these effects can persist for up to 48 h after exercise (28, 35). Therefore, at 48~50 h
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after the last bout of exercise, we evaluated the insulin sensitivity from the plasma
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glucose and serum insulin levels. The quantitative insulin sensitivity check index
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(QUICKI), a surrogate measure of insulin resistance, is a simple index that is based on
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the glucose and insulin levels in a fasting blood sample (24, 29) and is calculated as
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follows.
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QUICKI = 1/[log (fasting insulin, μU/mL) + log (fasting glucose, mg/dL)]
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Blood pressure and biochemical analysis
Blood pressure was measured after at least a 20-min rest period using a
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mercury manometer. We calculated the average of 2 measurements separated by at least
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a 3-min interval for each subject who lay bare-armed in a bed with the back angulated at
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approximately 45°from the table and supported at the level of the heart. Both systolic
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and diastolic blood pressure was recorded.
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At baseline and after exercise, blood sampling was performed in overnight-fasted
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participants sitting upright after blood pressure measurement and a rest period of at least
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20–30 min. The fasting blood samples were collected from the antecubital vein into
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tubes containing either sodium fluoride/ ethylenediaminetetraacetic acid (EDTA) for
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glucose or into tubes containing no additive for lipids and insulin. In brief, blood
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samples were put into 8-mL tubes containing thrombin- and heparin-neutralizing agents.
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The tubes were immediately centrifuged at 3000 rpm for 10 min at 4℃. The blood in
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the 8-mL tubes was used for analyses of plasma concentrations of FFA, insulin, and
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lipids. Plasma triglyceride concentrations were determined by the enzymatic method by
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using a TG kit, and plasma NEFA was measured by the colorimetric method (25).
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LDL-cholesterol was calculated according to Friedewald’s formula (10). Serum
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high-sensitivity CRP was determined by an immunonephelometric assay (lipoprotein
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was determined by immunonephelometry). The inter- and intra-assay coefficients of
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variation were <5% for all blood parameters.
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Statistical procedures
All values are presented as the mean ± SD. The baseline data were compared
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with the data obtained after exercise training by the paired t-test. The categorical data of
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the metabolic syndrome were compared using a χ2 test. The data were analyzed by
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one-way analysis of variance followed by Dunnett’s multiple comparison test. Pearson’s
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correlation coefficient analysis was used to determine the relationships between the
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variables. To determine the variables independently associated with changes in the
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epicardial fat levels, a stepwise multiple regression analysis was performed. The
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normality of distribution of the variables was assessed using the Shapiro-Wilks test, and
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they were used as dependent and independent variables. The data were analyzed using
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the SPSS 13.0 version for Windows package (SPSS Inc., Chicago, IL). A statistically
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significant level of P < 0.05 was chosen. Two-tailed P values have been used in the text.
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Results
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Clinical characteristics of the study participants
The characteristics of the participants who underwent exercise testing and
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blood examination at baseline and after exercise training are shown in Table 1. The total
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energy intake as assessed by nutritionists before and after the exercise training was
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shown to have decreased slightly from 2237 ± 422 to 2180 ± 444 kcal/d, although not
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statistically significant. Meanwhile, the energy expenditure on physical activity
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increased significantly from 283 ± 124 to 494 ± 126 kcal/d due to the 3-month aerobic
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exercise program.
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Twenty-four subjects completed the aerobic exercise training. Their average age was
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49.4 ± 9.6 years and mean BMI was 30.4 ± 3.4 kg/m2. Only 1 subject did not have
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abdominal obesity (waist circumference, >88 cm and visceral fat area, >100 cm2), while
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58% of the subjects (n = 14) had the metabolic syndrome according to the criteria of the
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Japan Society for the Study of Obesity. The number of individuals with the metabolic
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syndrome significantly decreased to 42.3% after the 3-month exercise training program,
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suggesting that aerobic exercise training can improve the status of metabolic factors in
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obese men as shown in Table 2. In addition, QUICKI significantly increased after
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aerobic exercise training, suggesting the amelioration of insulin resistance. However,
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the serum C-reactive protein concentration did not change (1872 ± 2210 vs. 1167 ± 817
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mg/L before and after the exercise training, respectively; P = 0.094). The level of
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cardiovascular fitness improved with an average 23.7% increase in VO2peak after
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exercise training (28.4 ± 7.2 vs. 34.0 ± 6.2 ml·kg–1·min–1 before and after exercise
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training, respectively; P < 0.001) as a result of training. The anaerobic threshold also
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increased significantly (17.7 ± 3.9 vs. 19.3 ± 4.4 ml·kg–1·min–1 before and after exercise
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training, respectively; P = 0.002). Likewise, a significant decrease in the resting heart
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rate was observed (69.9 ± 13.3 vs. 64.8 ± 7.9 beats/min before and after exercise
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training, respectively; P < 0.001). However, the peak heart rate remained unchanged
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(156 ±14 vs. 157 ±13 beats/min before and after exercise training, respectively; P =
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0.538).
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Abdominal and epicardial fat tissue
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To assess the reproducibility of the echocardiographic measurement of
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epicardial fat thickness, 24 subjects were randomly selected for off-line analysis by two
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observers who were unaware of metabolic and clinical data. The intraclass correlation
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coefficient was 0.92 and the interclass correlation coefficient was 0.97, suggesting an
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excellent reproducibility of this fat thickness. The changes in the abdominal fat area as
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measured by computed axial tomography showed that the subcutaneous and visceral fat
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had decreased significantly with aerobic exercise training (subcutaneous fat: 234.6 ±
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74.0 vs. 194.1 ± 58.9 cm2 before and after exercise training, respectively; visceral fat:
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197.1 ± 61.9 vs. 165.7 ± 57.0 cm2 before and after exercise training, respectively; P <
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0.001).
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echocardiography was significantly decreased in our subjects (8.11 ± 1.64 vs. 7.39 ±
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1.54 mm before and after exercise training, respectively; P < 0.001), as shown in Fig 1.
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The percentage change of epicardial fat thickness (–8.61%) was significantly higher
9
compared with those of waist (–4.4%), BMI (–4.3%), and body weight (–4.2%) of
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original values after exercise training. In addition, percentage changes in the epicardial
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fat thickness were significantly different from those of waist (P = 0.015), BMI (P =
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0.013), and body weight (P = 0.011). The abdominal fat and epicardial fat were
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significantly decreased following aerobic exercise training in obese people, as indicated
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in Fig 2. We determined whether the change in the epicardial fat thickness was related
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with the change in the abdominal fat in obese men following the exercise training.
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Pearson product-moment correlation analysis indicated that the changes in the epicardial
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fat thickness were significantly associated with the changes in the visceral fat tissue
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with exercise training (r = 0.525; P = 0.008) as shown in Fig 3. The results showed that
Likewise,
the
epicardial
fat
thickness
as
measured
by
M-mode
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epicardial fat, as a form of intraabdominal visceral fat, reduced with a concomitant
2
decrease in the abdominal visceral fat following aerobic exercise training. In order to
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analyze the significant prerequisites that could explain the changes in the epicardial fat
4
thickness (Δepicardial fat) as the dependent variable, namely Δepicardial fat, a stepwise
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multiple regression analysis was performed with all other independent variables. ΔBMI,
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ΔVFA, ΔQUICKI, ΔSBP, ΔrestHR, ΔTG/HDL, Δapolipoprotein A-Ι, Δapolipoprotein
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A-Ⅱ, and Δ%fat were used as independent variables. All variables were found to show
8
a normal distribution on assessment by the Shapiro-Wilks test. As a result, ΔVFA, ΔSBP,
9
and ΔQUICKI were independently related to Δepicardial fat (P < 0.05), as shown in
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Table 3, while the other variables, including ΔrestHR, ΔTG/HDL, Δapolipoprotein A-Ι,
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Δapolipoprotein A-Ⅱ, and Δ%fat, were not entered into the analyses due to their
12
non-significant associations.
13
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Discussion
Although the metabolic alterations in epicardial adipose tissue that signal
3
progression of obesity to insulin resistance remain unclear, the amount of epicardial fat
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tissue, which is a recognized indicator of cardiac risk, is a potentially active player in
5
the development of an unfavorable metabolic risk profile (16, 22). To the best of our
6
knowledge, there are no data on exercise training-induced changes in the epicardial fat
7
tissue in humans, although exercise has been shown to have effects on visceral fat
8
reduction in systematic reviews of clinical trials (33) and other studies (37–38). In the
9
current study, considering this factor, we investigated the effects of exercise training on
10
the epicardial fat thickness in obese men and tested the hypothesis that a substantial
11
reduction in the epicardial fat thickness would be accompanied by a decrease in VFA.
12
The original finding of the present study is as follows. First, our data demonstrated for
13
the first time that the epicardial fat thickness in obese men can be reduced by exercise
14
training. Second, the percentage change in epicardial fat thickness was twice as high
15
compared with those of the waist, BMI, and body weight after exercise training. Third,
16
reduction in the epicardial fat thickness was accompanied by a decrease in the VFA.
17
Fourth, the change in VAT, SBP, and QUICKI were independently related to the change
18
in epicardial fat thickness.
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In general, increased amount of abdominal fat contributes to insulin resistance.
2
More recently, it has been reported that VFA loss after aerobic exercise training
3
improves glucose metabolism and is associated with the reversal of insulin resistance
4
(31). In present study, we found a significant association between the epicardial fat
5
thickness and QUICKI at baseline, although the association was weaker than that
6
reported in a previous study (17) (r = –0.429, P < 0.05). Thus, increased physical
7
activity due to a single bout of exercise as a lifestyle modification may improve insulin
8
sensitivity and the weeks of exercise for reduction in fat tissue in the compartments of
9
various organs in obese men.
10
It has been reported that BMI and VAT are strongly associated with epicardial
11
fat thickness (18). However, it is likely that different types of intervention program
12
affect the change in the pattern of epicardial fat thickness. For instance, in a very low
13
calorie diet, weight loss program, the epicardial fat thickness, waist, BMI, and body
14
weight values were 32%, 23%, 19%, and 20%, respectively, lower than the baseline
15
values. However, in this study, the exercise training program demonstrated that the
16
percentage change in epicardial fat thickness (–8.6%) was twice as high compared to the
17
original values of the waist (–4.4%), BMI (–4.3%), and body weight (–4.2%) after
18
exercise training; this suggested that exercise training exhibits more percentage
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reduction in epicardial fat thickness compared to the abovementioned adiposity index
2
such as the waist, BMI, and body weight.
Lipid accumulation within nonadipose tissues and organs has been reported. A
4
recent study showed that the accumulation of triglycerides in the left ventricular
5
myocardium, which is strongly associated with epicardial fat deposition (r = 0.69), was
6
significantly increased in obese individuals rather than in lean individuals (23). In
7
addition, it has been reported that the intervention program decreased the intracellular
8
lipid contents in hepatocytes and myocytes, i.e., a negative association between lipids
9
and insulin sensitivity, in NIDDM and obese subjects (40, 44). Taken together, the
10
ongoing accumulation of lipids in and around nonadipose tissues and organs may
11
implicate its association with a variety of diseases such as metabolic and cardiovascular
12
diseases.
13
There are regional heterogeneous differences in lipolytic activity between the
14
various adipose tissue depots in the body, depending on anatomical location (3). For
15
instance, the VAT adipocytes are more sensitive to adrenergic stimulation than
16
abdominal subcutaneous adipocytes with a greater lipolytic capacity and lesser
17
antilipolytic action of insulin (13); on the other hand, a clear dose-response relationship
18
has been observed between exercise amount and changes in VAT in a prospective,
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randomized, controlled study (42) as well as in a systemic review of clinical trials (33).
2
Our present study did not show a greater reduction in VAT in response to exercise
3
training, unlike the other studies (39). This difference may be explained as follows. First,
4
in the subjects’ characteristics, there was a substantially higher variation of VAT
5
distribution at baseline. The lipolytic response during relative exercise intensity seems
6
to be different because of the difference in obesity phenotype reported in our previous
7
study (30). Second, exercise training protocols of this study, in particular the volume
8
and intensity of exercise, was different from those in previous intervention studies;
9
these studies demonstrated that high amount (equivalent to 20 miles per week)/vigorous
10
．
intensity (65–80% peak VO2) (42) or exercise expenditure by 700 kcal per day (37)
11
showed a preferentially reduced VAT, whereas low amount (equivalent to 12 miles per
12
．
week)/moderate intensity exercise training (40–55% peak VO2) showed a reduction in
13
subcutaneous fat compared to VAT (42). Therefore, the study on the relationship of
14
exercise intensity with epicardial fat thickness is required in the future.
15
Little is known on the effects of intervention program on the distribution of
16
epicardial fat tissue vs. VAT depot. We are aware of two studies that used our same
17
techniques; in these studies, a 6-month very low calorie diet (900 kcal/day) weight loss
18
program (–20 kg, on average) decreased epicardial fat thickness (from 12.3 mm to 8.3
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1
page 22
mm) in severely obese subjects with body mass index (BMI) of 45 kg/m2 (20), and a
2
weight loss program (–40 kg, on average) after bariatric surgery in severely obese
3
patients with a BMI of 54 kg/m2 contributed to a decrease in the epicardial adipose
4
tissue, suggesting that weight loss alone affects the reduction in epicardial fat thickness
5
(49). Although the current study provides a novel perception, i.e., decreased epicardial
6
fat thickness in response to exercise training in obese men, it has some limitations. First,
7
we did not have a control group. As described earlier, weight loss alone reduces the
8
epicardial fat thickness. Therefore, study on the direct comparison of effects of exercise
9
training with and/or without weight loss on epicardial fat tissue is required for further
10
clarification. However, for precise assessment of validity, the laboratory investigators in
11
the present study were blinded to the baseline and follow-up (at the end of the study)
12
recordings in order to minimize the investigator bias. Second, the relatively small size
13
of our population sample might be concomitant with a type Ⅱ error. Taken together,
14
further studies on the effects of exercise training with and/or without weight loss
15
involving a large number of subjects are required to demonstrate the effectiveness of
16
exercise.
17
Along with clinical interest in epicardial adipose tissue (6–7, 9, 16–20), to date,
18
many studies have focused on epicardial fat tissue by measuring the length of the right
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1
page 23
ventricular epicardial fat using echocardiography (2, 7, 18). Echocardiography cannot
2
be used for the quantification of epicardial fat tissue because of its linear analysis that
3
may not reflect the volumetric quantification of epicardial fat (20). However,
4
multidetector CT provides epicardial fat distribution across the various cardiac segments
5
(1). Moreover, the assessment of epicardial fat volume summation of slices derived
6
from three-dimensional MRI (9) yields the values of volumetric epicardial fat. More
7
recently, cardiac multislice CT scans provide specific values for quantifying the
8
epicardial fat volume (11). Therefore, further study will be required to assess
9
quantitative changes in the adipose tissue surrounding the heart after any intervention
10
program and exercise training.
11
The current study demonstrated that exercise training without diet restriction
12
causes a significant reduction in the epicardial fat thickness along with a decrease in
13
visceral fat, indicating an improvement in obesity-associated cardiovascular and
14
metabolic abnormalities; it also suggests important health benefits of exercise training
15
and reinforces the notion that exercise training is a useful treatment strategy for obesity
16
reduction.
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1
page 24
Acknowledgments
2
We are very grateful to Dr. Yasuhiro Nomata, Takayuki Endo, and Tetsuya Akiba for
3
their outstanding work with the recruitment of subjects and scheduling of the sessions
4
and Yusuke Kato and Yuzou Koyama for assistance during data collection. We also
5
thank the nursing and dietary staff and the subjects for their enthusiastic participation
6
during the intervention period.
7
8
Grant
9
This research was supported by a Grant-in-Aid for Scientific Research (#20650112)
10
from the Japan Ministry of Education, Culture, Sports, Science and Technology.
11
12
Disclosure statement
13
The authors declared no conflict of interest.
14
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page 25
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1
FIGURE LEGENDS
2
Figure 1—Changes in the epicardial fat thickness
3
Epicardial fat thickness measured before and after the 12-week exercise
4
training program. The graph shown indicates the mean ± SD and is representative of the
5
24 subjects.
7
Figure 2—Percent changes in the subcutaneous, visceral, and epicardial fat tissue
8
Percent changes in the subcutaneous, visceral, and epicardial fat tissue
9
measured before and after the 12-wk exercise training intervention. The graph shown
10
indicates the mean ± SE and is representative of the 24 subjects. The * values indicate
11
that the percent changes in the subcutaneous, visceral, and epicardial fat thickness was
12
significantly lower compared with each initial value.
13
14
Figure 3—Correlation between the percentage changes in visceral fat tissue and
15
epicardial fat thickness
16
Scatter plots depicting the relationship between the percentage changes in
17
visceral fat and epicardial fat tissue after the 12-week exercise training program in 24
18
subjects
19
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6
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1
TABLE LEGENDS
2
Table 1—Body composition, aerobic fitness, dietary record, and exercise volume
Anthropometric and dietary variables before and after the exercise training
3
4
program (n = 24). The data are expressed as the mean ± SD.
5
Table 2— Blood parameters before and after the exercise training program
The data are expressed as the mean ± SD; *Paired t test for statistical
7
€
, which was evaluated using a χ2 test. AST, alanine
8
differences except for
9
aminotransferase; AST, aspartate aminotransferase; γ-GTP, γ-glutamyl transpeptidase;
€
10
QUICKI, quantitative insulin sensitivity check index.
Metabolic syndrome was
11
assessed according to the criteria established by the Japan Society for the Study of
12
Obesity.
13
14
Table 3—Stepwise multiple linear regression analysis of obese subjects before and after
15
the exercise training program
16
The stepwise multiple regression analysis using the change in epicardial fat
17
thickness, Δ EpiFat, as the dependent variable was performed to analyze the significant
18
predictors. ΔBMI, ΔVFA, ΔSBP, Δ QUICKI, ΔrestHR, ΔTG/HDL, Δapolipoprotein A-Ι,
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6
page 36
1
Δapolipoprotein A-Ⅱ, and Δ%fat, were used as independent variables. BMI, body mass
2
index; VFA, visceral fat adipose; SBP, systolic blood pressure; QUICKI, quantitative
3
insulin sensitivity check index
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Table 1. Anthropometric and dietary variables before and after the exercise training program
Variable
Pretraining
Posttraining
% Change
P
49.4 ± 9.6
Body mass (kg)
87.7 ± 11.2
84.1 ± 10.2
-4.2 ± 3.0
<.001
30.7± 3.3
29.3 ± 2.9
-4.3 ± 3.0
<.001
Waist (cm)
103.0 ± 7.8
98.4 ± 6.9
-4.4 ± 2.6
<.001
Fat (%)
33.3 ± 3.8
31.0 ± 4.5
-6.8 ± 5.7
<.001
Fat mass (kg)
26.7 ± 4.6
24.0 ± 6.0
-7.9 ± 18.9
.016
Body fat-free mass (kg)
60.6 ± 8.3
59.5 ± 5.5
-1.5 ± 8.7
.290
Systolic blood pressure (mm Hg)
142.8 ± 20.0
139.2 ± 16.4
-2.2 ± 5.0
.028
Diastolic blood pressure (mm Hg)
95.4 ± 14.0
92.5 ± 13.0
-2.8 ± 7.5
.062
VO2peak (ml/kg/min)
28.4 ± 7.2
34.3 ± 5.6
20.5 ± 12.2
<.001
Anaerobic threshold (ml/kg/min)
17.7± 3.9
19.3 ± 4.4
9.4 ± 13.4
.002
Peak heart rate (beats/min)
156 ± 14
157 ± 13
0.8 ± 5.3
.538
Resting heart rate (beats/min)
70 ± 13
65 ± 8
-6.1 ± 8.1
.005
283 ±124
494 ± 126
70.8 ± 54.1
<.001
Pedometer (step/day)
7650 ± 2598
10570 ± 2086
48.7 ± 38.3
<.001
Energy intake (kcal/day)
2196 ± 412
2096 ± 305
-2.3 ± 18.0
.205
Carbohydrate (g/day)
291 ± 75
275 ± 56
-3.1 ± 17.0
.126
Fat (g/day)
62 ± 19
62 ± 14
-0.1 ± 19
.973
Protein (g/day)
85 ± 20
84 ± 20
0.4 ±18
.735
Body Mass Index (kg/m2)
Physical activity (kcal/day)
The graph shown indicates the mean ± SD and is representative of the 24 subjects.
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Age (yr)
Table 2. Blood parameters before and after the exercise training program
Variable
Posttraining
% Change
P
TC (mg/dl)
234.2 ± 39.9
208.8 ± 44.2
-11.2 ± 6.8
<.001
HDLC (mg/dl)
51.7 ± 12.7
52.7 ± 13.2
15.7 ± 12.0
.280
TG (mg/dl)
193.1 ± 118.0
126.0 ± 55.1
-26.0 ± 27.2
.001
LDLC (mg/dl)
143.9 ± 40.4
130.9 ± 40.1
-8.6 ± 12.5
.001
TC/HDLC ratio
4.77 ± 1.33
4.10 ± 1.06
-12.8 ± 8.7
<.001
TG/HDLC ratio
4.44 ± 4.11
2.69 ± 1.74
-26.3 ± 30.6
.005
Apolipoprotein AΙ (mg/dl)
142.3 ± 22.6
129.6 ± 21.8
-8.7 ± 6.7
<.001
Apolipoprotein AΙΙ (mg/dl)
32.6 ± 4.9
28.5 ± 3.8
-12.2 ± 8.6
<.001
AST (IU/L)
33.3 ± 13.0
27.8 ± 9.0
-11.7 ± 25.4
.013
ALT (IU/L)
51.7 ± 32.0
36.9 ± 19.3
-19.3 ± 38.6
.006
γ-GTP (IU/L)
60.8 ± 39.0
47.7 ± 33.5
-15.8 ± 41.2
<.001
Free fatty acids (mEq/L)
0.54 ± 0.16
0.57 ± 0.21
11.3 ± 41.6
.671
Fasting glucose (mg/dl)
103.7 ± 23.4
98.4 ± 11.3
-3.4 ± 9.8
.098
Fasting insulin (µU/ml)
7.94 ± 3.58
6.86 ± 3.42
-1.0 ± 30.3
.041
Insulin sensitivity (QUICKI)
0.35 ± 0.03
0.36 ± 0.03
3.70 ± 7.05
.020
Log High-sensitivity CRP (mg/L)
3.04± 0.47
2.87 ± 0.39
-4.65 ± 4.44
.054
57.7
42.3
-26.7
.033
Metabolic syndrome (%) €
The data are expressed as the mean ± SD; *Paired t test for statistical differences except for €, which was evaluated
using a χ2 test. AST, alanine aminotransferase; AST, aspartate aminotransferase; γ-GTP, γ-glutamyl transpeptidase;
QUICKI, quantitative insulin sensitivity check index. €Metabolic syndrome was assessed according to the criteria
established by the Japan Society for the Study of Obesity.
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Pretraining
Table 3. Stepwise multiple linear regression analysis of obese subjects before and after the exercise
training program
Dependent
variable
∆ Epifat
Independent
variables
βSE
Standardized
β
P-values
Model
r2
∆ VAT
0.101
0.002
0.524
0.000
0.744
∆ SBP
-0.050
0.010
-0.579
0.000
-12.284
3.004
-0.468
0.001
∆ QUICKI
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, ∆VFA, ∆SBP, ∆ QUICKI, ∆restHR, ∆TG/HDL,
∆apolipoprotein A-Ι, ∆apolipoprotein A-ΙΙ, and ∆%fat, were used as independent variables. BMI, body mass index; VAT,
visceral adipose tissue; SBP, systolic blood pressure; QUICKI, quantitative insulin sensitivity check index
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β
8
6
5
4
3
2
1
0
Pretraining
Posttraining
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7
Epicardial fat thickness (mm)
Figure 1.
p < 0.001
10
9
Figure 2.
*
Subcutaneous Fat
Visceral Fat
*
Epicardial Fat
*
-5
-10
-15
-20
P = 0.05
P < 0.05
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% Differences in Fat
0
Figure 3.
-20
r = 0.525
P < 0.01
-10
0
10
20
40
20
0
-20
Change in visceral fat (%)
-40
-60
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Change in epicardial fat (%)
-30