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Research Article
Open Access
Changes in Serum Adipocytokines and Inflammatory Biomarkers Following
One-Year of Exercise Training in Obese Adolescents
Barbara Garanty-Bogacka1*, Monika Rać3, Małgorzata Syrenicz1, Aneta Gębala1,2, Mieczysław Walczak4 and Anhelli Syrenicz5
1Independent Laboratory of Propaedeutics of Children’s Diseases, Pomeranian Medical University, Szczecin, Poland
2Division of Paediatrics, Gastroenterology and Rheumatology of the Zdroje Clinic in Szczecin, Poland
3Department of Biochemistry and Medical Chemistry Pomeranian Medical University, Szczecin, Poland
4Department of Paediatrics, Endocrinology, Diabetology, Inborn Errors of Metabolism and Cardiology Pomeranian Medical University, Szczecin, Poland
5Department of Endocrinology, Metabolic Diseases and Internal Diseases, Pomeranian Medical University, Szczecin, Poland
*Corresponding author:
Dr. Barbara Garanty-Bogacka
Independent
Laboratory of Propaedeutics of Children’s Diseases Pomeranian Medical
University
Szczecin, Poland E-mail: garbog4@wp.pl
Received July 22, 2012; Accepted August 23, 2012; Published August 28, 2012
Citation: Garanty-Bogacka B, Rac M, Syrenicz M, Gebala A, Walczak M, et al.
(2012) Changes in Serum Adipocytokines and Inflammatory Biomarkers Following
One-Year of Exercise Training in Obese Adolescents. J Diabetes Metab 3:212.
doi:10.4172/2155-6156.1000212
Background: Obese individuals commonly demonstrate elevated levels of serum inflammatory markers and cell
adhesion molecules. The later are known to be implicated in the pathogenesis of cardiovascular disease. Increased
physical activity has been shown to be effective in altering adipocytokines, and inflammatory markers; however, little
is known about the effect of exercise training alone on these parameters in children and adolescents.
Aim: This study was designed to compare the effects of moderate-intensity training and caloric restriction on
serum adipocytokines as well as markers of inflammation and cell adhesion in obese adolescents.
Material and methods: Fifty six obese adolescents, participating in an obesity intervention program, were
studied before and after 1 year program consisting of moderate physical activity (exercise group including 37
participants) or hypocaloric diet (diet group: 19 subjects). Highly sensitive C-reactive protein, interleukin-6, adipocyte
fatty acid-binding protein-4, adiponectin, intracellular cell adhesion molecule-1 and vascular adhesion molecule-1
were measured before and after intervention. Body composition, blood pressure, fasting blood glucose and insulin
were also assessed.
Results: After 1 year, a significant reduction in all adiposity parameters were observed in both groups, but the
changes were more prominent in the exercise group. Physical training was also favourable compared with hypocaloric
diet in reducing serum markers of inflammation (P <0.009 for C-reactive protein; P<0.002 for interleukin-6) and
cell adhesion (P<0.020 for intracellular cell adhesion molecule-1; P<0.000 for vascular adhesion molecule-1). In
addition, exercise training induced a rise of adiponectin (P<0.000) and fall in fatty acid-binding protein-4 (P < 0.000),
independent of weight loss.
Conclusions: We conclude that moderate-intensity training alone reduced blood markers of inflammation
and cell adhesion in obese adolescents more than observed after caloric restriction. Exercise training was also
associated with potentially favourably changes in serum adipocytokines.
Keywords
Exercise; Obesity; Inflammation; Children
Introduction
With an increasing prevalence [1], adolescent obesity often precedes
adulthood obesity and is associated with increased cardiovascular
morbidity and mortality [2], therefore represents a major public health
problem. Since serious co-morbidities are common in obese adults, it is
important to search for early markers or risk factors for cardiovascular
disease (CVD) in obese youth. There is increasing evidence that obesity
is associated with low-level inflammation which may be responsible
for many metabolic complications of obesity [3]. Obese individuals
commonly demonstrate increased levels of blood markers suggesting
low-grade chronic systemic inflammation [4]. At least 24 adipokines
were identified whose serum levels are enhanced in obesity, and most
of them have pro-inflammatory properties [3]. The main inflammatory
molecule is C-reactive protein (CRP) which is actually acute phase
protein primarily secreted by the liver in response to adipokine
interleukin-6 [5], and both molecules are independently associated
with obesity and cardiovascular disease [6]. Interleukin-6 (IL-6) is
an immunomodulatory cytokine which may exert pro- and antiinflammatory
[3], as well as metabolic effects [7]. IL-6 and CRP may
affect endothelial function via either direct or indirect mechanisms such
as reducing production of nitric oxide and stimulating inflammationoxidative
stress pathways [8].
Elevated levels of pro-inflammatory factors also appear to directly
induce expression of cell adhesion molecules in endothelium and
recruit of leukocytes [9], which is essential to the pathogenesis of
atherosclerosis [10]. It has been found that elevated serum levels of
soluble intracellular adhesion molecule-1 (sICAM-1) and soluble
vascular cell adhesion molecule-1 (sVCAM-1) were associated with
increased risk for coronary heart disease [11].
Pro-inflammatory state and endothelial dysfunction have generally
been considered as two major mechanisms contributing to early
stages and to further development of atherosclerosis [8,10]. Many of
the pro-inflammatory and pro-atherogenic factors associated with
obesity-related vascular disease in adults have also been described in children [12-14]. These included decreased adiponectin (ADN) level
and increased adipocyte fatty acid-binding protein (FABP-4) level
in the serum. Circulating level of adiponectin, cytokine released by
adipose tissue, has been reported to be lower in human obesity and
the reduction is associated with the development of obesity-related
metabolic syndrome, including type 2 diabetes and atherosclerosis [15].
Adiponectin promote the production of NO in endothelial cells, and
hypoadiponectinemia is associated with impaired endothelial function
[16].
Compared to adult studies, the markers mentioned above were
assessed in children with the exception of adipocyte fatty acid-binding
protein. Adipocyte FABP is a major cytoplasmic protein in adipocytes
and macrophages and is involved in the intracellular regulation of lipid
metabolism, but may be also released into the bloodstream [17]. Results
of many studies suggest that FABP is closely associated with insulin
resistance, type 2 diabetes and atherosclerosis [17-19].
Numerous studies in obese patients have shown that even moderate
weight loss through dietary changes and physical exercises is effective
in preventing and managing obesity-associated disorders [20,21]. It
has been postulated that aerobic exercise training reduce the risk of
CVD both independently and through modification of traditional risk
factors, such as hypertension, dyslipidemia, insulin resistance and type
2 diabetes [22].
It is generally accepted that the effectiveness of obesity treatment in
pediatric population is unsatisfactory, especially in older children and
adolescents. Only few therapeutic interventions involving adolescents
have produced significant long-term weight loss [23]. As obesityassociated
factors still predominate over genetic predisposition in the
pathogenesis of obesity-related disorders, treatment strategies in obese
children are based on changes in lifestyle, including increased physical
activity and/or dietary modifications [24]. On the other hand, diet
restriction and daily physical activities at the same time throughout a
long period of time are not accepted by teenagers, and most of them
drop-out from an obesity intervention program or choose only one
method.
Therefore, the following study was performed to compare the effects
of moderate-intensity physical training and hypocaloric diet on serum
levels of selected adipocytokines as well as markers of inflammation
and cell adhesion in obese adolescents.
Patients and Methods
The study group consisted of 56 obese adolescents (26 boys and 30
girls), aged 12 to 18 years, attending the Outpatients Clinic for Children
with Metabolic Disorders. All patients were pubertal (Tanner stage: II
- V), determined by physical examination by a pediatrician according
to the criteria of Tanner. Obesity was recognized on the basis of body
mass index (BMI)>97th percentile for age and sex on BMI percentile
charts for Polish children and adolescents [25]. Patients with syndromal
obesity, infections, cancers, autoimmunologic diseases, hormonal
abnormalities as well as hepatic or renal dysfunction were excluded.
None of the subjects were taking any medications, drinking alcohol or
smoking cigarettes.
The protocol of this study was approved by the Ethical Committee
of the Pomeranian Medical University. Written parental consent and
patient assent was also obtained.
Anthropometric measurements (body weight, height and waist
circumference) were measured by trained staff, with the participants wearing only light underwear and without shoes. Standard, electronic
scale and wall-mounted stadiometer were used to determine body
weight and height. Body mass index (BMI) was calculated by dividing
weight in kilograms by height in meters squared (kg/m2). Since BMI
changes with age, it is expressed as a standard deviation score - SDSBMI
[25]. The minimal abdominal circumference between the xiphoid
process and the iliac crest was measured using the flexible plastic tape,
with the subject standing. As waist circumference changes with age,
the SDS-waist circumference was also calculated [26]. Bioelectrical
impedance analysis was performed in the fasted state using a fixedfrequency
(50 kHz) bioimpedance analysis analyzer (Bioelectrical
Impedance Analyzer Tanita 131, Japan).
All 56 patients initially started in the one-year outpatient
intervention program consisted of caloric restriction supervised by
the study nutritionist, an exercise program developed by exercise
physiologists and behavior therapy including individual psychological
care of the child and his or her family. Nineteen patients wanted to drop
out from the full-intervention program after three weeks, since they
were unable to meet the time commitment to exercise at the gymnasium
5 times/week. At the same time, these patients still declared that they
were ready to continue calorie restriction diet. In order to avoid the
large drop-out from the study, we allowed the adolescents to choose the
type of intervention (diet vs. exercise).
The dietary-treated group (diet group) was prescribed a 500-kcal
deficit diet by the dietitian and received instructions in behavioral
change techniques. Subjects in the diet group met with a nutritionist
once in a week for 3 months after an initial baseline study, and then
once in a month to the end of the study.
Remaining 37 subjects (exercise group) exercised 5 times/week
(45 minutes each time) at the gymnasium under close supervision of
exercise physiologist and at school 2 times/week. Each session was
begun after a warm-up/flexibility exercise that consisted of progressive
stretching for 5 minutes. The aerobic activity involved mainly brisk
walking with movements of total body to ensure maximum caloric
expenditure. Physical training was limited to 20 minutes during the
first week of the study. Then, the duration of activity was progressively
increased so that by the third week the participants were completing
45 minutes of activity per session. Following each training, the subjects
“cooled down” by slow walking for 5 minutes. This moderate physical
activity regimen was supplemented by calorie restriction by exchanging
high-calorie snacks with low-sugar, low-fat snacks and limiting sugarbased
carbonated drinks. Analyses of diet diaries revealed that caloric
deficit was an average 100 kcal/day in this group of patients.
Blood samples were obtained in the fasting state at 8 a.m. and
centrifuged immediately. Determination of serum concentrations
of C-reactive protein (CRP) was performed using a high-sensitivity
assay based on immunoturbidimetric method (Olympus, J). Highsensitivity
enzyme-linked immunosorbent assay (ELISA) was used
for IL-6 (DiaSource, B), FABP-4 (BioVendor, CZ), sICAM-1 and
sVCAM-1 (eBioscience, A). Serum adiponectin was determined by
radioimmunometric (RIA KIT) test (Milipore, Mi, USA).
Glucose was measured with the glucose oxidase technique
(Olympus, J). Free insulin concentration was determined by RIA
(Pharmacia, A). Fasting glucose and insulin concentrations were used
to calculate the homeostasis model assessment for insulin resistance
(HOMA-IR) [27].
Statistical methods
Statistical analyses were performed using the STATA 11 software
package. All data are expressed as mean and standard deviation (± SD).
Kolmogorov-Smirnov non-parametric procedure was used to confirm
the normality distribution assumption for all quantitative variables.
Non-normally distributed variables were log-transformed before
statistical analysis.
Changes in variables were calculated as variable measured at
baseline minus variable measured a year later. They are presented as
mean difference change from baseline (Δ) ± SD.
Correlation analysis between variables before and after intervention
was done using the Pearson’s correlation. Statistically significant
differences were tested for quantitative items by using an independent
sample t test and a one-way ANOVA. For within-group analysis (the
baseline vs. after intervention values) a paired Student’s t test was used.
For among-group comparisons, ANOVA for repeated measures was
used (before and after one year intervention). Covariance analysis
(ANCOVA) was performed to assess the effect of physical activity on
changes in serum concentrations of adipocytokines as well as markers
of inflammation and cell adhesion. ANCOVA was applied when the
ANOVA interaction term was significant. A value of P<0.05 was
considered significant.
Results
There were no significant differences between the two groups at
baseline for all physical and biochemical parameters (Table 1).
Table 1:Clinical and biochemical parameters at baseline and after 1 year of
exercise/dietary intervention.
At baseline, serum concentrations of FABP-4 and sICAM-1 were
significantly higher in the exercise group compared to the diet group
(33.8 ± 13.2 vs. 25.9 ± 14.7 ng/mL, P<0.05; 427.8 ± 103.5 vs. 362.5 ± 85.5
ng/mL, P<0.05, respectively) while adiponectin level was significantly
lower in the exercise group (7.5 ± 2.9 vs. 10.8 ± 4.3 μg/mL, P<0.01) as
shown in table 2 and figure 1b.
Table 2:Circulating markers of inflammation and cell adhesion at baseline and
after 1 year of exercise/dietary intervention.
Figure 1:(a) FABP-4 concentration in exercise and diet groups before and after
1 year of intervention.
(b) Adiponectin concentration in exercise and diet groups before and after 1
year of intervention.
Changes in the variables of interest in response to lifestyle modification in both groups (exercise and dietary group) are presented
in tables 1 and 2 and figures 1a and 1b. There was a statistically
significant improvement in weight, SDS-BMI, %body fat, SDS-waist
circumference, blood pressure as well as plasma insulin concentration
and HOMA-IR after 1 year of lifestyle modification. Additionally, there
was a significant decrease of fasting plasma glucose in the exercise
group. After 1 year, a significant reduction in CRP, IL-6, FABP-4,
sVCAM and increase in adiponectin in both groups were observed.
There was no significant change of sICAM in the diet group. Using
ANOVA to compare the changes (Δ) in the clinical and biochemical
parameters among the two groups, we found statistically significant
differences in all variables, except for diastolic blood pressure and
fasting plasma glucose. Changes in insulin concentration tended to
be higher in the exercise group after the intervention, but were not
statistically significant.
The changes of circulating inflammatory and cell adhesion markers
in correlation to the changes of weight status, percentage body fat, and
waist circumference are shown in table 3. In all 56 patients weight loss
and decreased body fat result in significant decrease in serum levels of CRP, IL-6, FABP-4 as well as cell adhesion molecules, whereas ADN
levels significantly increased.
Table 3:Changes of inflammatory and cell adhesion markers over 1-year period in
correlation to changes of adiposity.
In the “best fit” covariance models (ANCOVA), assessing
relationships between anthropometric and laboratory parameters as
dependent variables with physical exercise or changes of body weight
(as an independent variables), physical activity, independent of changes
in body weight, led to significant improvement in serum levels of
adipocytokines and inflammatory markers (Table 4).
Table 4:Results of co-variance analysis (ANCOVA) with independent variables:
exercise and Δ body weight.
Discussion
The optimal management of obesity starts with a combination
of diet, physical activity, and behavioral modification. Recent studies
demonstrated beneficial effects of exercise training and caloric
restrictions on serum markers of inflammation and cell adhesion after
weight loss in obese adolescents [28,29]. Roberts et al. [30] also showed
that increased oxidative stress markers and pro-inflammatory state
associated with endothelial dysfunction were normalized after shortterm
lifestyle modification programme in obese children. Moreover,
physical exercises are important for preserving lean body mass while
dieting as well as maintaining long-term weight loss. On the other
hand, this “ideal” lifestyle modification is sometimes not accepted
by obese patients, especially by overweight adolescents, and it is the
main reason of dropping out from intervention programs. Therefore,
in this study we compared the effects of physical training and dietary
restriction alone on serum levels of adipocytokines as well as markers
of inflammation and cell adhesion. Our study group consisted of fifty
six obese pubertal children. It is commonly accepted that puberty
influences insulin resistance, inflammation and oxidative stress markers
known to contribute to the development and progression of endothelial
dysfunction [31]. Therefore, obese children who pass through puberty
into adulthood have an increased risk of acceleration of the process of
atherosclerosis [14].
The main finding of the present study is that one year of moderateintensity training reduced elevated levels of inflammatory markers
more than that observed after dietary regimen. After 1 year, the
weight loss as well as improvement in other markers of adiposity was
significantly higher in the exercise group compared to the diet group.
Simultaneously, we found the higher reduction of blood inflammatory
and cell adhesion markers in the exercise group than in the diet group.
Our results are consistent with the results obtained by Tjonna et al.
[32]. In this study, it has been shown that three months of twice-weekly
high-intensity exercise sessions reduced fat mass and induced a more
favourable changes of blood glucose, insulin and adiponectin than
that observed after a traditional, multi treatment strategy, including
exercise, dietary and psychological advice. Follow-up at 12 months
confirmed that this protocol of exercise improved cardiovascular risk
factors to a better degree than traditional obesity intervention program.
Physical activity has shown promising effects as a main therapeutic
tool in obese children, especially in children with metabolic syndrome
[33]. Only a few studies have evaluated the effect of exercise alone,
and their results are controversial. Harmse and Kruger [34] found
significant differences between serum CRP in adolescents in the
different physical activity categories with lower CRP in girls in the
higher physical activity group. Decreases in inflammatory factors in the
group of obese adolescents who underwent 3 months physical activitybased
intervention were reported by Balagopal et al. [35]. Regular
exercise over 6 months has been shown to reverse vascular dysfunction
associated with obesity and improve cardiovascular risk profile with
significant reduction of inflammatory markers in obese adolescents
[36]. It has been found that exercise training modifies body composition
with initial fat loss from the viscera [37]. This would positively affect
the release of pro-inflammatory factors and could explain improved
cardiovascular risk profile after exercise training. In contrast to these
results, Farpour-Lambert et al. [38] reported that physical activity
three times/week for 3 months decreased BMI and body fat, but did
not reduce serum inflammatory factors in pre-pubertal obese children.
Moreover, in the absence of change in body weight, body fat and
abdominal fat, exercise training alone did not improve adipokines
levels [39]. These results indicate that fat reduction (especially visceral
fat) is the main mechanism underlying inflammatory response after
exercises. In the present study, changes of serum inflammatory and cell
adhesion markers were also significantly correlated with weight loss
as well as decreased body fat and waist circumference. Furthermore,
we found that exercise training over one year, reduced serum levels of
CRP, IL-6, sVCAM and improved adipocytokine levels independent of
weight loss.
The appropriate time and intensity of exercise sessions required
to obtain the beneficial effects on subclinical inflammatory state
remains controversial [32,35,36]. It has been shown that in contrast
to acute exercise, long-term exercise training reduces resting levels of
most pro-inflammatory factors, such as CRP, IL-6 and TVF-α [40]. In
obese adults, one year of moderate resistance training has been shown
to improve the inflammatory factors without affecting cell adhesion
molecules [41]. In the present study significant improvement in serum
markers of inflammation and cell adhesion was observed after 6 months
(data not shown) and 1 year of aerobic training. The results of our
study support the hypothesis that 1 year of regular moderate-intensity
exercise training in previously sedentary obese adolescents improves
the adipose-related pro-inflammatory process. It was also found that
this program resulted in a significant increase in the anti-inflammatory
molecule adiponectin and a significant reduction in FABP-4, which
modulates inflammatory cytokine production in macrophages. It is
noteworthy that improvement in serum adipocytokine levels was independent of weight loss. With this, others have demonstrated
significant increases in serum adiponectin levels after exercise training
without changes in body weight or composition [32,42]. Therefore, the
hypothesis that significant weight loss (or loss of body fat) is essential to
alter adiponectin concentrations has not confirmed.
Regarding adipocyte fatty acid-binding protein (FABP-4), this is
the first report, to our knowledge, to characterize the effect of one-year
moderate physical activity on serum concentrations of FABP-4 in obese
adolescents.
An important limitation of the current study is non-randomized
sample. In order to avoid the large drop-out from the study, we allowed
the adolescents to choose the type of intervention (exercise vs. diet). It
is important to note that most of the adolescent boys have chosen the
physical activity as a main therapeutic tool, whereas most of the girls
preferred dietary regimen. A second limitation is the small sample size.
Additional research will be necessary to confirm our findings in a larger
more representative population sample.
The results of this study suggest that regular, moderate-intensity
training is an effective non-pharmacologic intervention to attenuate
low-grade, systemic inflammation in obese adolescents. Further longterm
longitudinal studies are needed to determine whether the exerciseinduced
amendment of inflammatory state in obese adolescents results
in slower development and/or progression of atherosclerosis.
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