Weight loss increased serum adiponectin but decreased lipid levels in obese subjects whose body mass index was lower than 30 kg/m
2Hui-Fen Lang
a,b, Ching-Ya Chou
a,b, Wanye Huey-Herng Sheu
b,⁎ , Jin-Yuarn Lin
a,⁎
aDepartment of Food Science and Biotechnology, National Chung Hsing University, Taichung 40227, Taiwan, Republic of China
bTaichung Veterans General Hospital, Taichung 40705, Taiwan, Republic of China Received 25 January 2011; revised 1 April 2011; accepted 27 April 2011
Abstract
We hypothesized that weight loss in obese subjects may affect adipokine levels, such as adiponectin and tumor necrosis factor (TNF)α. This study investigated the effects of an 8-week weight-control program on serum adiponectin, TNF-α, and blood lipid level profiles in obese subjects. Twenty obese subjects with a body mass index (BMI) higher than 25 kg/m2were recruited for this weight loss program that used dietetic control and aerobic exercise training. A total of 3 obese men and 11 obese women (mean age, 40.3 ± 10.8 years; BMI, 30.0 ± 3.4 kg/m2) finished the program. Anthropometric and biochemical characteristics in subjects before and after the program were determined. The results showed that subjects' body weight, BMI, waist circumference, hip circumference, diastolic blood pressure, total cholesterol, and low-density lipoprotein cholesterol levels significantly (P b.05) decreased during the program. Further analysis showed a negative correlation between delta adiponectin and delta TNF-α, triacylglycerol, and systolic blood pressure in obese subjects. Subgroup analysis showed that obese subjects whose original BMI was less than 30 kg/m2had significantly increased serum adiponectin levels, and more than 3% weight reduction markedly improved blood lipids and body fat profiles during the program. Our findings suggest that weight reduction through an 8-week weight loss program may have anti-inflammatory and antiatherogenic effects via increased serum adiponectin levels and improvements in blood lipid profiles and systolic blood pressure.
© 2011 Elsevier Inc. All rights reserved.
Keywords: Adiponectin body mass index; 8-Week weight-control program; Human; Obese subjects; Tumor necrosis factor-α Abbreviations: BMI, body mass index; CVD, cardiovascular disease; DBP, diastolic blood pressure; GPT, glutamate pyruvate transaminase; HDL, high-density lipoprotein; IL, interleukin; LDL, low-density lipoprotein; SBP, systolic blood pressure; TC, total cholesterol; TG, triacylglycerol; TNF, tumor necrosis factor.
1. Introduction
Obesity may cause chronic diseases including cardiovas- cular disease (CVD) and type 2 diabetes[1]. In addition, in obese rats with acute pancreatitis, obesity alters cytokine
gene expression by increasing proinflammatory tumor necrosis factor (TNF) α levels but decreasing that of anti- inflammatory interleukin (IL)-10 in the pancreas[2]. It was recently found that a higher body mass index (BMI), possibly resulting in abnormal fat deposition in the liver, is related to abnormally high levels of aspartate aminotrans- ferase, alanine aminotransferase, andγ-glutamyl transferase in Taiwanese subjects without chronic hepatitis B or C[3].
Undoubtedly, obesity is linked to inflammation in obese subjects[4]. Excessive adipose cell deposits in the body may start to produce a small amount of proinflammatory
Nutrition Research 31 (2011) 378–386
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⁎ Corresponding authors. Jin-Yuarn Lin is to be contacted at Tel.: +886 4 2285 1857; fax: +886 4 2285 1857. Wanye Huey-Herng Sheu, Tel.: +886 4 2359 2525; fax: +886 4 2359 5046.
E-mail addresses:[email protected](W.H.-H. Sheu), [email protected](J.-Y. Lin).
0271-5317/$–see front matter © 2011 Elsevier Inc. All rights reserved.
doi:10.1016/j.nutres.2011.04.004
cytokines, such as TNF-αand IL-6[5]. These proinflamma- tory cytokines further trigger the accumulation of macro- phages. The recruited macrophages result in TNF-α, IL-6, and monocyte chemoattractant protein-1 overproduction, further resulting in chronic diseases due to long-term inflammatory damage [6]. The prevention of obesity may improve chronic inflammation damage caused by deposited adipose tissues. This study attempted to investigate the effect of weight loss on blood biomarkers and anthropometric and biochemical characteristics in obese subjects via a short-term weight-control program.
Adipose tissue, which expresses a broad spectrum of functional Toll-like receptors, is recognized as immunologic organ producing proinflammatory cytokines, such as IL-6, TNF-α, and chemokines and high amounts of adipokines, such as leptin, adiponectin, and resistin [7]. Among the adipokines, adiponectin and TNF-α play vital roles in inflammation-derived diseases, including atherosclerotic [8] and Alzheimer diseases[9]. Tumor necrosis factor αis produced by different cells, including adipocytes, macro- phages, natural killer cells, and T cells and is involved in systemic inflammation that stimulates the acute phase reaction. In contrast to TNF-α, adiponectin is exclusively produced by adipose tissues and secreted into the blood- stream to modulate metabolic processes including glucose regulation and fatty acid catabolism[10]. Adiponectin may inhibit the proinflammatory cytokines TNF-αand IL-6 and enhance production of the anti-inflammatory cytokine IL-10 by macrophages in vitro [11]. Interestingly, adiponectin production and circulating blood levels are inversely related to body fat content. The secreted levels are dramatically decreased in subjects with diabetes and coronary artery disease[12]. However, modest weight loss does not increase plasma adiponectin levels in overweight-obese subjects[13].
In obese patients, hypoadiponectinemia is an important risk factor for metabolic syndrome [14]and subclinical athero- sclerosis, such as intima-media thickness and arterial compliance [15]. Recently, adiponectin plasma levels were associated with a better metabolic profile because there was reduced cardiac damage and carotid intima-media thickness in patients with chronic kidney disease [16]. Undoubtedly, adiponectin acts as an anti-inflammatory cytokine involved in the metabolic process[17]; however, existing data do not fully elucidate the associations among adiponectin, anthro- pometric, biochemical characteristics, and proinflammatory cytokines in obese subjects during the weight loss process.
We hypothesized that weight loss in obese subjects may affect the adipokines serum levels, such as adiponectin and TNF-α, as well as improve anthropometric and biochemical characteristics. Weight reduction in obese subjects would increase serum adiponectin but decrease TNF-αlevels. The objectives of this study were to examine the effects of an 8- week weight-control program on serum adiponectin, TNF-α, and lipid level profiles in obese subjects and to analyze the associations between selected biomarkers. Subgroup ana- lyses of obese subjects were further categorized by a weight
loss difference of 3% and BMI difference of 30 kg/m2. Based on the experimental evidence, the correlation among adiponectin, anthropometric, biochemical characteristics, and proinflammatory cytokines in obese subjects during the weight loss process will be elucidated.
2. Methods and materials 2.1. Study design
Subjects were recruited to an 8-week weight-control program that combined dietary guidance and aerobic exercise training. The subjects attended class to learn correct dietary guidelines and participated in aerobic exercise for 50 minutes every Saturday during the 8-week program period.
In addition, the subjects were asked to keep a 3-day diet diary (including 1 holiday) in which they recorded everything they ate and drank. A dietitian at the hospital evaluated the 3-day diet record and taught the participants to incorporate low-fat, low-sugar, low-salt, high-fiber, and low-energy foods into their normal diet[18]. The subjects were also encouraged to exercise regularly to increase weight loss.
2.2. Subject selection
This study analyzed the effects of an 8-week weight- control program on serum adiponectin, TNF-α, and lipid levels in obese subjects. Based on the World Health Organization criteria (2004) for android obesity in the Asia-Pacific region [19], android obese subjects were recruited for the program at Taichung Veterans General Hospital, Taiwan, Republic of China. The study subjects had a BMI of 25 kg/m2or greater and waist circumference of 90 cm or more for men and 80 cm or more for women. All subjects were older than 18 years. Twenty participants ranging in age from 20 to 55 years were enrolled in the program (May 2006–May 2007). All applicable institutional and governmental regulations concerning the ethical use of human volunteers were approved by the institutional review board of Taichung Veterans General Hospital at the 61st committee meeting of the institutional review board. The subjects were advised of the study and provided written consent. At the initial screening, subjects having CVD, acute or chronic infections, inflammation, endocrine or thyroid secretion disorders, diabetes, or pregnancy, or those taking medicines for hypertension, inflammation, or obesity were excluded from this study. The daily activity of the participant subjects was categorized as sedentary for 1 year, with body weight changes of less than 5 kg during the 3 months before the weight-control program. Fourteen obese subjects includ- ing 3 men and 11 women were qualified for this study. Their average age was 40.3 ± 10.8 years, and their BMI was 30.0 ± 3.4 kg/m2. Anthropometric evaluations were performed using traditional methods. To compare the effects of the 8- week weight-control program on anthropometric and biochemical characteristics in obese subjects, collected data were further divided into subgroups, including weight loss of
less than 3% vs weight loss of 3% or more and original BMI of less than 30 kg/m2vs 30 kg/m2or higher, for comparison.
2.3. Assessment
Changes in weight loss, waist circumference, body fat, blood pressure, fasting plasma glucose level, serum lipid profiles, and TNF-αand adiponectin levels were calculated as the difference between the participant subjects' baseline (week 0) values and values during the last week of attendance (week 8). Fasting blood samples from subjects were collected at the beginning (week 0) and at the end of week 8. The blood was drawn for plasma and serum preparations. Anthropo- metric measurements were conducted weekly. Waist circum- ference was measured with the subject standing. A tape was placed in a horizontal plane at the level of the iliac crest without compressing the skin. Using a digital mercury sphygmomanometer, blood pressure was measured twice from the right arm with a correctly fitted cuff after the patient sat quietly for 5 minutes[20]. The mean blood pressure was used for evaluation. Plasma fasting glucose levels and serum lipids levels including triacylglycerol (TG), total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, high- density lipoprotein (HDL) cholesterol, and other selected biochemical characteristics were processed by the Central Laboratory Services at Taichung Veterans General Hospital using enzymatic methods[21]. The body fat was measured with a machine using tetrapolar segmental bioelectrical impedance analysis (Zeus 9.9 Jawon Medical Co Ltd, Seoul, Korea). Baseline data were collected within 1 week before the program's start. Postprogram samples were obtained within 1 week after the program finished[20].
Serum adiponectin and TNF-α levels were determined using sandwich enzyme-linked immunosorbent assay (ELISA) kits. The adiponectin concentration was assayed using an ELISA kit (Quantikine Human adiponectin; R&D Systems, Inc, Minneapolis, Minn). The TNF-α concentra- tions were assayed using high-sensitivity ELISA kits (Quantikine HS Human TNF-α; R&D Systems, Inc). The adiponectin assay was sensitive to levels of about less than 15.6 pg/mL. The TNF-α assay was sensitive to about less than 0.039 pg/mL. Serum adiponectin and TNF-α concen- trations were assayed according to the cytokine ELISA protocol in the manufacturer's instructions[22]. The plates were measured by recording absorbance at 450 nm using a plate reader (ELISA reader; Asys Hitech, GmbH, Salzburg, Austria). The serum adiponectin and TNF-α levels were determined using a 7-point standard.
2.4. Statistical analyses
Values were expressed as means ± SD. Data were first analyzed using the Kolmogorov-Smirnov test to recognize a normal distribution, followed by the Pearson correlation for a 2-tailed test between 2 variables. In all subjects, differences between the beginning and posttreatment measurements were analyzed using the paired Studentttest. Intrasubgroup
changes between the beginning and posttreatment periods were analyzed using the Wilcoxon signed rank test.
Intersubgroup changes through the program period were analyzed using the Mann-Whitney U test. Differences between groups were considered statistically significant if Pb.05. Statistical tests were performed using SPSS version 10.1 (SPSS, Chicago, Ill).
3. Results
3.1. Basic characteristics of participant subjects
To characterize participants in the program, anthropo- metric and biochemical characteristics were surveyed before and after the 8-week weight-control program (Table 1). Most of the anthropometric characteristics in the obese subjects, including body weight, BMI, waist and hip circumferences, diastolic blood pressure (DBP), body lean and fat masses, and subcutaneous fat mass, were significantly improved through the 8-week program (P b .05). All obese subjects experienced a marked decrease in body weight during the program (data not shown). Among the selected biochemical
Table 1
Anthropometric and biochemical characteristics of all obese subjects before and after the 8-week weight-control program
Weight-control program Pa
Before After
Anthropometric characteristics
n (men/women) 14 (3/11) 14 (3/11)
Age (y) 40.3 ± 10.8 40.3 ± 10.8
Body weight (kg) 77.5 ± 10.0 75.0 ± 9.5 .000⁎
Weight change -2.5 ± 1.7
BMI (kg/m2) 30.0 ± 3.4 29.3 ± 3.2 .001⁎
Waist circumference (W) (cm) 100 ± 8 96 ± 6 .005⁎ Hip circumference (H) (cm) 107 ± 7 104 ± 7 .000⁎
W/Hratio 0.94 ± 0.04 0.92 ± 0.04 .249
SBP (mm Hg) 125 ± 13 121 ± 15 .326
DBP (mm Hg) 77.8 ± 11.3 72.9 ± 10.3 .039⁎
Body lean mass (kg) 46.0 ± 6.8 45.0 ± 6.3 .001⁎ Body fat mass (kg) 26.4 ± 5.0 25.3 ± 5.0 .008⁎ Visceral fat mass (kg) 4.3 ± 1.0 4.1 ± 1.0 .029⁎ Body fat composition (%) 34.4 ± 4.2 33.9 ± 4.3 .130 Subcutaneous fat mass (kg) 22.1 ± 4.0 21.2 ± 4.0 .006⁎ Biochemical characteristics
Fasting glucose (mg/dL) 89.6 ± 9.4 87.3 ± 8.2 .160
TC (mg/dL) 210 ± 33 194 ± 28 .001⁎
TG (mg/dL) 163 ± 93 158 ± 81 .590
HDL cholesterol (mg/dL) 48.1 ± 9.4 45.7 ± 7.9 .360 LDL cholesterol (mg/dL) 131 ± 23 116 ± 22 .004⁎
TC/HDL 4.6 ± 1.2 4.4 ± 1.2 .279
LDL/HDL 2.9 ± 0.9 2.7 ± 1.2 .155
Creatinine (mg/dL) 0.9 ± 0.2 0.9 ± 0.2 .844
GPT (U/L) 31.4 ± 16.4 30.1 ± 15.7 .631
Adiponectin (μg/mL) 1.5 ± 0.5 1.6 ± 0.6 .311
TNF-α(pg/mL) 1.2 ± 0.5 1.3 ± 0.6 .457
Values are means ± SD. GPT, glutamate pyruvate transaminase.
a Statistical significance was assayed by Wilcoxon signed rank test between before and after the weight-control program.
⁎ Pb.05.
characteristics, TC and LDL cholesterol levels in obese subjects were significantly decreased through the 8-week program (Pb.05). However, other biochemical biomarkers including serum adiponectin and TNF-α levels did not significantly change during the program (PN.05).
Gender difference in body fat content is well known;
however, in this study, some important biochemical charac- teristics were further grouped by gender difference. Interest- ingly, body fat composition and serum TG levels showed significant differences between male and female obese subjects (Table 2). Female obese subjects had significantly higher body fat composition but lower serum TG levels. The weight loss process did not significantly change but slightly decreased (P N .05) body fat composition and serum TG levels in female subjects (Table 2). Serum TG levels in male obese subjects significantly decreased throughout the program. We conjectured that the higher TG levels (N200 mg/dL) were more easily decreased by weight loss. We further discovered that the change patterns of most selected biomarkers, including adiponectin and TNF-α, in either female or male obese subjects were quite similar during the weight loss process (Table 2); thus, we pooled all data from both sexes to minimize the possible deviation due to the limited number of obese men (3) in this study.
3.2. Associations among net changes in serum adiponectin, TNF-α, and selected characteristics in obese subjects during the program
To determine the correlations among net changes in serum anti-inflammatory (Δadiponectin) and proinflamma- tory (ΔTNF-α) mediators and selected characteristics in obese subjects during the program, associations among Δadiponectin, ΔTNF-α, and net changes in selected
characteristics in subjects before and after the weight-control program were analyzed (Table 3). SerumΔadiponectin in all obese subjects showed statistically (P b .05) negative correlations withΔTG (r=−0.582, P= .029) andΔTNF- α (r = −0.627, P = .016), suggesting that an increased adiponectin level may decrease blood TG and TNF-αlevels.
A statistically positive correlation was found between ΔTNF-α and Δsystolic blood pressure (SBP; r = 0.552, P = .041), suggesting that higher TNF-α levels are associated with higher SBP. Net change in TNF-α also exhibited statistically (P b .05) positive correlations with ΔTG (r= 0.547,P = .043), suggesting that the higher the TNF-α level, the higher the TG level. However, there was no significant association among the net changes in other selected obese subject characteristics.
3.3. Effects of an 8-week weight-control program on anthropometric and selected biochemical characteristics in obese subject subgroups categorized by weight loss differences of 3%
To evaluate the effects of the 8-week weight-control program on anthropometric and selected biochemical characteristics in obese subject subgroups categorized by weight loss differences of 3%, the data collected were further subdivided into 2 subgroups (Table 4). The results showed that weight and hip circumference in obese subjects significantly decreased when weight loss was less than 3%
(Pb.05, n = 6) during the program. However, weight, BMI,
Table 2
Selected biochemical characteristics in female and male obese subjects before and after the 8-week weight-control program
Weight-control program Pa
Before After
Female subjects
n (women subjects) 11 11
Age (y) 38.6 ± 11.5 38.6 ± 11.5
Body fat composition (%) 36.2 ± 2.4 35.6 ± 2.7 .117
TG (mg/dL) 132 ± 70 129 ± 55 .829
Adiponectin (μg/mL) 1.6 ± 0.5 1.7 ± 0.7 .208
TNF-α(pg/mL) 1.1 ± 0.5 1.2 ± 0.6 .669
Male subjects
n (men subjects) 3 3
Age (y) 46.3 ± 5.0 46.3 ± 5.0
Body fat composition (%) 27.8 ± 1.8 27.4 ± 2.3 .539
TG (mg/dL) 277 ± 81 262 ± 83 .006⁎
Adiponectin (μg/mL) 1.3 ± 0.2 1.2 ± 0.3 .794
TNF-α(pg/mL) 1.4 ± 0.4 1.7 ± 0.5 .175
Values are means ± SD.
a Statistical significance was assayed by paired Studentttest between before and after the weight-control program.
⁎ Pb.05.
Table 3
Associations among net changes in adiponectin and TNF-αlevels and net changes in different characteristics in all obese subjects during the 8-week weight-control program
Net changes in characteristics
R
ΔAdiponectin ΔTNF-α
ΔSBP −0.355 0.552⁎
ΔDBP 0.107 −0.361
ΔWeight −0.081 −0.006
ΔBMI 0.014 −0.036
ΔWaist circumference (W) 0.061 −0.110
ΔHip circumference (H) −0.273 0.272
ΔW/Hratio 0.115 −0.172
ΔFasting glucose −0.177 0.518
ΔTC −0.031 0.113
ΔTG −0.582⁎ 0.547⁎
ΔHDL cholesterol 0.452 −0.233
ΔLDL cholesterol 0.178 −0.133
ΔGPT 0.075 −0.050
ΔAdiponectin 1 −0.627⁎
ΔTNF-α −0.627⁎ 1
ΔBody lean mass 0.236 0.038
ΔBody fat mass −0.300 0.023
ΔVisceral fat mass −0.203 −0.064
ΔBody fat composition −0.330 0.023
ΔSubcutaneous fat −0.331 0.054
Δindicates net changes in parameters in participant subjects over the course of the program; GPT, glutamate pyruvate transaminase.
⁎ Pb.05.
Table 4
Effects of the weight-control program on anthropometric and selected biochemical characteristics in obese subjects categorized by a weight loss difference of 3%
Characteristics Program treatment Groups Pa
Weight lossb3%
(n = 6; 1 male, 5 female)
Weight loss≥3%
(n = 8; 2 male, 6 female)
Weight (kg) Before 73.3 ± 9.8 80.7 ± 9.5 .245
After 72.1 ± 9.6 77.1 ± 9.5 .366
Change −1.1 ± 0.7 −3.6 ± 1.4 .002⁎
Pb .028⁎ .012⁎
BMI (kg/m2) Before 29.2 ± 2.8 30.7 ± 3.8 .606
After 28.9 ± 2.9 29.6 ± 3.6 1
Change −0.2 ± 0.4 −1.1 ± 0.4 .003⁎
Pb .249 .012⁎
DBP (mm Hg) Before 78.2 ± 12.5 77.5 ± 11.3 1
After 77.8 ± 10.1 69.3 ± 9.3 .135
Change −0.3 ± 8.9 −8.3 ± 5.4 .092
Pb .833 .012⁎
Waist circumference (cm) Before 98 ± 9 101 ± 8 .399
After 97 ± 6 96 ± 7 .897
Change −2 ± 5 −5 ± 2 .193
Pb .344 .012⁎
Hip circumference (cm) Before 105 ± 9 108 ± 5 .243
After 103 ± 8 105 ± 6 .401
Change −2 ± 1 −3 ± 2 .396
Pb .042⁎ .012⁎
Body fat mass (kg) Before 24.8 ± 3.7 27.6 ± 5.7 .332
After 24.7 ± 4.8 25.7 ± 5.5 .747
Change −0.2 ± 1.2 −1.9 ± 1.0 .014⁎
Pb .753 .012⁎
Visceral fat mass (kg) Before 4.0 ± 0.7 4.5 ± 1.2 .475
After 4.0 ± 1.0 4.1 ± 1.1 .948
Change 0.0 ± 0.4 −0.4 ± 0.3 .027⁎
Pb .752 .018⁎
Body fat composition (%) Before 34.2 ± 2.7 34.5 ± 5.2 .606
After 34.3 ± 3.6 33.5 ± 5.0 .897
Change 0.1 ± 1.4 −1.0 ± 1.0 .137
Pb .753 .036⁎
Subcutaneous fat mass (kg)
Before 20.8 ± 3.0 23.0 ± 4.6 .366
After 20.7 ± 3.8 21.6 ± 4.4 .651
Change −0.2 ± 0.9 −1.5 ± 0.8 .009⁎
Pb .752 .012⁎
Adiponectin (μg/mL) Before 1.5 ± 0.5 1. 5 ± 0.5 .796
After 1. 6 ± 0.7 1.6 ± 0.6 .519
Change 0.1 ± 0.3 0.1 ± 0.4 .796
Pb .463 .401
TNF-α(pg/mL) Before 1.3 ± 0.4 1.1 ± 0.5 .302
After 1.3 ± 0.5 1.3 ± 0.7 .897
Change −0.1 ± 0.3 0.2 ± 0.3 .156
Pb .463 .161
TC (mg/dL) Before 219 ± 42 203 ± 26 .897
After 207 ± 29 184 ± 24 .137
Change −12 ± 19 −19 ± 2 .245
Pb .116 .012⁎
LDL cholesterol (mg/dL) Before 139 ± 27 122 ± 18 .302
After 130 ± 23 106 ± 17 .05
Change −9 ± 18 −15 ± 5 .121
Pb .249 .012⁎
HDL cholesterol (mg/dL) Before 43.5 ± 5.3 51.5 ± 10.6 .153
After 42.5 ± 6.5 48.1 ± 8.4 .27
Change −1.0 ± 4.5 −3.4 ± 3.1 .243
Pb .5 .034⁎
Values are means ± SD.
a Statistical significance was assayed by Mann-WhitneyUtest between groups categorized by a weight loss of 3% during the program.
b Statistical significance was assayed by Wilcoxon signed rank test between before and after the weight-control program.
⁎ Pb.05.
DBP, waist and hip circumference, body fat mass, visceral fat mass, body fat composition, subcutaneous fat mass, TC, LDL, and HDL in obese subjects markedly decreased when the weight loss was 3% or more (P b.05, n = 8). The net changes in weight, BMI, body fat mass, visceral fat mass, and subcutaneous fat mass were significantly different between the 2 subgroups (P b .05). Unfortunately, serum adiponectin and TNF-αlevels did not significantly change in the 2 subgroups (P N .05) after the 8-week weight-control program (Table 4).
3.4. Effects of the 8-week weight-control program on anthropometric and selected biochemical characteristics in obese subject subgroups categorized by original BMI values To further evaluate the effects of the 8-week weight- control program on anthropometric and selected biochemical characteristics in obese subject subgroups, based on their initial BMI values, data were further subdivided into 2 subgroups: those with an initial BMI of less than 30 kg/m2 and those with an initial BMI of 30 kg/m2 or greater (Table 5). The results showed that weight, BMI, hip circumference, body fat mass, visceral fat mass, body fat composition, subcutaneous fat mass, TC, and LDL in obese subjects decreased significantly (P b .05). Importantly, serum adiponectin levels in obese subjects with an initial BMI of less than 30 kg/m2(n = 9) markedly increased during the program (P b.05), whereas, weight circumference and serum TNF-α levels did not significantly change. Weight, BMI, waist and hip circumference, TC, and LDL in obese subjects with an initial BMI of 30 kg/m2or greater (n = 5) markedly decreased (Pb.05). Interestingly, the net change in serum adiponectin levels was significantly different between the 2 subgroups (P b .05; +0.3 ± 0.3 vs −0.2 ± 0.2 μg/mL). Serum TNF-α levels did not significantly change in the 2 subgroups (PN.05) (Table 5).
4. Discussion
There is considerable evidence proving the beneficial effect of weight loss on the metabolic profile. This study found that an 8-week weight loss program did lead to improvements in most of the anthropometric and biochem- ical characteristics evaluated in obese patients. Both diet and exercise modifications were adopted in this program. The results are significant and in accordance with previous studies. Hellenius et al[23]reported that changes in diet and exercise via lifestyle modifications for 1 year are equally effective in reducing the risk of CVD. Weight loss of up to 5% to 10% is the primary strategy for preventing obesity- related diseases such as CVD and type 2 diabetes [24].
Unfortunately, only a 3.23% reduction in the body weight of subjects was achieved during this study's 8-week weight- control program. This study suggests that a long-term weight-control program and lifestyle modifications may be more effective in reducing the weight of obese subjects.
Table 5
Effects of the weight-control program on anthropometric and selected biochemical characteristics in obese subject categorized by the BMI difference at 30 kg/m2
Characteristics Program treatment
Groups Pa
BMIb30 kg/m2 (n = 9; 2 male, 7 female)
BMI≥30 kg/m2 (n = 5; 1 male, 4 female)
Weight (kg) Before 72.5 ± 7.5 86.6 ± 7.4 .014⁎ After 69.9 ± 7.0 84.1 ± 5.9 .006⁎ Change −2.6 ± 1.8 −2.4 ± 1.7 .894
Pb .008⁎ .043⁎
BMI (kg/m2) Before 28.0 ± 1.2 33.6 ± 3.0 .003⁎ After 27.4 ± 1.3 32.8 ± 2.5 .003⁎ Change −0.7 ± 0.6 −0.8 ± 0.7 .841
Pb .021⁎ .043⁎
Waist
circumference (cm)
Before 95 ± 5 109 ± 4 .003⁎
After 93 ± 4 103 ± 4 .005⁎
Change −2 ± 5 −6 ± 2 .019⁎
Pb .084 .042⁎
Hip circumference (cm)
Before 103 ± 5 113 ± 5 .006⁎
After 100 ± 4 111 ± 5 .004⁎
Change −3 ± 2 −2 ± 1 .345
Pb .011⁎ .043⁎
Body fat mass (kg) Before 23.8 ± 2.5 31.0 ± 5.2 .008⁎ After 22.3 ± 2.5 30.5 ± 4.1 .006⁎ Change −1.5 ± 1.0 −0.5 ± 1.8 .317
Pb .011⁎ .686
Visceral fat mass (kg)
Before 3.8 ± 0.6 5.2 ± 1.1 .009⁎
After 3.5 ± 0.6 5.1 ± 0.8 .006⁎
Change −0.3 ± 0.3 −0.1 ± 0.5 .383
Pb .012⁎ .715
Body fat composition (%)
Before 33.5 ± 3.7 36.1 ± 4.9 .205 After 32.4 ± 3.9 36.4 ± 4.2 .039⁎ Change −1.0 ± 0.8 0.4 ± 1.4 .061
Pb .015⁎ .686
Subcutaneous fat mass (kg)
Before 20.0 ± 2.1 25.8 ± 4.1 .009 After 18.9 ± 2.0 25.4 ± 3.3 .005 Change −1.2 ± 0.8 −1.5 ± 0.8 .283
Pb .011⁎ .5
Adiponectin (μg/mL)
Before 1.7 ± 0.5 1. 2 ± 0.1 .125
After 1.9 ± 0.6 1.0 ± 0.2 .014⁎
Change 0.3 ± 0.3 −0.2 ± 0.2 .014⁎
Pb .028⁎ .08
TNF-α(pg/mL) Before 1.0 ± 0.5 1.5 ± 0.4 .125
After 1.1 ± 0.6 1.7 ± 0.3 .028⁎
Change 0.0 ± 0.3 0.2 ± 0.3 .317
Pb .859 .138
TC (mg/dL) Before 215 ± 39 200 ± 21 .463
After 197 ± 30 189 ± 26 .689
Change −18 ± 15 −12 ± 10 .286
Pb .011⁎ .043⁎
LDL (mg/dL) Before 127 ± 26 133 ± 18 .463
After 114 ± 21 121 ± 27 .739
Change −13 ± 14 −12 ± 10 .947
Pb .038⁎ .043⁎
Values are means ± SD.
a Statistical significance was assayed by Mann-WhitneyUtest between groups categorized by the BMI differences at 30 kg/M2before the program.
b Statistical significance was assayed by Wilcoxon signed rank test between before and after the weight-control program.
⁎ Pb.05.
Total and LDL cholesterol levels in obese subjects were significantly (P b .05) decreased during the program, suggesting that even a slight decrease in body weight significantly improved blood lipid profiles. Previous studies indicated that weight loss may reduce increased blood glucose levels and insulin resistance[25, 26]. However, there was no significant weight loss effect on blood glucose levels in the obese subjects in this study. We hypothesize that this may be because all of the subjects had normal glucose levels before treatment; thus, their weight loss did not significantly affect their fasting glucose levels. These obese subjects were normoglycemic patients with borderline cardiovascular risk factors. The weight loss did improve but failed to completely correct all risk factors. However, significant decreases in DBP and total and LDL cholesterol during the weight loss process are beneficial for the health state of the subjects and alleviate the risk of CVD.
Obese individuals often experience chronic inflammation.
Excessive human adipose tissue may cause a variety of inflammation-derived diseases [27]. Chronic inflammation can be generally defined as the local accumulation of fluid, plasma proteins, and white blood cells resulting from physical injury, infection, or a local immune response[28].
Recently, adiponectin has attracted focus for its anti- inflammatory and antiatherogenic effects, and its receptors are expressed in many human tissues, including adipose tissues and the liver[29]. Increased serum adiponectin levels have potential therapeutic benefits in nonalcoholic fatty liver disease[30]. We found that serumΔadiponectin in all obese subjects had statistically (Pb.05) negative correlations with ΔTG andΔTNF-α. Our results are in accordance with those of previous studies and suggest that increased adiponectin levels decreased blood TG and TNF-αlevels[31]. Decreased blood TG and TNF-αlevels may further decrease the risk of CVD and chronic inflammation. Adiponectin may decrease monocyte adhesion by inhibiting endothelial nuclear factor κB signaling through a cyclic adenosine monophosphate– dependent pathway in vitro [32]. We also found a statistically (Pb.05) positive correlation betweenΔTNF-α andΔSBP in obese subjects. This study further suggests that increased adiponectin levels may decrease SBP in obese subjects by decreasing serum TNF-αlevels. The results may be relevant to hypertension therapy.
Our primary purpose was to decrease body weight and improve anthropometric and biochemical characteristics in obese subjects through the 8-week weight-control program.
As expected, the program significantly improved some characteristics in the subjects. However, variations in the magnitude of weight loss and in the original BMI of obese subjects may have different effects on anthropometric and biochemical characteristics. The subgroup analysis showed that the weight loss program led to significantly increased serum adiponectin levels in obese subjects whose BMI was less than 30 kg/m2(Pb.05), but decreased body fat mass, visceral fat mass, body fat composition, and subcutaneous fat mass, compared with subjects with a BMI of 30 kg/m2 or
greater. Importantly, the net weight loss (−2.6 kg) in subjects whose BMI was less than 30 kg/m2 was higher than that (−2.4 kg) in subjects with a BMI of 30 kg/m2or greater. We assume that the higher weight loss might be attributed to the increased adiponectin levels. Our results suggest that it is more difficult to improve the obesity-related biomarkers of obese subjects whose BMI is higher than 30 kg/m2. We suggest that subjects with a BMI of 30 kg/m2or greater may develop hyperplastic obesity, which causes greater difficulty in losing weight and increases the concentrations of the obesity-related biomarkers. More studies are needed to elucidate the reason for these changes. A weight reduction of 3% or more significantly (Pb.05) improved blood lipids and body fat profiles but did not significantly (Pb.05) increase serum adiponectin levels. Taken together, the results suggest that weight loss in obese subjects with an initial BMI of less than 30 kg/m2 and a weight reduction of 3% or more may have better effects on adiponectin, blood lipids, and body fat profiles.
In this study, serum adiponectin and TNF-αlevels of all subjects did not significantly change during the program (PN .05). A short-term, 14-week study found that a 4.5-kg weight loss through dietary control and exercise training decreased C-reactive protein and leptin levels but did not markedly affect adiponectin and TNF-α levels [33]. Polak et al [34]
reported that a 5.9% weight reduction through a 12-week aerobic training regimen decreased the waist-to-hip ratio and leptin levels and increased insulin sensitivity but did not significantly change adiponectin and TNF-αlevels. Howev- er, a very low-energy diet, 24-week weight-control program decreased the body weight of subjects by 20 kg. Serum adiponectin levels were significantly increased in subjects, but TNF-αlevels decreased[26]. Esposito et al[35]reported that lifestyle modification by obese subjects for a period of 2 years led to decreased body weight and C-reactive protein but increased adiponectin levels. Adiponectin secretion may be inhibited by obesity through a feedback loop [36]. It is suggested that long-term treatment periods may be necessary to modulate the feedback inhibition process. In addition, Nicklas et al [37] reported that TNF-α levels in obese subjects may be significantly decreased by weight loss through lifestyle modification for 12 months. We suggest that significant weight loss and a long-term weight-control program are necessary to modulate adiponectin and TNF-α levels in obese subjects. The hypothesis of this study might be accepted; however, the mechanism by which dietary control and exercise training regulate the inflammation- regulated immune response during weight loss requires further study.
There are some limitations to this study. First, the number of subjects (n = 14) was small. Second, an 8-week weight loss program is too short for significant weight reduction.
Long-term studies with larger study samples should be conducted. However, we achieved some important results.
Undoubtedly, obesity is the most important risk for the development of diabetes and predisposes individuals to
hypertension and dyslipidemia[38]. This study revealed that a short-term weight-control program for obese individuals may have anti-inflammatory and antiatherogenic effects via increasing serum adiponectin levels, especially in obese subjects whose BMI was lower than 30 kg/m2, while decreasing TG and SBP levels.
In summary, our results demonstrated that the 8-week weight-control program significantly decreased body weight, BMI, waist and hip circumference, TC, and LDL cholesterol in obese subjects. Subgroup analysis further revealed better outcomes in terms of adiponectin levels, blood lipids, and body fat profiles in obese subjects with a BMI of less than 30 kg/m2and a weight loss of 3% or more.
The present study suggests that a short-term weight-control program may have anti-inflammatory and antiatherogenic effects by increasing serum adiponectin levels in obese subjects whose BMI was lower than 30 kg/m2and improving blood lipid profiles and SBP in obese individuals.
Acknowledgment
This study was kindly supported by research grants NSC95-2313-B-005-059 from the National Science Council and Institutional Review Board TCVGH No. C05082/561 from the Taichung Veterans General Hospital, Taichung, Taiwan, Republic of China.
References
[1] Ford ES, Williamson DF, Liu S. Weight change and diabetes incidence: findings from a national cohort of US adults. Am J Epidemiol 1997;146:214-22.
[2] Segersvard R, Tsai JA, Herrington MK, Wang F. Obesity alters cytokine gene expression and promotes liver injury in rats with acute pancreatitis. Obesity 2008;16:23-8.
[3] Hsieh MH, Ho CK, Hou NJ, Hsieh MY, Lin WY, Yang JF, et al.
Abnormal liver function test results are related to metabolic syndrome and BMI in Taiwanese adults without chronic hepatitis B or C. Int J Obes 2009;33:1309-17.
[4] Sumarac-Dumanovic M, Stevanovic D, Ljubic A, Jorga J, Simic M, Stamenkovic-Pejkovic D, et al. Increased activity of interleukin-23/
interleukin-17 pro-inflammatory axis in obese women. Int J Obes 2009;33:151-6.
[5] Tataranni PA, Ortega E. A burning question: does an adipokine- induced activation of the immune system mediate the effect of overnutrition on type 2 diabetes? Diabetes 2005;54:917-27.
[6] Fantuzzi G. Adipose tissue, adipokines, and inflammation. J Allergy Clin Immunol 2005;115:911-9.
[7] Schafler A, Scholmerich J, Salzberger B. Adipose tissue as an immunological organ: Toll-like receptors, C1q/TNFs and CTRPs.
Trends Immunol 2007;28:393-9.
[8] Shimada K, Miyazaki T, Daida H. Adiponectin and atherosclerotic disease. Clin Chim Acta 2004;344:1-12.
[9] Swardfager W, Lanctot K, Rothenburg L, Wong A, Cappell J, Herrmann N. A meta-analysis of cytokines in Alzheimer's disease.
Biol Psychiatry 2010;68:930-41.
[10] Diez JJ, Iglesias P. The role of the novel adiponectin-derived hormone adiponectin in human disease. Eur J Endocrinol 2003;148:293-300.
[11] Kumada M, Kihara S, Ouchi N, Kobayashi H, Okamoto Y, Ohashi K, et al. Adiponectin specifically increased tissue inhibitor of metallo-
proteinase-1 through interleukin-10 expression in human macro- phages. Circulation 2004;109:2046-9.
[12] Whitehead JP, Richards AA, Hickman IJ, Macdonald GA, Prins JB.
Adiponectin-a key adipokine in the metabolic syndrome. Diabetes Obes Metab 2006;8:264-80.
[13] Shin MJ, Kim OY, Koh SJ, Chae JS, Kim JY, Jang Y, et al. Modest weight loss does not increase plasma adiponectin levels: effects of weight loss on C-reactive protein and DNA damage. Nutr Res 2006;26:
391-6.
[14] Renaldi O, Pramono B, Sinorita H, Purnomo LB, Asdie RH, Asdie AH. Hypoadiponectinemia: a risk for metabolic syndrome. Acta Med Indones 2009;41:20-4.
[15] Shargorodsky M, Boaz M, Goldberg Y, Matas Z, Gavish D, Fux A, et al. Adiponectin and vascular properties in obese patients: is it a novel biomarker of early atherosclerosis? Int J Obes 2009;33:553-8.
[16] Norata GD, Baragetti I, Raselli S, Stucchi A, Garlaschelli K, Vettoretti S, et al. Plasma adiponectin levels in chronic kidney disease patients:
relation with molecular inflammatory profile and metabolic status.
Nutr Metab Cardiovasc Dis 2010;20:56-63.
[17] Tsataanis C, Zacharioudaki V, Androulidaki A, Dermitzaki E, Charalampopoulos I, Minas V, et al. Adiponectin induces TNF-alpha and IL-6 in macrophages and promotes tolerance to itself and other pro-inflammatory stimuli. Biochem Biophys Res Commun 2005;335:
1254-63.
[18] Culling KS, Neil HAW, Gilbert M, Frayn KN. Effects of short-term low- and high-carbohydrate diets on postprandial metabolism in non- diabetic and diabetic subjects. Nutr Metab Cardiovasc Dis 2009;19:
345-51.
[19] Expert Panel WHO. Appropriate body-mass index for Asian popula- tions and its implications for policy and intervention strategies. Lancet 2004;363:157-63.
[20] Lundgren JD, Malcolm B, Binks M, O'Neil PM. Remission of metabolic syndrome following a 15-week low-calorie lifestyle change program for weight loss. Int J Obes 2009;33:144-50.
[21] Lin JY, Lu S, Liou YL, Liou HL. Antioxidant and hypolipidaemic effects of a novel yam-boxthorn noodle in an in vivo murine model.
Food Chem 2006;94:377-84.
[22] Lin JY, Li CY, Hwang IF. Characterization of the pigment components in red cabbage (Brassica oleracea L. var.) juice and their anti- inflammatory effects on LPS-stimulated murine splenocytes. Food Chem 2008;109:771-81.
[23] Hellenius ML, de Faire U, Berglund B, Hamsten A, Krakau I. Diet and exercise are equally effective in reducing risk for cardiovascular disease. Results of a randomized controlled study in men with slightly to moderately raised cardiovascular risk factors. Atherosclerosis 1993;
103:81-91.
[24] Suastika K. Update in the management of obesity. Acta Med Indones 2006;38:231-7.
[25] Baratta R, Amato S, Degano C, Farina MG, Patane G, Vigneri R, et al.
Adiponectin relationship with lipid metabolism is independent of body fat mass: evidence from both cross-sectional and intervention studies.
J Clin Endocrinol Metab 2004;89:2665-71.
[26] Bruun JM, Lihn AS, Verdich C, Pedersen SB, Toubro S, Astrup A, et al. Regulation of adiponectin by adipose tissue-derived cytokines: in vivo and in vitro investigations in humans. Am J Physiol Endocrinol Metab 2003;285:E527-33.
[27] O'Rourke RW, Metcalf MD, White AE, Madala A, Winters BR, Maizlin II, et al. Depot-specific differences in inflammatory mediators and a role for NK cells and IFN-γin inflammation in human adipose tissue. Int J Obes 2009;33:978-90.
[28] Lin JY, Li CY. Proteinaceous constituents of red cabbage juice increase IL-10, but decrease TNF-αsecretions using LPS-stimulated mouse splenocytes. J Food Drug Anal 2010;18:15-23.
[29] Kos K, Wong SPY, Huda MSB, Cakir M, Jernas M, Carlsson L, et al.
In humans the adiponectin receptor R2 is expressed predominantly in adipose tissue and linked to the adipose tissue expression of MMIF-1.
Diabetes Obes Metab 2010;12:360-3.
[30] Polyzos SA, Kountouras J, Zavos C, Tsiaousi E. The role of adiponectin in the pathogenesis and treatment of non-alcoholic fatty liver disease. Diabetes Obes Metab 2010;12:365-83.
[31] Xydakis AM, Case CC, Jones PH, Hoogeveen RC, Liu MY, Smith EO, et al. Adiponectin, inflammation, and the expression of the metabolic syndrome in obese individuals: the impact of rapid weight loss through caloric restriction. J Clin Endocrinol Metab 2004;89:
2697-703.
[32] Ouchi N, Kihara S, Arita Y, Okamoto Y, Maeda K, Kuriyama H, et al.
Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF-kappaB signaling through a cAMP-dependent pathway. Circula- tion 2000;102:1296-301.
[33] Giannopoulou I, Fernhall B, Carhart R, Weinstock RS, Baynard T, Figueroa A, et al. Effects of diet and/or exercise on the adipocytokine and inflammatory cytokine levels of postmenopausal women with type 2 diabetes. Metabolism 2005;54:866-75.
[34] Polak J, Klimcakova E, Moro C, Viguerie N, Berlan M, Hejnova J, et al.
Effect of aerobic training on plasma levels and subcutaneous abdominal adipose tissue gene expression of adiponectin, leptin, interleukin 6, and tumor necrosis factor alpha in obese women. Metabolism 2006;55:1375-81.
[35] Esposito K, Pontillo A, Di Palo C, Giugliano G, Masella M, Marfella R, et al. Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women: a randomized trial. JAMA 2003;289:1799-804.
[36] Ryan AS, Nicklas BJ, Berman DM, Elahi D. Adiponectin levels do not change with moderate dietary induced weight loss and exercise in obese postmenopausal women. Int J Obes Relat Metab Disord 2003;
27:1066-71.
[37] Nicklas BJ, You T, Pahor M. Behavioral treatments for chronic systemic inflammation: effects of dietary weight loss and exercise training. CMAJ 2005;172:1199-209.
[38] Niswender K. Diabetes and obesity: therapeutic targeting and risk reduction—a complex interplay. Diabetes Obes Metab 2010;12:267-87.