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Comparison of the effects of cow’s milk, fortified soy milk, and calcium supplement on plasma adipocytokines in overweight or obese women



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Please cite this paper as:
Faghih s, Hedayati M, Abadi A, Kimiagar SM. Comparison of the effects of cow’s milk, fortified soy milk, and calcium supplement on
plasma adipocytokines in overweight or obese women. Int J Endocriol Metab. 2010; 8(4):188-93.
Comparison of the effects of cow’s milk, fortified soy milk, and calcium
supplement on plasma adipocytokines in overweight or obese women
Shiva Faghih ¹*, Mehdi Hedayati ², Alireza Abadi ³, Seyed Masoud Kimiagar 4
1 Department of Nutrition, School of Health and Nutrition, Shiraz University of Medical Sciences, shiraz, IR Iran
2 Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran
3 Department of Statistics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran
4 Department of clinical nutrition, Faculty of Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran
Copyright c 2010, Iran Endocrine Society, Published by Kowsar M.P.Co. All rights reserved.
* Corresponding author at: Shiva Faghih, Department of Nutrition,
School of Health and Nutrition, Shiraz University of Medical Sciences,
Razi Blvd, Shiraz, IR Iran. Tel:+9126305829
Implication for health policy/practice/research/medical education:
Obesity and its complications are the major concerns of health care practitioners, and finding proper diet to reduce this problem is
critical. Results of this article are useful for nutritionists, epidemiologists and physicians.
Background: Obesity is an escalating public health problem. Adipose tissue synthesizes
and secretes a variety of biological molecules, termed adipcytokines, that may contrib-
ute to obesity-linked metabolic abnormalities including cardiovascular diseases.
Objectives: We compared the effects of cowʹs milk, calcium-fortified soy milk, and
a calcium supplement on adipo cytokines in premenopausal overweight and obese
Materials and Methods: In this clinical trial, 100 healthy, overweight or obese premeno-
pausal women were randomly assigned to one of the following dietary regimens for 8
weeks: (a) a control diet (b), a calcium-supplemented diet containing 800 mg/day cal-
cium carbonate, (c) a high-milk diet containing three servings of low-fat milk, and (d) a
soy-milk diet containing three servings of calcium-fortified soy milk. All diets required
a 500-kcal/day reduction in energy. At baseline and after 8 weeks, anthropometric indi-
ces and plasma leptin, adiponectin, TNFα, CRP, and IL-6 were measured.
Results: Plasma CRP and leptin were significantly correlated with all anthropometric
indices except for WHR, and plasma adiponectin had a significant negative correlation
with WHR at baseline. Plasma leptin, CRP, and IL-6 decreased significantly in all groups
(P < 0.01; except for CRP in the control group), but there were no significant differences
among the four groups for these three measures.
Conclusions: We conclude that a dietary reduction of 500-kcal/day has beneficial effects
on plasma adipocytokines, but calcium intake either as calcium carbonate or as milk
leads to no differences. These results merit further research.
Article history:
Received: 13 May 2010
Revised: 10 Jun 2010
Accepted: 1 Jan 2011
Article Type:
Original Article
c 2010 Kowsar M.P.Co. All rights reserved.
1. Background
Obesity is an escalating public health problem (1-4) De-
fined as the accumulation of excess body fat (5, 6). obe-
sity is a principle causative factor in the development of
metabolic disorders such as insulin resistance, hyperten-
sion, hyperglycemia, dyslipidemia, and atherosclerosis
(6, 7). Adipose tissue is currently considered to be a hor-
monally active system in the control of metabolism and
not only as a store of excess energy (5, 8, 9). It synthesizes
and secretes a variety of biological molecules, including
Int J Endocrinol Metab. 2010;8(4):188-193
Cow’s milk, soy milk, and calcium and plasma adipocytokines Faghih S et al.
adiponectin, leptin, tumor necrosis factor alpha (TNFα),
and interlukin-6 (IL-6) (5, 9-11). Recent research has re-
vealed that substances such as C-reactive protein (CRP),
IL-6, and TNFα mirror oxidative stress and may play a role
in promoting adverse vascular outcomes in metabolic
syndrome and type 2 diabetes (12, 13). TNFα is overex-
pressed in white adipose tissue in obesity and decreases
with weight loss and improvement of insulin sensitiv-
ity (14). Subsequent studies have demonstrated that CRP
concentrations are significantly related to various mea-
sures of body fat, and weight loss may lead to a decrease
in CRP concentration (15, 16).
Leptin is a hormone primarily secreted by the adipose
tissue and represents several physiological functions
(17). Although the principal effects of leptin in the central
nervous system are the control of food intake and energy
expenditure, there is a significant relationship between
leptinaemia and the chronic subinflammatory state that
accompanies obesity which suggests that other possible
peripheral biological effects are associated with its cyto-
kine-like structure (18).
In sharp contrast to most adipokines, adiponectin ex-
pression and serum concentrations do not increase and
actually decrease in a variety of obese and insulin-resis-
tant states (14). Adiponectin is produced in fat cells (19),
and in addition to its effects on insulin sensitivity, it has
anti atherogenic properties (14, 18).
Various studies have demonstrated that weight loss
results in significant increases in serum levels of adipo-
nectin and significant reduction in plasma CRP (20, 21).
Sun and Zemel’s findings indicated that dietary calcium
suppresses obesity-associated inflammatory status by
modulating proinflammatory and anti-inflammatory
factor expression in mice (22). A few studies have specifi-
cally focused on the effects of calcium or dairy consump-
tion on plasma adipocytokines (16, 22-25). One of these
studies was conducted on mice (22), and 2 of them evalu-
ated the effect of calcium on CRP (16, 23). In the present
study, we examined the effects of cowʹs milk, fortified soy
milk, and calcium supplement on serum adipocytokines
in overweight or obese women.
3. Material and Methods
3.1 Study sample
Using an effect size of 0.55 for our sample size equa-
tions, 20 people for each group were estimated. Then we
added 25% to this number, so 25 people for each group
were included in the analyses. One hundred healthy, pre-
menopausal, overweight or obese women ranging in age
from 20 to 50 years volunteered to participate in this ran-
domized clinical trial, and 85 completed the study. Fif-
teen subjects dropped out for various reasons, including
thyroid disease, not wanting or being able to consume
soy milk or a calcium supplement, and choosing not to
continue participation. There were no significant differ-
ences between those who completed the study and those
who did not for any of the main variables. Inclusion crite-
ria were as follows: body mass index (BMI) more than 25
kg/m²; taking no medications or supplements that might
affect metabolism of calcium, vitamin D, or weight loss;
absence of menopause; stable body weight (body weight
changed less than 3kg for the last 2 months); and absence
of diabetes, hypertension, coronary-artery, thyroid, and
kidney diseases. The subjects were nonpregnant and non-
lactating with no allergy to milk or soy milk and lactose
intolerance. We also made sure that the subjects had not
participated in any other studies in the 6 months preced-
ing the screening. The study was approved by the ethics
committee of the National Nutrition and Food Technol-
ogy Research Institute. Each potential participant was in-
formed of the possible risks and benefits associated with
this study and provided written signed consent.
3.2 Study interventions
For the first 2 weeks of the study, we collected the sub-
jects’ baseline dietary data and physical activity assess-
ments. Then, we randomized the subjects to one of the
following dietary regimens for 8 weeks:
1. A control diet that required a 500-kcal/day reduction
in total intake (based on the Harris-Benedict equa-
tion), with 500 to 600 mg/day of dietary calcium
(about 1.5 to 2 servings of dairy products);
2. A calcium-supplemented diet identical to the control
diet except for the addition of 800 mg/day of calcium
( as calcium carbonate);
3. A milk diet that required a 500 kcal/day reduction in
total intake and containing three servings (220 ml
each) of low fat milk (1.5%); and
4. A soy-milk diet that required a 500-kcal/day reduc-
tion in total intake and three servings of calcium
fortified soy milk per day. The total calcium intake
for the milk diet and the soy-milk diet were between
1,200 and 1,300 mg/day.
Daily caloric requirements for all diets were calculated
by using the Harris-Benedict equation (15). After adjust-
ing the caloric intakes for each participant’s physical
activity level, individualized meal plans were given to
each participant based on a 500 kcal/day reduction from
their estimated caloric requirements (26). The diets for
all groups were designed to provide comparable levels
of macro nutrients as follows: 55% carbohydrate, 18%
protein, and 27% fat. At baseline and at 2-week intervals,
weight, waist circumference, and hip circumference
were measured, and 24-hr dietary records (27) as well as
physical-activity records (2 weekdays and 1 weekend day)
were taken. Body fat was measured at the beginning of
the study and at Week 8 using a Bodystat bioelectric im-
pedance analysis (Quadscan4000 model).
At baseline and after 8 weeks, fasting blood samples
(10 ml) were obtained in the morning. The plasma
was separated and frozen at -80ºC for later analy-
Int J Endocrinol Metab. 2010;8(4):188-193
190 Cow’s milk, soy milk, and calcium and plasma adipocytokines
Faghih S et al.
sis. Adiponectin (Mercodia, Uppsala, Sweden), leptin
(Mercodia,Uppsala,Sweden), TNFα (Diaclon, France), IL-6
(Diaclon, Besancon, France), and CRP (Diagnostics Bio-
chem Canada) were measured using a sandwich Elisa
3.3 Statistical analysis
Dietary records were analyzed using Nutritionist 4 (N
IV). Statistical analyses were performed with SPSS soft-
ware, version 15. One-way ANOVAs were used to compare
the characteristics of the subjects in the four groups at
baseline and also to compare the mean differences of
plasma adipocytokines among the four groups. The ef-
fect of the intervention in each group was tested using
paired-samples t-tests, and the relationships between
plasma adipocytokines and anthropometric indices
were estimated using Pearson correlations. P < 0.05 was
considered significant.
4. Results
Of the 100 women meeting the general eligibility cri-
teria, 15 dropped out before completing the weight-loss
period (5, 3, 3, and 4 persons in control, calcium supple-
ment, high milk, and soy milk groups respectively). Plas-
ma CRP, IL-6, and TNFα were not normally distributed, so
we used logs of them in the analysis.
The baseline characteristics of subjects are shown in
Table 1. It is apparent that there were no significant dif-
ferences between the age, weight, BMI, or energy and
calcium intake of subjects across the four groups.
The relationship among plasma adipocytokines and an-
thropometric indices at baseline are shown in Table 2. It
is clear that plasma CRP and leptin were significantly cor-
related with all anthropometric indices except for waist
to hip ratio WHR, that plasma adiponectin had a signifi-
cant negative correlation with WHR, and that there were
no significant correlations among TNFα and IL-6 and the
anthropometric indices.
Table 3 shows that after 8 weeks, the correlations among
plasma adipocytokines and anthropometric indices were
the same as they were at baseline, except for plasma
leptin, which showed no significant correlation. The an-
thropometric indices of all groups decreased significant-
ly after 8 weeks of weight-loss intervention (P < 0.001for
all), but the amount of these reductions was significantly
different among the four groups for only waist circum-
ference (P = 0.029) and WHR (P = 0.015). After adjusting
for baseline values with analyses of covariance, however,
changes in weight and BMI were significantly different
among the four groups (P = 0.017 and P = 0.019, respec-
tively). Post hoc tests showed that the changes in waist
circumference and WHR were significantly higher in the
high-milk (6.32 ± 2.50 cm and 0.048 ± 0.019) and soy-milk
(5.84 ± 1.47 cm and 0.044 ± 0.019) groups than in the con-
trol group (3.98 ± 2.77 cm and 0.021 ± 0.016; P < 0.01 and
P < 0.05, respectively). Also, the reductions in weight and
BMI were significantly greater in the high-milk group
(4.43 ± 1.93 kg and 1.74 ± 0.73 kg/m²) than in the control
group (2.87 ± 1.55 kg and 1.15 ± 0.62 kg/m²; P < 0.01for all).
Variables Control
(n = 20)
Ca supplement
(n = 22)
High milk
(n = 22)
Soy milk
(n = 21)
P b
Age, y38.25 ± 9.49 a35.77 ± 8.70 38.27 ± 10.43 37.54 ± 9.27 0.78
Weight, kg 76.78 ± 9.6 78.16 ± 11.43 76.24 ± 10.57 80.05 ± 13.32 0.69
BMI, kg/m² 30.78 ± 3.13 31.54 ± 4.12 30.01 ± 3.55 31.09 ± 4.13 0.58
Energy, kcal/d 1839 ± 169 1870 ± 201 1937 ± 177 1901 ± 148 0.32
Calcium, mg/d 512 ± 172 532 ± 149 484 ± 131 509± 101 0.73
a mean ± SD
b One way ANOVA
Table 1. Baseline characteristics of subjects under study
a NS = not significant
Table 2. Correlation of plasma adipocytokines and anthropometric indices at baseline
Weight, kg Waist circumference, cm BMI, kg/m² Body fat mass (%) WHR
CRP, ng/ml r = 0.34
p = 0. 001
r = 0.41
p = 0. 0001
r = 0.42
p = 0. 0001
r = 0.41
p = 0. 0001
TNFα, pg/ml NS aNS NS NS NS
IL-6, pg/ml
Leptin, ng/ml r = 0.49
p = 0. 0001
r = 0.52
p = 0. 0001
r = 0.56
p = 0. 0001
r = 0.47
p = 0. 0001
Adiponectin, ng/ml NS NS NS NS r = - 0.27
p = 0. 013
Int J Endocrinol Metab. 2010;8(4):188-193
Cow’s milk, soy milk, and calcium and plasma adipocytokines Faghih S et al.
a NS = not significant
Anthropometric indices
Weight, kg Waist circumference, cm BMI, kg/m² Body fat mass (%) WHR
CRP, ng/ml r = 0.31
p = 0.003
r = 0.37
p = 0.0001
r = 0.41
p = 0.0001
r = 0.40
p = 0.0001
r = 0.24
TNFα, pg/ml NS aNS NS NS NS
IL-6, pg/ml
Leptin, ng/ml NS NS NS NS NS
Adiponectin, ng/ml NS NS NS NS r = - 0.23
p = 0.03
Table 3. Correlation of plasma adipocytokines and anthropometric indices after intervention
The data in Table 4 indicate that plasma IL-6 and leptin
decreased significantly in all four groups, but there were
no significant reduction in plasma TNFα or adiponectin.
The reduction of plasma CRP was significant in the three
experimental groups but not the control group. Mean
differences of plasma adipocytokines among the four
groups were not significant.
5. Discussion
Results of this study showed that plasma CRP and
leptin were significantly correlated with body weight,
waist circumference, body fat, and BMI. Inflammatory
markers, such as CRP and IL-6, are higher in obese indi-
viduals than in lean subjects (12). The insulin resistance
and atherosclerosis study showed that CRP values corre-
lated with BMI, waist circumference, and fasting hyper-
insulinemia (13). There are several studies that indicate
that serum leptin concentration is proportional to body-
fat mass (17, 28, 29).
Additionally, in this study there was a significant cor-
relation between plasma adiponectin and WHR. It seems
a All values are Mean ± SD
b No significant differences were seen among groups (One way ANOVA)
c Significant difference between before and after P < 0.001
d Significant difference between before and after P < 0.01
e Significant difference between before and after P < 0.05
Variables aGroups b Time Changes
Before After
TNFα, pg/ml Control (19)
Ca supplement (21)
low fat milk (21)
Soy milk (20)
6.60 ± 4.57
6.48 ± 1.94
8.30 ± 6.72
4.96 ± 2.51
6.26 ± 4.17
5.91 ± 1.78
7.91 ± 5.91
4.94 ± 2.84
-0.34 ± 0.44
-0.82 ±0.26
-0.38 ± 0.50
-0.12 ± 0.40
CRP, ng/ml Control (19)
Ca supplement (21)
low fat milk (21)
Soy milk (20)
2.92 ± 1.99
2.60 ± 2.24
1.92 ± 2.06
3.29 ± 2.35
2.60 ± 2.63
2.05 ± 1.88
1.17 ± 1.32
2.27 ± 2.11
-0.31 ± .043
0.54 ± 0.26 e
0.75 ± 0.19 c
0.97 ± 0.38 e
IL-6, pg/ml Control (19)
Ca supplement (21)
low fat milk (21)
Soy milk (20)
1.56 ± 1.20
1.54 ± 0.64
1.18 ± 0.57
1.02 ± 0.48
1.15 ± 0.86
1.03 ± 0.51
0.89 ± 0.37
0.76 ± 0.42
-0.40 ± 0.11 d
-0.55 ± 0.11 d
-0.29 ± 0.08 c
-0.24 ± 0.10 d
leptin, ng/ml Control (19)
Ca supplement (21)
low fat milk (21)
Soy milk (20)
21.54 ± 9.42
21.96 ± 8.65
20.37 ± 12.3
20.75 ± 9.85
14.88 ± 7.56
18.56 ± 9.31
11.75 ± 9.05
14.29 ± 5.85
-6.65 ± 1.40 c
-5.10 ± 1.22 e
-8.61 ± 1.27 c
-5.78 ± 1.68 d
Adiponektin, ng/ml Control (19)
Ca supplement (21)
low fat milk (21)
Soy milk (20)
8.37 ± 1.99
8.61 ± 2.69
10.32 ± 3.65
8.33 ± 2.62
7.96 ± 2.55
8.36 ± 2.04
10.08 ± 3.41
7. ± 2.1063
-0.40 ± 0.61
-0.55 ± 0.46
-0.24 ± 0.56
-0.53 ± 0.31
Table 4. Within and between groups comparison of the effects of 8-week weight-loss intervention on plasma adipocytokines
Int J Endocrinol Metab. 2010;8(4):188-193
192 Cow’s milk, soy milk, and calcium and plasma adipocytokines
Faghih S et al.
that visceral obesity is predominantly associated with
reduced levels of adiponectin; obese women who have
normal upper-body fat have normal adiponectin levels
as well (13).
In this study, a dietary reduction of 500 kcal/day for
8 weeks led to significant decreases in plasma IL-6 and
leptin and no significant changes in plasma TNFα in any
group. Plasma CRP decreased significantly in all three
experimental groups but not the control group. Leptin
is related to the risk of diabetes (30) and cardiovascular
disease (31) in the elderly. It has been reported that an
imposed energy deficit causes decreases in circulating
leptin (29, 32). Copolla et al. reported that after 12 months
of a multidisciplinary program of weight reduction,
obese women lost at least 10% of their original weight,
and their CRP levels decreased significantly (P < 0.01)
(20). Additionally, Madsen et al. showed that weight loss
was associated with a significant decrease in CRP (21). Sun
and Zemel found that a high-calcium diet significantly
inhibited the expression of TNFα and IL-6 and stimulated
the expression of adiponectin in visceral fat (P < 0.001)
in male aP2-agoti transgenic mice (6). They also found
similar effects in a retrospective analysis of archival clini-
cal samples from obese subjects, with high dairy intake
reducing CRP and increasing adiponectin under both
eucaloric and hypocaloric conditions. Sun and Zemel
suggested that although the reduction of CRP levels was
independent of changes in body weight, it is not possible
to fully ignore the effect of reduced adiposity, as subjects
exhibited reduced body fat. Circulating 1α, 25-dihydroxy-
cholecalciferol was reduced with increased Ca intake,
concurrent with reductions in pro-inflammatory indi-
ces, suggesting a role for dietary Ca in attenuating the
cytokine dysregulation related to diet-induced obesity
(25). Also, research has suggested that parathyroid hor-
mone regulates the circulating levels of the inflamma-
tory cytokines interleukin-6 and tumor necrosis factor-α,
which in turn stimulate production of CRP and calcium
supplementation, by suppressing parathyroid hormone
production, might also decrease serum CRP (23).
In contrast, Pittas et al. found that daily consumption of
either 500 mg of calcium citrate and 700 IU of vitamin D
or placebo for 3 years had no significant effects on plas-
ma IL-6 and CRP (26). Also Grey et al. reported that after 1
year of calcium supplementation (1g calcium citrate per
day), there was no difference between the CRP levels of
the supplement and placebo groups (25).
Despite the 5-cm reduction in waist circumference and
approximately 5% reduction in body weight, there was no
significant change in plasma adiponectin in this study.
Maestu et al. reported that after a 10-week intervention,
no change in adiponectin concentration was observed,
despite significant weight and fat mass loss (6.5% reduc-
tion) in male competitive bodybuilders (17). Xydakis et
al. observed no change in plasma adiponectin after 4 to
6 weeks of weight loss (11). On the other hand, Madsen
et al. found that a mean weight loss of about 12% after 8
weeks of VLCD resulted in a significant 22% increase in se-
rum levels of adiponectin. They also found that relatively
large weight losses (more that 10-11%) were necessary to
obtain a significant increase in plasma adiponectin lev-
els (21).
Despite the reductions in waist circumference, WHR,
body weight, and BMI were significantly different across
all four groups, but plasma adipocytokine changes were
not significantly different in any group. We assume that,
although the reductions in anthropometric indices were
significantly different among the four groups, they were
not high enough to exert different effects on the subjects’
adipocytokines expressions.
For this study, we conclude that calcium intake as cal-
cium carbonate, calcium-fortified soy milk, or low-fat
milk leads to no differences in plasma adipocytokines.
Still, given the short duration of this study, future studies
with longer experimental periods are warranted.
Financial support
This article was funded by Institute of Nutrition and
Food Technology, Shahid Beheshti University of Medical
Conflict of interest
There is no conflict of interest.
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Obesity predisposes individuals to congestive heart failure (CHF) and cardiovascular disease (CVD). Leptin regulates energy homeostasis, is elevated in obesity, and influences ventricular and vascular remodeling. We tested the hypothesis that leptin levels are associated with greater risk of CHF, CVD, and mortality in elderly individuals. We evaluated 818 elderly (mean age 79 years, 62% women) Framingham Study participants attending a routine examination at which plasma leptin was assayed. Leptin levels were higher in women and strongly correlated with BMI (P < 0.0001). On follow-up (mean 8.0 years), 129 (of 775 free of CHF) participants developed CHF, 187 (of 532 free of CVD) experienced a first CVD event, and 391 individuals died. In multivariable Cox regression models adjusting for established risk factors, log-leptin was positively associated with incidence of CHF and CVD (hazard ratio [HR] per SD increment 1.26 [95% CI 1.03-1.55] and 1.28 [1.09-1.50], respectively). Additional adjustment for BMI nullified the association with CHF (0.97 [0.75-1.24]) but only modestly attenuated the relation to CVD incidence (1.23 [1.00-1.51], P = 0.052). We observed a nonlinear, U-shaped relation between log-leptin and mortality (P = 0.005 for quadratic term) with greater risk of death evident at both low and high leptin levels. In our moderate-sized community-based elderly sample, higher circulating leptin levels were associated with a greater risk of CHF and CVD, but leptin did not provide incremental prognostic information beyond BMI. Additional investigations are warranted to elucidate the U-shaped relation of leptin to mortality.
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To clarify the association of circulating levels of leptin with risk for cardiovascular disease (CVD) events and new-onset diabetes in men and women. We related baseline leptin levels to CVD events (n = 864) and incident diabetes (n = 289) in an elderly population (n = 5,672) over 3.2 years of follow-up. In treatment-, age-, and country-adjusted models, leptin was not associated with risk of CVD in men (hazard ratio 1.02 [95% CI 0.90-1.16] per unit log-leptin increase) or women (1.05 [0.91-1.20]) but was associated with risk of diabetes in men (2.75 [2.14-3.52]) and women (1.54 [1.22-1.94]). After adjusting for classic risk factors and BMI, C-reactive protein, and glucose, the diabetes association retained significance in men (1.85 [1.30-2.63]) but not in women (0.89 [0.64-1.26]). Leptin, similar to other markers of adiposity in general, is more strongly related to risk of diabetes than CVD in the elderly.
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Adiponectin, also called GBP-28, apM1, AdipoQ and Acrp30, is a novel adipose tIssue-specific protein that has structural homology to collagen VIII and X and complement factor C1q, and that circulates in human plasma at high levels. It is one of the physiologically active polypeptides secreted by adipose tIssue, whose multiple functions have started to be understood in the last few Years.A reduction in adiponectin expression is associated with insulin resistance in some animal models. Administration of adiponectin has been accompanied by a reduction in plasma glucose and an increase in insulin sensitivity. In addition, thiazolidinediones, drugs that enhance insulin sensitivity through stimulation of the peroxisome proliferator-activated receptor-gamma, increase plasma adiponectin and mRNA levels in mice. On the other hand, this adipocyte protein seems to play a protective role in experimental models of vascular injury. In humans, adiponectin levels are inversely related to the degree of adiposity and positively associated with insulin sensitivity both in healthy subjects and in diabetic patients. Plasma adiponectin levels have been reported to be decreased in some insulin-resistant states, such as obesity and type 2 diabetes mellitus, and also in patients with coronary artery disease. On the contrary, chronic renal failure, type 1 diabetes and anorexia nervosa are associated with increased plasma adiponectin levels. Concentrations of plasma adiponectin have been shown to correlate negatively with glucose, insulin, triglyceride levels and body mass index, and positively with high-density lipoprotein-cholesterol levels and insulin-stimulated glucose disposal. Weight loss and therapy with thiazolidinediones increased endogenous adiponectin production in humans. Adiponectin increases insulin sensitivity by increasing tIssue fat oxidation, resulting in reduced circulating fatty acid levels and reduced intracellular triglyceride contents in liver and muscle. This protein also suppresses the expression of adhesion molecules in vascular endothelial cells and cytokine production from macrophages, thus inhibiting the inflammatory processes that occur during the early phases of atherosclerosis. In view of these data, it is possible that hypoadiponectinemia may play a role in the development of atherosclerotic vascular disease. In summary, the ability of adiponectin to increase insulin sensitivity in conjunction with its anti-inflammatory and anti-atherogenic properties have made this novel adipocytokine a promising therapeutic tool for the future, with potential applications in states associated with low plasma adiponectin levels.
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The purpose of this study was to determine changes in adiponectin levels with moderate weight loss, weight loss plus aerobic exercise, or weight loss plus resistive exercise in overweight and obese, sedentary postmenopausal women. Longitudinal, clinical intervention study of 6-month (3 x /week) program of either weight loss (WL, n=15), weight loss + aerobic exercise (WL+AEX, n=16), or weight loss + resistive exercise (WL+RT, n=9) We studied 40 sedentary, overweight and obese (body mass index, BMI=32+/-1 kg/m(2), X+/-s.e.m.) postmenopausal (57+/-1y) women. Fat mass and fat-free mass (FFM) by dual-energy X-ray absorptiometry, plasma insulin, leptin, and adiponectin by radioimmunoassay. Age, body weight, BMI, waist and hip circumferences, waist-to-hip ratio, VO(2)max, percent fat, total body fat mass, FFM, and fasting plasma glucose, insulin, leptin, and adiponectin concentrations were similar among WL, WL+AEX, and WL+RT groups before the interventions. In all women combined, body weight, BMI, and waist and hip circumferences decreased (P < 0.001). There was a significant absolute decrease in percent body fat from 47 to 44%, representing a 13% decrease in total fat mass and a -1.6% change in FFM. Fasting concentrations of plasma adiponectin did not change (40+/-16%, P=NS), whereas fasting plasma glucose, insulin, and leptin all decreased (P<0.001). Plasma adiponectin levels do not change with a 6-month moderate weight reduction program even when accompanied by aerobic or resistive exercise training in overweight and obese postmenopausal women.
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Increasing 1,25-dihydroxyvitamin D in response to low-calcium diets stimulates adipocyte Ca2+ influx and, as a consequence, stimulates lipogenesis, suppresses lipolysis, and increases lipid accumulation, whereas increasing dietary calcium inhibits these effects and markedly accelerates fat loss in mice subjected to caloric restriction. Our objective was to determine the effects of increasing dietary calcium in the face of caloric restriction in humans. We performed a randomized, placebo-controlled trial in 32 obese adults. Patients were maintained for 24 weeks on balanced deficit diets (500 kcal/d deficit) and randomized to a standard diet (400 to 500 mg of dietary calcium/d supplemented with placebo), a high-calcium diet (standard diet supplemented with 800 mg of calcium/d), or high-dairy diet (1200 to 1300 mg of dietary calcium/d supplemented with placebo). Patients assigned to the standard diet lost 6.4 +/- 2.5% of their body weight, which was increased by 26% (to 8.6 +/- 1.1%) on the high-calcium diet and 70% (to 10.9 +/- 1.6% of body weight) on the high-dairy diet (p < 0.01). Fat loss was similarly augmented by the high-calcium and high-dairy diets, by 38% and 64%, respectively (p < 0.01). Moreover, fat loss from the trunk region represented 19.0 +/- 7.9% of total fat loss on the low-calcium diet, and this fraction was increased to 50.1 +/- 6.4% and 66.2 +/- 3.0% on the high-calcium and high-dairy diets, respectively (p < 0.001). Increasing dietary calcium significantly augmented weight and fat loss secondary to caloric restriction and increased the percentage of fat lost from the trunk region, whereas dairy products exerted a substantially greater effect.
Obesity which is defined as accumulation of excess body fat, is a major cause of atherosclerotic vascular disease in industrial countries. Recent advances in the biology of adipose tissue have revealed that adipose tissue is not simply an energy storage organ but it also secretes a variety of molecules which affect the metabolism of the whole body. Through a systematic search of active genes in adipose tissue, we found that adipose tissue, especially visceral fat expressed numerous genes for secretory proteins (about 30% of total genes analyzed). Among them, plasminogen activator-1 (PAI-1), which is a regulator of the fibrinolytic system, was overexpressed in the visceral fat in an animal model of obesity. Plasma levels of PAI-1 were closely correlated with visceral fat adiposity. Thus, PAI-1 secreted from visceral fat may play some role in thrombotic vascular disease in visceral obesity. Adiponectin, a novel adipose-specific gene product, which has a matrix-like structure, is abundantly present in the bloodstream. Dysregulated secretion of adiponectin may be related to vascular disease in obesity. Biologically active molecules secreted from adipose tissue (adipocytokines) may have important roles in the development of atherosclerotic disease in obesity.
Obesity is a growing epidemic with subsequent health consequences leading not only to reduced quality of life but also to increased medical costs. Growing evidence supports a relationship between increased calcium intakes and reductions in body weight specific to fat mass. Since the first observations in rats >10 y ago, several recently published clinical studies support this relationship as well. The impact of calcium intake on weight loss or prevention of weight gain has been demonstrated in a wide age range of Caucasian and African-Americans of both genders. This review focuses on the results of clinical trials that have investigated the impact of calcium and dairy products on prevention of weight gain, weight loss or development of the insulin resistance syndrome. The implications of these results are that calcium may play a substantial contributing role in reducing the incidence of obesity and prevalence of the insulin resistance syndrome.
Adiponectin is an adipocyte-derived plasma protein that accumulates in the injured artery and has potential antiatherogenic properties. This study was designed to determine whether a decreased plasma adiponectin level (hypoadiponectinemia) can be independently associated with the prevalence of coronary artery disease (CAD). The consecutive 225 male patients were enrolled from inpatients who underwent coronary angiography. Voluntary blood donors (n=225) matched for age served as controls. Plasma adiponectin levels in the CAD patients were significantly lower than those in the control subjects. Multiple logistic regression analysis including plasma adiponectin level, diabetes mellitus, dyslipidemia, hypertension, smoking habits, and body mass index revealed that hypoadiponectinemia was significantly and independently correlated with CAD (P<0.0088). The entire study population was categorized in quartiles based on the distribution of plasma adiponectin levels. The interquartile cutoff points were 4.0, 5.5, and 7.0 microg/mL. The multivariate-adjusted odds ratios for CAD in the first, second, and third quartiles were 2.051 (95% confidence interval [CI], 1.288 to 4.951), 1.221 (95% CI, 0.684 to 2.186), and 0.749 (95%CI, 0.392 to 1.418), respectively. Male patients with hypoadiponectinemia (<4.0 microg/mL) had a significant 2-fold increase in CAD prevalence, independent of well-known CAD risk factors.
Loss of body fat by caloric restriction is accompanied by decreased circulating leptin levels, increased ghrelin levels, and increased appetite. In contrast, dietary fat restriction often decreases adiposity without increasing appetite. Substitution of dietary carbohydrate for fat has been shown to increase the area under the plasma leptin vs. time curve (AUC) over the course of 24 h. This effect, if sustained, could explain the absence of a compensatory increase in appetite on a low fat diet. To clarify the effect of dietary fat restriction on leptin and ghrelin, we measured AUC for these hormones in human subjects after each of the following sequential diets: 2 wk on a weight-maintaining 35% fat (F), 45% carbohydrate (C), 20% protein (P) diet (n = 18); 2 wk on an isocaloric 15% F, 65% C, 20% P diet (n = 18); and 12 wk on an ad libitum 15% F, 65% C, 20% P diet (n = 16). AUC for leptin was similar on the isocaloric 15% F and 35% F diets (555 +/- 57 vs. 580 +/- 56 ng/ml.24 h; P = NS). Body weight decreased from 74.6 +/- 2.4 to 70.8 +/- 2.7 kg on the ad libitum 15% F diet (P < 0.001) without compensatory increases in food consumption or AUC for ghrelin. Proportional amplitude of the 24-h leptin profile was increased after 12 wk on the 15% fat diet. We conclude that weight loss early in the course of dietary fat restriction occurs independently of increased plasma leptin levels, but that a later increase in amplitude of the 24-h leptin signal may contribute to ongoing weight loss. Fat restriction avoids the increase in ghrelin levels caused by dietary energy restriction.
It is now recognized that the white adipose tIssue (WAT) produces a variety of bioactive peptIdes, collectively termed "adipokines". Alteration of WAT mass in obesity or lipoatrophy, affects the production of most adipose secreted factors. Since both conditions are associated with multiple metabolic disorders and increased risk of cardiovascular diseases, the Idea has emerged that WAT could be instrumental in these complications, by virtue of its secreted factors. Several adipokines are increased in the obese state and have been implicated in hypertension (angiotensinogen), impaired fibrinolysis (PAI-1) and insulin resistance (ASP, TNFalpha, IL-6, resistin). Conversely, leptin and adiponectin both exert an insulin-sensitizing effect, at least in part, by favoring tIssue fatty-acId oxIdation through activation of AMP-activated kinase. In obesity, insulin resistance has been linked to leptin resistance and decreased plasma adiponectin. In lipoatrophic mice, where leptin and adiponectin circulating levels are low, administration of the two adipokines synergistically reverses insulin resistance. Leptin and adiponectin also have distinct properties: leptin, as a long-term integrative signal of energy store and adiponectin, as a potent anti-atherogenic agent. The thiazolIdinedione anti-diabetic drugs increase endogenous adiponectin production in rodents and humans, supporting the Idea that the development of new drugs targeting adipokines might represent a promising therapeutic approach to protect obese patients from insulin resistance and atherosclerosis.