Content uploaded by Tongjian You
Author content
All content in this area was uploaded by Tongjian You on May 19, 2016
Content may be subject to copyright.
ORIGINAL ARTICLE
Addition of aerobic exercise to dietary weight loss
preferentially reduces abdominal adipocyte size
TYou
1
, KM Murphy
1
, MF Lyles
1
, JL Demons
1
, L Lenchik
2
and BJ Nicklas
1,3
1
J Paul Sticht Center on Aging, Section on Gerontology and Geriatric Medicine, Department of Internal Medicine, Winston-
Salem, NC, USA;
2
Department of Radiology, Wake Forest University School of Medicine, Winston-Salem, Winston-Salem,
NC, USA and
3
Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, NC, USA
Objective: To determine if hypocaloric diet, diet plus low-intensity exercise, and diet plus high-intensity exercise differentially
influence subcutaneous abdominal and gluteal adipocyte size in obese individuals.
Design: Longitudinal intervention study of hypocaloric diet, diet plus low-intensity exercise, and diet plus high-intensity exercise
(calorie deficit ¼ 2800 kcal/week, 20 weeks).
Subjects: Forty-five obese, middle-aged women (BMI ¼ 33.070.6 kg/m
2
, age ¼ 5871 years).
Measurements: Body composition testing and adipose tissue biopsies were conducted before and after the interventions.
Subcutaneous abdominal and gluteal adipocyte size was determined.
Results: All three interventions reduced body weight, fat mass, percent fat, and waist and hip girths to a similar degree. Diet
only did not change subcutaneous abdominal adipocyte size, whereas both diet plus exercise groups significantly reduced
abdominal adipocyte size. Changes in abdominal adipocyte size in the diet plus exercise groups were significantly different from
that of the diet group. Gluteal adipocyte size decreased similarly in all three groups.
Conclusion: Addition of exercise training to dietary weight loss preferentially reduces subcutaneous abdominal adipocyte size in
obese women. This may be of importance for the treatment of health complications associated with subcutaneous abdominal
adiposity.
International Journal of Obesity (2006) 30, 1211–1216. doi:10.1038/sj.ijo.0803245; published online 31 January 2006
Keywords: exercise training; hypocaloric diet; abdominal fat; gluteal fat; fat cell size
Introduction
Obesity is a risk factor for type 2 diabetes and cardiovascular
disease.
1–2
However, not all obese people develop these
diseases and some may have normal glucose tolerance and
lipid profile.
3
Location of body fat is one risk factor that
differentiates obese persons with and without metabolic
complications,
3,4
and obese people with more upper-body
(abdominal) fat are under a higher metabolic risk than those
with more lower-body (gluteal-femoral) fat.
5–7
In fact,
abdominal obesity, including subcutaneous and visceral
fatness, is an accepted component of the clustering of
metabolic risk factors known as the metabolic syndrome.
8
In addition to total and abdominal obesity, adipose
cellularity is another potential factor that contributes to
elevated metabolic risk. For example, obese women with
larger subcutaneous abdominal adipocytes are more likely to
have hyperinsulinemia and glucose intolerance.
5,9,10
More-
over, subcutaneous abdominal adipocyte size predicts type 2
diabetes, independent of obesity and insulin resistance.
11
Interestingly, subcutaneous gluteal adipocyte size may be
more sensitive for predicting metabolic syndrome in African-
American than Caucasian older women.
12
Life style modifications, such as dietary weight loss and
increasing physical activity are advocated for the treatment
of total and central obesity and prevention of diabetes and
cardiovascular disease.
8,13
Although both diet and exercise
interventions reduce total body fat mass, exercise may be
more efficient in decreasing abdominal adiposity.
14–19
Results from observational studies indicate that abdominal
adiposity is inversely related to aerobic fitness
14
and physical
activity.
15
Interventional studies show that exercise-induced
weight loss preferentially reduces abdominal fat.
16–19
Although one study did not show an effect of exercise
Received 30 August 2005; revised 14 October 2005; accepted 29 October
2005; published online 31 January 2006
Correspondence: Dr T You, J Paul Sticht Center on Aging, G Floor, Wake Forest
University School of Medicine, Medical Center Boulevard, Winston-Salem, NC
27157.
E-mail: tyou@wfubmc.edu
International Journal of Obesity (2006) 30, 1211–1216
&
2006 Nature Publishing Group All rights reserved 0307-0565/06
$
30.00
www.nature.com/ijo
intensity on changes in body composition and fat distri-
bution in response to exercise training alone,
20
it is not
known if exercise intensity is a factor to influence abdominal
fat distribution during dietary weight loss.
It has been reported that the fat-reducing effect of both
diet and exercise is through a decrease in fat cell size.
21,22
As
elevated metabolic risk is highly linked with adipocyte size,
especially in the abdominal region,
5,9–11
identification of the
most effective treatment to reduce abdominal adipocyte size
is of clinical significance. Thus, we tested the hypothesis that
dietary weight loss combined with high-intensity aerobic
exercise training would be more effective in selectively
reducing abdominal adipocyte size, compared to weight loss
with low-intensity exercise training or weight loss alone in
obese older women.
Methods
Subjects
All women were recruited from the Piedmont Triad area of
North Carolina, and enrolled in the study based on the
following inclusion/exclusion criteria: (1) overweight or
obese (BMI ¼ 25–40 kg/m
2
and waist girth 488 cm), (2) older
(age ¼ 50–70 years, and at least 1 year without menses), (3)
nonsmoking, (4) not on hormone replacement therapy, (5)
sedentary (o15 min of exercise, two times/week) in the past
6 months, and (6) weight-stable (o5% weight change) for at
least 6 months before enrollment. All women provided
informed consent to participate in the study according to the
guidelines of the Wake Forest University Institutional Review
Board for Human Research.
Initial screening included a medical history review,
physical examination, fasting blood profile (lipoprotein
lipids and glucose) and 12-lead resting electrocardiogram.
Participants with evidence of untreated hypertension (blood
pressure 4160/90 mmHg), hypertriglyceridemia (triglycer-
ides 4400 mg/dl), insulin-dependent diabetes, active cancer,
liver, renal or hematological disease, or other medical
disorders were excluded. On a second screening visit, the
subjects underwent a graded exercise test to exclude those
with an abnormal cardiovascular response to exercise.
23
Forty-nine women were enrolled in the study and randomly
assigned to either a hypocaloric diet only (Diet), a diet plus
low-intensity exercise (Diet þ LE), or a diet plus high-
intensity exercise (Diet þ HE) intervention for a period of
20 weeks.
Study design
Baseline measurements of body composition, body fat
distribution, maximal aerobic capacity (VO
2
max) and adi-
pocyte sizes were performed after at least 2 weeks of weight
stability before the interventions. Subjects reported to the
facility on the first day for the measurement of body
composition, body fat distribution and VO
2
max. The sub-
jects were asked to remain sedentary and the fat biopsies
were performed at least 5 days after the VO
2
max test. The fat
biopsies took place at the same time of morning (0700–0900
hours) after an overnight fast. After the 20-week interven-
tions, the women were retested at their lower body weight in
the same manner as at baseline. The diet plus exercise groups
continued to exercise during this testing period, but the
postintervention fat biopsies occurred at least 36 h after an
exercise session.
Study interventions
During the 20-week interventions, all women were provided
food for their lunch and supper, which was prepared by the
Wake Forest University General Clinical Research Center
(GCRC) metabolic kitchen staff. These meals were prepared
individually after women chose from a hypocaloric menu
designed by a registered dietitian (RD). Women purchased
and prepared their breakfast meal, in consultation with the
GCRC dietitian, from this same menu. They were allowed 2
free days per month, during which they were given guide-
lines for diet intake and asked to report all intake. They were
also allowed to consume as many noncaloric, noncaffeinated
beverages as they liked. In addition, all women were
provided with a daily calcium supplement (1000 mg/day).
The diet only group was asked not to alter their physical
activity habits during the study. Both diet plus exercise
groups walked on a treadmill 3 days/week at a target
heart rate calculated from the Karvonen equation
((HRR (intensity) þ resting heart rate),
24
where heart rate
reserve (HRR) is maximal heart rate minus resting heart rate
obtained from each subject’s VO
2
max test. The duration and
intensity of the exercise progressed from 15 to 20 min at
45–50% of HRR during the first week to 55 min at 45–50%
HRR for the low-intensity group, and 30 min at 70–75% HRR
for the high-intensity group by the second month. The
calorie deficits of all women were adjusted to B2800 kcal/
week. The deficits for the diet only group resulted totally
from reduction in dietary intake, whereas deficits for the diet
plus exerciser groups resulted from both reductions in
dietary intake (B2400 kcal/week) and in exercise expendi-
ture (B400 kcal/week). The average daily calorie intake
recorded by all women was 99.470.3% of the provided
calorie level. The exercise compliance was 92.371.7% for the
low-intensity exercise group, and 87.972.3% for the high-
intensity exercise group.
Body composition
Height and weight were measured to calculate BMI (kg/m
2
).
Waist (minimal circumference) and hip (maximal circum-
ference) was measured and waist-to-hip ratio was calculated.
Fat mass, lean mass and percent body fat were measured by
dual energy X-ray absorptiometry (Hologic Delphi QDR,
Bedford, MA, USA).
Exercise, weight loss and adipocyte size
T You et al
1212
International Journal of Obesity
Maximal aerobic capacity
VO
2
max was measured on a motor-driven treadmill (Medical
Graphics Corporation, Minneapolis, MN, USA) during a
progressive exercise test to voluntary exhaustion. A ramp
treadmill protocol was used for the exercise test. The speed of
the treadmill was set at a constant rate according to
individual ability, and the incline increased at small intervals
continuously throughout the test. Each test was set for a
duration of 12 min with a goal of 12 metabolic equivalents,
and the treadmill self-adjusted the incline to reach that goal.
A valid VO
2
max was obtained when a respiratory exchange
ratio (RER) of 1.10 had been reached. If the participant did
not reach a RER of 1.10, the test was repeated.
Adipocyte size
Subcutaneous adipose tissue from both the abdominal and
gluteal regions was taken by aspiration with a 16-gauge
needle under local anesthesia (2% xylocaine) after an
overnight fast. Adipocytes were isolated in a Krebs-Ringer
N-2-hydroxyethylpiperazine-N
00
-2-ethanesulfonic acid buffer
(pH 7.4, KRH) containing 4% bovine serum albumin, 5 m
M
glucose, 0.1 mM ascorbic acid, 200 nM adenosine, and 1 mg/ml
collagenase, and in a shaking water bath at 100 r.p.m., 371C
for 45 min.
25
Isolated cells were filtered through 400-mM
nylon mesh and washed three times with enzyme-free KRH
buffer and resuspended to a final concentration of 20 000–
30 000 cells/ml. An aliquot of the final cell suspension was
placed on a glass slide and diameters of 100 cells per site were
measured using a microscope equipped with a graduated
ocular. The average cell diameter and standard deviation
were calculated and the average cell weight for each site was
determined as described.
26
Statistics
Statistical analyses were performed using SPSS 10.1. for
Windows (Chicago, IL, USA). First, within-group differences
between preintervention and postintervention measures of
all variables were determined using a paired t-test. Differ-
ences among the intervention groups at baseline and over-
time changes in response to the interventions were
determined using one-way ANOVA. The Fisher’s LSD post
hoc test was used to determine any group differences if an
overall group effect was ascertained. All data are presented as
means7standard error, and the level of significance was set
at Po0.05 for all analyses.
Results
Subject characteristics
Forty-five (Diet: n ¼ 15, Diet þ LE: n ¼ 14, Diet þ HE: n ¼ 16)
of the initial 49 women completed the interventions. Four
women dropped out of the program owing to personal
reasons and time constraints. Of the 45 women who
completed the study, three women did not complete the
VO
2
max test. Owing to insufficient adipose tissue yield
obtained from the biopsies, four women did not have
measures of abdominal adipocyte size and seven women
did not have measures of gluteal adipocyte size. There were
no differences in age, years postmenopause, or percent of
African Americans among the three groups.
Effects of diet, diet plus low-intensity exercise, and diet plus
high-intensity exercise on body composition and aerobic fitness
Body composition measures before and after the interven-
tions in the three groups are shown in Table 1. At baseline,
there were no group differences in weight, fat mass, lean
mass or percent body fat. After the 5-month interventions,
all three groups lost a similar amount of body weight
(Diet: 11.370.8%; Diet þ LE: 12.871.4%; Diet þ HE:
10.071.2%), consisting of approximately 70–80% adipose
tissue. Likewise, there were similar reductions in lean mass
and percent body fat in all three groups.
At baseline, there were no group differences in absolute or
relative VO
2
max (Table 1). All three interventions did not
change absolute VO
2
max, but increased relative VO
2
max
(Diet: 8.872.0%; Diet þ LE: 12.672.3%; Diet þ HE: 20.876.6%).
There were no significant group differences among changes
in absolute or relative VO
2
max.
Table 1 Body composition and aerobic fitness in the Diet, Diet+LE, and
Diet+HE groups before and after interventions and over-time changes
Pre Post Change
Weight (kg)
Diet (n ¼ 15) 91.272.2 80.972.0*** 10.470.8
Diet+LE (n ¼ 14) 86.672.3 75.772.8*** 10.971.2
Diet+HE (n ¼ 16) 85.873.8 77.073.2*** 8.871.2
Fat mass (kg)
Diet (n ¼ 15) 39.971.7 32.871.7*** 7.070.8
Diet+LE (n ¼ 14) 37.771.3 29.771.6*** 8.070.9
Diet+HE (n ¼ 16) 38.272.1 31.271.9*** 7.070.7
Lean mass (kg)
Diet (n ¼ 15) 51.470.9 47.370.9*** 4.170.5
Diet+LE (n ¼ 14) 49.371.5 45.871.5*** 3.570.4
Diet+HE (n ¼ 16) 48.671.5 45.671.4*** 3.070.4
Percent body fat (%)
Diet (n ¼ 15) 42.471.1 40.071.2*** 2.870.6
Diet+LE (n ¼ 14) 42.270.8 38.071.1*** 4.270.7
Diet+HE (n ¼ 16) 42.670.8 39.171.0*** 3.570.4
Absolute VO
2
max (l/min)
Diet (n ¼ 14) 1.7670.07 1.7270.07 0.0470.07
Diet+LE (n ¼ 13) 1.8370.07 1.7870.05 0.0570.04
Diet+HE (n ¼ 15) 1.6770.09 1.6870.08 0.0170.04
Relative VO
2
max (ml/min/kg)
Diet (n ¼ 14) 19.970.8 21.670.9** 1.770.4
Diet+LE (n ¼ 13) 20.870.8 23.270.6*** 2.470.4
Diet+HE (n ¼ 15) 19.271.0 22.470.7** 3.370.9
All data are means7s.e. **Po0.01, ***Po0.001 compared with baseline.
Exercise, weight loss and adipocyte size
T You et al
1213
International Journal of Obesity
Effects of diet, diet plus low-intensity exercise, and diet plus
high-intensity exercise on body fat distribution and regional
adipocyte size
At baseline, there were no group differences in waist girth,
hip girth, or waist-to-hip ratio (Table 2). The interventions
reduced waist and hip girths to a similar degree in all three
groups, but did not significantly change waist-to-hip ratio in
any group.
There were no group differences in abdominal or gluteal
adipocyte size at baseline (Table 2). Diet alone did not
decrease abdominal adipocyte size; however, diet plus low-
intensity exercise and diet plus high-intensity exercise
significantly reduced abdominal adipocyte size. Changes in
abdominal adipocyte size in the two exercise groups
(Diet þ LE: -18.473.9%; Diet þ HE: 16.873.5%) were sig-
nificantly different from that of the diet only group
(0.876.2%). Gluteal adipocyte size decreased similarly in
all three groups (Diet: 12.475.3%; Diet þ LE: 13.874.5%;
Diet þ HE: 19.874.4%) (Figure 1). Diet only increased
abdominal-to-gluteal adipocyte size ratio (14.273.8%). Diet
plus low-intensity exercise and diet plus high-intensity
exercise did not change adipocyte size ratio. There were no
group differences among changes in adipocyte size ratio.
Discussion
This study investigated whether dietary weight loss plus
high-intensity aerobic exercise training would be more
effective in reducing abdominal adipocyte size, compared
to weight loss plus low-intensity exercise training or weight
loss alone in obese older women. The findings showed that
addition of either high-intensity or low-intensity aerobic
exercise training to dietary weight loss significantly reduced
subcutaneous abdominal, but not gluteal, adipocyte size.
However, diet plus high-intensity exercise and diet plus low-
intensity exercise did not differ in their effects on abdominal
adipocyte size.
Our results showed that weight loss alone decreased both
waist and hip girths; however, there were no changes in
waist-to-hip ratio. These results were similar to our earlier
findings in overweight and obese women,
27,28
but different
from findings of another study showing that 4 weeks of very-
low-calorie-diet (VLCD) treatment decreased waist-to-hip
ratio in android obese women.
29
The possible reason for
the different findings might be the different subject
characteristics, diet types and intervention terms. In obese
men, 4 months of exercise training reduced body weight, fat
mass, and waist-to-hip ratio, but did not change fat-free
mass, indicating that exercise training could preferentially
reduce abdominal fat and maintain muscle mass.
19
However,
another study investigated effects of exercise amount/
intensity on body fatness and found exercise amount
affected the degree of weight loss and fat mass loss, but
neither exercise amount nor intensity influenced regional fat
distribution.
20
Hypocaloric diet and exercise training can reduce body fat
through a decrease in fat cell size, but not cell number.
21,22
Although both diet and exercise treatments reduce total
body fatness, it has been suggested that exercise training
preferentially reduces abdominal adiposity.
14–19
The current
study further demonstrates that addition of aerobic exercise
Table 2 Body fat distribution and regional adipocyte size in the Diet,
Diet+LE, and Diet+HE groups before and after interventions and over-time
changes
Pre Post Change
Waist girth (cm)
Diet (n ¼ 15) 100.972.0 92.172.1*** 8.871.0
Diet+LE (n ¼ 14) 100.272.2 90.772.8*** 9.471.3
Diet+HE (n ¼ 16) 96.472.5 87.172.2*** 9.371.4
Hip girth (cm)
Diet (n ¼ 15) 118.872.2 111.572.2*** 7.371.3
Diet+LE (n ¼ 14) 116.772.2 107.172.2*** 9.771.4
Diet+HE (n ¼ 16) 116.672.4 108.472.4*** 8.270.8
Waist-to-hip ratio
Diet (n ¼ 15) 0.8570.02 0.8370.02 0.0270.01
Diet+LE (n ¼ 14) 0.8670.02 0.8570.02 0.0170.02
Diet+HE (n ¼ 16) 0.8370.02 0.8070.01 0.0270.01
Abdominal adipocyte size (mg)
Diet (n ¼ 12) 0.8370.06 0.8070.04 0.0470.04
Diet+LE (n ¼ 14) 0.8270.03 0.6670.03*** 0.1670.04
w
Diet+HE (n ¼ 15) 0.8970.04 0.7370.04*** 0.1670.04
w
Gluteal adipocyte size (mg)
Diet (n ¼ 12) 0.9670.07 0.8170.03* 0.1570.05
Diet+LE (n ¼ 11) 0.8870.04 0.7570.05* 0.1370.04
Diet+HE (n ¼ 15) 0.9570.03 0.7770.05*** 0.1970.04
Abdominal-to-gluteal size ratio
Diet (n ¼ 12) 0.8870.05 0.9970.04** 0.1170.03
Diet+LE (n ¼ 11) 0.9370.06 0.9070.02 0.0370.06
Diet+HE (n ¼ 15) 0.9470.04 0.9870.04 0.0470.06
All data are means7s.e. *Po 0.05, **Po0.01, ***Po0.001 compared with
baseline.
w
Po0.05 compared with diet only.
−30
−25
−20
−15
−10
−5
0
Abdominal Gluteal
Diet
Diet+LE
Diet+HE
Change in adipocyte size (%)
R
R
Figure 1 Percent changes in regional adipocyte size in all three intervention
groups.
w
Po0.05 compared with diet only.
Exercise, weight loss and adipocyte size
T You et al
1214
International Journal of Obesity
training to dietary weight loss results in a larger decrease in
abdominal, but not gluteal, adipocyte size. These results
support those of an earlier observational study that endur-
ance-trained premenopausal women had lower abdominal,
but not femoral, adipocyte size than sedentary premeno-
pausal women.
30
Moreover, our results indicate that both
high-intensity and low-intensity exercise training are bene-
ficial to at-risk obese women undergoing dietary weight loss.
Weight loss through the current approach may not evenly
influence adipocyte size in different regions. This is
supported by our findings that diet alone increased abdom-
inal-to-gluteal adipocyte size ratio. This may be due to
regional differences in metabolic adaptations of adipocytes
to the hypocaloric diet, including a greater reduction in
hormone-sensitive lipase (HSL, enzyme for triglyceride
hydrolysis) activity and increase in lipoprotein lipase (LPL,
enzyme for triglyceride accumulation) activity in abdominal,
compared to gluteal adipocytes. In addition, regional
difference in estrogen receptor activity may be a possible
mechanism to influence lipolysis and adipocyte size.
30
More
studies are needed to investigate the mechanism underlying
the unparallel changes in the regional adipocyte sizes of the
abdominally obese women in response to hypocaloric diet.
Similarly, changes in regional adipoctyte size in response to
exercise training were likely through modulations on lipid
metabolism. As previously described,
31
endurance-trained
women have lower subcutaneous abdominal adipocyte size
than sedentary women, which may be due to a preferential
lipid mobilization from subcutaneous abdominal, compared
to femoral, adipose tissue in endurance-trained women.
These changes may involve both the HSL and LPL pathways.
Moreover, it is not known if exercise training could
differentially influence estrogen receptor activity in these
fat regions.
We previously conducted two intervention studies to
measure abdominal and gluteal adipocyte size in obese
postmenopausal women.
27,28
Although one study
27
showed
both hypocaloric diet alone and diet plus exercise training
reduced abdominal and gluteal adipocyte size, the other
study
28
found diet plus exercise, but not diet alone,
decreased abdominal and gluteal adipocyte size. In both
studies, intervention-induced adipocyte size changes were
similar between abdominal and gluteal regions. There are
two possible reasons for the different findings between the
current study and the two previous studies. First, although
subjects in the earlier studies were also overweight or obese
postmenopausal women, some of them did not have
abdominal obesity. In the current study, all subjects were
abdominally obese (waist girth 488 cm) postmenopausal
women. Enlarged subcutaneous abdominal adipocytes may
be more resistant to dietary treatment in women with more
severely abdominal obesity. Second, the two earlier studies
used a behavioral approach for dietary weight loss. The
current study provided food to the subjects through the
metabolic kitchen, which resulted in better compliances in
caloric intake and greater amounts of weight loss compared
to the earlier studies. Variation in diet compliance and
amount of weight loss may influence findings of these
studies.
It is notable that changes in waist and hip girths do not
exactly reflect changes in subcutaneous gluteal and abdom-
inal adipocyte sizes in response to diet and exercise. This can
be explained by the influence of visceral fat, intramuscular
fat and fat-free mass. In addition, sample sizes among these
intervention groups are relatively small, which might
influence the statistical power of data analysis. Larger studies
need to be conducted to confirm our findings. Moreover,
adipocyte metabolic properties were not tested in this study,
although such data would help clarify the mechanisms for
changes in regional adipocyte size in response to diet and
exercise.
In summary, addition of either high-intensity or low-
intensity aerobic exercise training to dietary weight loss
preferentially reduces subcutaneous abdominal adipocyte
size, whereas dietary weight loss with or without exercise
similarly reduces gluteal adipocyte size in abdominally obese
women. These findings are consistent with other research
showing that exercise training selectively decreases abdom-
inal fat. Considering the health problems associated with
enlarged subcutaneous abdominal adipocytes, addition of
exercise to dietary weight loss may be important for the
treatment of these complications. Future studies need to
focus on the link between metabolic biomarkers and regional
adipocyte size in response to diet and exercise training.
Acknowledgements
We are grateful to the study coordinators, dietitians, exercise
physiologists, nurses, and laboratory technicians of the
Section of Gerontology and Geriatric Medicine, and the
General Clinical Research Center at Wake Forest University
School of Medicine for their assistance in the conduct of this
study. We also thank all women who voluntarily participated
in this study. This study was supported by NIH Grant R01-
AG/DK20583, Wake Forest University Claude D. Pepper
Older Americans Independence Center (P30-AG21332), and
Wake Forest University General Clinical Research Center
(M01-RR07122).
References
1 Manson JE, Colditz GA, Stampfer MJ, Willett WC, Rosner B,
Monson RR et al. A prospective study of obesity and risk
of coronary heart disease in women. N Engl J Med 1990; 322:
882–889.
2 Colditz GA, Willett WC, Stampfer MJ, Manson JE, Hennekens
CH, Arky RA et al. Weight as a risk factor for clinical diabetes in
women. Am J Epidemiol 1990; 132: 501–513.
3 Brochu M, Tchernof A, Dionne IJ, Sites CK, Eltabbakh GH, Sims
EA et al. What are the physical characteristics associated with a
normal metabolic profile despite a high level of obesity in
Exercise, weight loss and adipocyte size
T You et al
1215
International Journal of Obesity
postmenopausal women? J Clin Endocrinol Metab 2001; 86:
1020–1025.
4 You T, Ryan AS, Nicklas BJ. The metabolic syndrome in obese
postmenopausal women: relationship to body composition,
visceral fat, and inflammation. J Clin Endocrinol Metab 2004; 89:
5517–5522.
5 Kissebah AH, Vydelingum N, Murray R, Evans DJ, Hartz AJ,
Kalkhoff RK et al. Relation of body fat distribution to metabolic
complications of obesity. J Clin Endocrinol Metab 1982; 54:
254–260.
6 Bjorntorp P. ‘Portal’ adipose tissue as a generator of risk factors
for cardiovascular disease and diabetes. Arteriosclerosis 1990; 10:
493–496.
7 Folsom AR, Kushi LH, Anderson KE, Mink PJ, Olson JE, Hong CP
et al. Associations of general and abdominal obesity with multiple
health outcomes in older women: the Iowa Women’s Health
Study. Arch Intern Med 2000; 160: 2117–2128.
8 Expert Panel on Detection, Evaluation, and Treatment of High
Blood Cholesterol in Adults. Executive Summary of The Third
Report of The National Cholesterol Education Program (NCEP)
Expert Panel on Detection, Evaluation, and Treatment of High
Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA
2001; 285: 2486–2497.
9 Bjorntorp P, Bengtsson C, Blohme G, Jonsson A, Sjostrom L,
Tibblin E et al. Adipose tissue fat cell size and number in relation
to metabolism in randomly selected middle-aged men and
women. Metabolism 1971; 20: 927–935.
10 Bjorntorp P, Gustafson A, Persson B. Adipose tissue fat cell size
and number in relation to metabolism in endogenous hyper-
triglyceridemia. Acta Med Scand 1971; 190: 363–367.
11 Weyer C, Foley JE, Bogardus C, Tataranni PA, Pratley RE. Enlarged
subcutaneous abdominal adipocyte size, but not obesity itself,
predicts type II diabetes independent of insulin resistance.
Diabetologia 2000; 43: 1498–1506.
12 Tittelbach TJ, Berman DM, Nicklas BJ, Ryan AS, Goldberg AP.
Racial differences in adipocyte size and relationship to
the metabolic syndrome in obese women. Obes Res 2004; 12:
990–998.
13 Physical activity and cardiovascular health. NIH consensus
development panel on physical activity and cardiovascular
health. JAMA 1996; 276: 241–246.
14 Wong SL, Katzmarzyk P, Nichaman MZ, Church TS, Blair SN, Ross
R. Cardiorespiratory fitness is associated with lower abdominal
fat independent of body mass index. Med Sci Sports Exerc 2004; 36:
286–291.
15 Riechman SE, Schoen RE, Weissfeld JL, Thaete FL, Kriska AM.
Association of physical activity and visceral adipose tissue in
older women and men. Obes Res 2002; 10: 1065–1073.
16 Despres JP, Tremblay A, Nadeau A, Bouchard C. Physical training
and changes in regional adipose tissue distribution. Acta Med
Scand Suppl 1988; 723: 205–212.
17 Despres JP, Pouliot MC, Moorjani S, Nadeau A, Tremblay A,
Lupien PJ et al. Loss of abdominal fat and metabolic response
to exercise training in obese women. Am J Physiol 1991; 261:
E159–E167.
18 Schwartz RS, Shuman WP, Larson V, Cain KC, Fellingham GW,
Beard JC et al. The effect of intensive endurance exercise training
on body fat distribution in young and older men. Metabolism
1991; 40: 545–551.
19 Mayo MJ, Grantham JR, Balasekaran G. Exercise-induced weight
loss preferentially reduces abdominal fat. Med Sci Sports Exerc
2003; 35: 207–213.
20 Slentz CA, Duscha BD, Johnson JL, Ketchum K, Aiken LB, Samsa
GP et al. Effects of the amount of exercise on body weight, body
composition, and measures of central obesity: STRRIDEFa
randomized controlled study. Arch Intern Med 2004; 164: 31–39.
21 Bjorntorp P, Carlgren G, Isaksson B, Krotkiewski M, Larsson B,
Sjostrom L. of an energy-reduced dietary regimen in relation to
adipose tissue cellularity in obese women. Am J Clin Nutr 1975;
28: 445–452.
22 Bjorntorp P. Exercise in the treatment of obesity. Clin Endocrinol
Metab 1976; 5: 431–453.
23 ACSM’s guidelines for exercise testing and prescription. 6th edn.
Lippincott Williams & Wilkins, Philadelphia, 2000.
24 Karvonen MJ, Kentala E, Mustala O. The effects of training on
heart rate; a longitudinal study. Ann Med Exp Biol Fenn 1957; 35:
307–315.
25 Rodbell M. Metabolism of isolated fat cells. I. Effects of hormones
on glucose metabolism and Lipolysis. J Biol Chem 1964; 239:
375–380.
26 Hirsch J, Gallian E. Methods for the determination of adipose cell
size in man and animals. J Lipid Res 1968; 9: 110–119.
27 Nicklas BJ, Rogus EM, Goldberg AP. Exercise blunts declines in
lipolysis and fat oxidation after dietary-induced weight loss in
obese older women. Am J Physiol 1997; 273: E149–E155.
28 You T, Berman DM, Ryan AS, Nicklas BJ. Effects of hypocaloric
diet and exercise training on inflammation and adipocyte
lipolysis in obese postmenopausal women. J Clin Endocrinol
Metab 2004; 89: 1739–1746.
29 Hainer V, Stich V, Kunesova M, Parizkova J, Zak A, Wernischova V
et al. Effect of 4-wk treatment of obesity by very-low-calorie diet
on anthropometric, metabolic, and hormonal indexes. Am J Clin
Nutr 1992; 56: 281S–282S.
30 Pedersen SB, Kristensen K, Hermann PA, Katzenellenbogen JA,
Richelsen B. Estrogen controls lipolysis by up-regulating alpha2A-
adrenergic receptors directly in human adipose tissue through
the estrogen receptor alpha. Implications for the female fat
distribution. J Clin Endocrinol Metab 2004; 89: 1869–1878.
31 Mauriege P, Prud’Homme D, Marcotte M, Yoshioka M, Tremblay
A, Despres JP. Regional differences in adipose tissue metabolism
between sedentary and endurance-trained women. Am J Physiol
1997; 273: E497–E506.
Exercise, weight loss and adipocyte size
T You et al
1216
International Journal of Obesity