Assessment of serum chemerin level in an
Iranian population with metabolic syndrome and healthy individuals in 2016
Zanganeh
Sh, BSc1, Roostaei F, BSc1, Shafiepour MR, PhD2,
Mahmoodi M, PhD3, Khoshdel A, PhD4, Hajizadeh MR, PhD4
⃰
1-
MSc Student of Clinical Biochemistry, Dept. of Clinical Biochemistry, Faculty
of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran. 2-
Assistant Prof., of Internal medicine, Dept. of Faculty of Medicine, Rafsanjan
University of Medical Sciences, Rafsanjan, Iran. 3-Prof., of Clinical
Biochemistry, Molecular Medicine Research Center and Dept. of Clinical
Biochemistry, Faculty of Medicine, Rafsanjan University of Medical Sciences,
Rafsanjan, Iran. 4- Assistant Prof., of Clinical Biochemistry, Molecular
Medicine Research Center and Dept. of Clinical Biochemistry, Faculty of
Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
Abstract
Received:
June
2016, Accepted:
October 2016
Background: Chemerin is and adipokine
produced and secreted by adipose tissue and is associated with functions such
as insulin resistance, inflammation, and blood pressure regulation. The
purpose of the present study was the determination of serum chemerin level in
an Iranian population with metabolic syndrome and its comparison with healthy
individuals. Materials
and Methods: The
study subjects consisted of 31 individuals with metabolic syndrome and 25
healthy individuals (control group). Serum chemerin level was measured and
its relationship with indices of metabolic syndrome, obesity, and insulin
resistance was determined. The collected data were analyzed using independent
two-sample t-test and the Pearson correlation coefficient in SPSS software. Results: Serum chemerin level was
significantly higher in the metabolic syndrome group compared to the control
group (P = 0.009). The mean of the measured indices of BMI (P < 0.001),
waist circumference (P < 0.001), systolic blood pressure (P = 0.001),
diastolic blood pressure (P < 0.001), insulin resistance (P = 0.001), and
triglyceride (P < 0.001) was significantly higher in the metabolic
syndrome group compared to the control group. However, HDL level was significantly
higher in the control group compared to the metabolic syndrome group (P =
0.007). Conclusions: Serum chemerin level was
higher among patients with metabolic syndrome compared to healthy
individuals. Thus, it can be concluded that serum chemerin level measurement
can be effective in the diagnosis of this syndrome and determination of
appropriate treatment methods. |
Keywords: Chemerin, Obesity, Insulin
Resistance, Metabolic Syndrome
Introduction
Today, obesity, as
one of the consequences of the modern lifestyle (increased food intake and a sedentary
lifestyle), has become an international concern (1). Inflammation caused by
adipose tissue, which increases with obesity, increases the risk of incidence
of many diseases such as fatty liver and metabolic syndrome (2). Metabolic
syndrome consists of a series of metabolic abnormalities such as central
obesity, insulin resistance, hyperglycemia, hypertension, and dyslipidemia
which increase the risk of diabetes and cardiovascular diseases (CVD) (3, 4).
Regardless of the difference in the prevalence of this disease in different
areas due to factors such* as race and
climate, it has been reported that one-fourth of the world population suffer
from metabolic syndrome (5, 6). According to the World Health Organization
(WHO) reports, metabolic syndrome is the new pandemic of the 21st
century and it is anticipated that approximately half of the world population
will be suffering from this disease in the span of the next 20 years. In Iran,
the incidence of this disease has had an increasing trend; its prevalence increased
from 30.1% in 2002 to 34.7% in 2009 (7).
Adipokines (e.g.,
Leptin, adiponectin, and chemerin) are polypeptide produced and secreted by
adipose tissue and are associated with functions such as insulin resistance,
inflammation, and blood pressure regulation (7, 8). Chemerin, also known as
tazarotene-induced gene 2 protein (TIG2) and retinoic acid receptor responder
protein 2 (RARRES2), is an adipokine. This adipokine plays a role in different
functions through adipocyte and immune cell surface receptors. Chemerin acts as
a chemotactic factor, and using its receptors on the surface of immune cells,
causes the movement of these cells toward adipose tissue, and thus,
inflammation. It also has a role in the differentiation, homeostasis, and enlargement
of fat cells. In addition, it affects the expression of genes such as glucose
transporter type 4 (GLUT4). Chemerin is a chemical absorption protein which
regulates the activity of dendritic cells (DCs) and macrophages through the G
protein-coupled receptor of CMKL1. Chemerin is secreted in an inactive form and
as prochemerin, and is activated through connection with C-terminal domain and
by inflammation and coagulation serine proteases (4, 9, 10). The results of
some human subject researches have shown a relationship between chemerin and
metabolic syndrome, obesity, insulin resistance, and inflammation. Jialal et
al. found that the level of this adipokine in plasma and adipose tissue was
higher among individuals with metabolic syndrome compared to healthy
individuals, and was correlated with insulin resistance and inflammation
factors, and lipid profile (11). Moreover, Ali et al. reported that the level
of this adipokine was higher in those with metabolic syndrome compared with
healthy individuals, and was related with lipid profile, insulin resistance, and
risk of CVD incidence (4). However, results regarding the relationship of
chemerin with many metabolic syndrome parameters such as age, lipid factors,
and blood pressure are contradictory (4, 10).
Coimbra et al.
found that serum chemerin and leptin levels in elderly individuals with type 2
diabetes have a correlation with obesity and duration of illness, and increase
with increased BMI and illness duration; however, adiponectin has an inverse
relationship with obesity and illness duration (12). Elsebai et al., in their
study on patients with type 2 diabetes, reported that serum chemerin and beta-2
microglubulin levels in these patients were related to incidence of diabetic
nephropathy (13). They concluded that adipokine and beta-2 microglublin can be
predictive markers for incidence of nephropathy among individuals with diabetes
(13). Aksan et al. showed that serum chemerin level was higher and was related
with increased risk of CAD in individuals with metabolic syndrome and coronary
artery disease (CAD) compared to individuals with metabolic syndrome alone
(14).
The present study
was conducted with the aim of determining serum chemerin level in individuals
with metabolic syndrome in comparison to healthy individuals in Rafsanjan,
Iran.
Material and Methods
The statistical
population of the present descriptive study consisted of individuals with
metabolic syndrome referring to physicians in Rafsanjan in 2016. Their condition
was affirmed through clinical examination by a specialist and measurement of
metabolic syndrome indices (waist circumference, systolic and diastolic blood
pressure, triglyceride, fasting glucose level, and HDL). Healthy individuals
were selected from among students and personnel of Rafsanjan University of
Medical Sciences through convenience sampling after referring to the laboratory
of the School of Medicine and based on the results of experiments and a physician’s
diagnosis. These individuals were entered into the study after signing a
consent form. The number of participants and sample volume of each group were
calculated based on the study by Jialal et al. (11) and using the following
equation. The number of 22 participants per group was determined; however, due
to possibility of sample loss, a greater number of individuals were entered into
the study.
n2
= k × n1, … n1 = [( Z1-α/2 + Z1-β)2
× (σ12 + σ22/k)]/∆2
In
the above equation:
α
= 0.05 → Z1-α/2 = 1.96
β
= 0.20 → Z1-β = 0.85
σ1
= 64 ng/ml
Based on this
equation, the standard deviation of serum chemerin level in individuals with
metabolic syndrome (σ2) was determined as 53 ng/ml, and standard
deviation of serum chemerin level in individuals without metabolic syndrome (K)
as 1. Moreover, an equal sample volume was determined for the two groups (∆
= 50 ng/ml).
The minimum difference
in mean serum chemerin level in the two groups which was clinically significant
was 22 (nCase = nControl ≈ 22). The exclusion
criteria consisted of presence of CVD, acute pulmonary disease, hepatitis B and
C, Cushing's syndrome, polycystic ovary syndrome (PCOS), and HIV/AIDS, and use
of lipid-lowering drugs, glucocorticoids (GCs), and antipsychotics (15, 16). Metabolic
syndrome was diagnosed based on the National Cholesterol Education
Program/Adult Treatment Panel III (NCEP/ATP III). Based on this guideline, 3 of
the following 5 criteria must be true for the individual (17).
1-
Systolic blood pressure equal to or higher than 135
mmHg, diastolic blood pressure of equal to or higher than 85 mmHg, or use of
antihypertensive drugs
2-
Central obesity: This criterion has been defined as
waist circumference and must be more than 102 cm in men and 88 cm in women.
3-
Fasting serum triglyceride level of higher than 150
mg/dl (1.7 mmol/l)
4-
Fasting serum HDL level of lower than 40 mg/dl (1
mmol/l) in men and lower than 50 mg/dl (1.3 mmol/l) in women
5-
Fasting glucose level of more than 110 mg/dl
The control group,
who were matched in terms of age and gender with the metabolic syndrome group,
did not have metabolic syndrome based on the NCEP/ATP III, or any of the
illnesses listed in the exclusions criteria based on a physician’s approval.
First, written informed consents were obtained from all participants. Then,
their name, surname, age, and gender were recorder. The factors of height,
weight, waist circumference, hip circumference, and systolic and diastolic
blood pressure were measured by a physician. After 12 hours of fasting, 10 ml
blood samples were obtained from the participants and placed in a centrifuge (3000
rpm) for 5-10 minutes in order to separate serum from coagulated blood. Then,
the transparent liquid on the surface was removed using a pipette, and placed
in microtubes and stored in -20 °C for further examinations (4, 8, 11).
Assessment of
biochemical factors:
Lipid factors of HDL, LDL, triglyceride, and blood sugar were measured using
the BT4500 (Biotechnica, Italy).
Assessment of
serum chemerin and insulin levels:
ELISA kits were used to measure serum chemerin (Zellbio, Germany) and insulin
levelıs (Monobind, USA).
Assessment of insulin
resistance index:
This index was calculated using the relevant equation (18).
All data collected
in the questionnaires were entered into SPSS software (version 18, SPSS Inc.,
Chicago, IL, USA). Results of quantitative variables are represented as mean ±
SD and qualitative variables as number (%). Independent two-sample t-test was
used to compare mean of quantitative variables between individuals with
metabolic syndrome and healthy individuals. Moreover, the Pearson correlation
coefficient was used to assess the relationship between quantitative variables in
individuals with metabolic syndrome. The significant level in all tests was
determined as 0.05.
Results
The study
participants consisted of 31 individuals with metabolic syndrome (11 men and 20
women) with mean age of 42.10 ± 12.06 years and 25 controls (14 men and 11
women) with mean age of 37.52 ± 8.96 years. Statistical tests showed no
significant difference between mean age of the two groups (P=0.109). Furthermore,
chi-square test did not show a significant difference in the gender prevalence
distribution of the two groups (P = 0.125).
The results of
statistical tests are presented in table 1. Based on the results, serum
chemerin level was significantly higher in the metabolic syndrome group
compared to the control group (P = 0.009). Moreover, mean BMI (P < 0.001),
waist circumference (P < 0.001), systolic blood pressure (P = 0.001),
diastolic blood pressure (P< 0.001), insulin resistance (P = 0.005), and
triglyceride (P < 0.001) was significantly higher in the metabolic syndrome
group compared to the control group. However, mean HDL was significantly higher
in the control group compared to the patient group (P = 0.007).
Table 1:
The level of the studied factors in the metabolic syndrome and control groups
(Mean ± SD)
Variable |
Metabolic syndrome group |
Control group |
P-value* |
Height (cm) |
165.32 ± 9.68 |
169.32 ± 10.21 |
0.140 |
Weight (Kg) |
89.23 ± 16.29 |
77.20
± 15.17 |
0.006 |
Body mass index (Kg/M2) |
32.71 ± 5.93 |
26.76
± 3.47 |
< 0.001 |
Waist circumference |
113.10 ± 14.09 |
94.88
± 10.72 |
< 0.001 |
Hip circumference |
120.61 ± 15.94 |
105.64
± 8.70 |
< 0.001 |
Waist to hip circumference ratio |
0.94 ± 0.07 |
0.90
± 0.07 |
0.018 |
Systolic blood pressure (mmHg) |
126.87 ± 12.06 |
114.96
± 12.91 |
0.001 |
Diastolic blood pressure (mmHg) |
81.61 ± 8.20 |
73.04
± 8.86 |
< 0.001 |
Serum insulin level (mg/dl) |
7.57 ± 1.86 |
6.59
± 1.77 |
0.049 |
Fasting serum glucose level (mg/dl) |
106.00 ± 13.63 |
91.88 ± 10.29 |
< 0.001 |
High-density lipoprotein (mg/dl) |
44.29 ± 7.74 |
49.92
± 7.03 |
0.007 |
Triglyceride (mg/dl) |
191.90 ± 74.11 |
104.20
± 55.22 |
< 0.001 |
low-density lipoprotein (mg/dl) |
100.10
± 27.26 |
96.44
± 22.27 |
0.590 |
Insulin resistance index (HOMA-IR) |
2.01 ± 0.67 |
1.52
± 0.56 |
0.005 |
Chemerin (ng/ml) |
806.83 ± 153.63 |
180.46
± 194.88 |
0.009 |
*
Independent two-sample t-test with significant level of < 0.05
Table 2 presents
the Pearson correlation coefficient of serum chemerin level and metabolic
syndrome indices in individuals with metabolic syndrome. Based on the results,
serum chemerin level had no significant relationship with any of the studied
factors (P >0.05).
Table 2: The
relationship between serum chemerin level and metabolic syndrome indices in
individuals with metabolic syndrome
Variable |
Pearson correlation coefficient (r) |
P-value |
Height |
0.061 |
0.744 |
Weight |
0.319 |
0.080 |
Body mass index |
0.253 |
0.169 |
Waist circumference |
0.356 |
0.051 |
Hip circumference |
0.261 |
0.156 |
Waist to hip circumference ratio |
0.185 |
0.320 |
Systolic blood pressure |
0.088 |
0.636 |
Diastolic blood pressure |
0.028 |
0.880 |
Serum insulin level |
0.155 |
0.404 |
Fasting serum glucose level |
0.191 |
0.302 |
HDL |
0.305 |
0.096 |
TG |
0.133 |
0.475 |
LDL |
0.240 |
0.193 |
HOMA-IR |
0.175 |
0.399 |
Age |
0.046 |
0.804 |
HDL: High-density ılipoprotein; TG: Triglyceride; LDL: Low-density lipoprotein;
HOMA-IR: Insulin resistance indexı
Discussion
Adipokines are
polypeptides produced and secreted by adipose tissue and are associated with
functions such as insulin resistance, inflammation, and blood pressure
regulation (7, 8). Some human subject studies have reported a relationship
between chemerin and metabolic syndrome, obesity, insulin resistance, and inflammation
(4). However, some other studies have dismissed the presence of this
relationship (19). Thus, the aim of the present study was the determination of
serum chemerin level and its relationship with obesity and insulin resistance
in individuals with metabolic syndrome in Rafsanjan.
The present study
was conducted on 31 individuals with metabolic syndrome and 25 healthy
individuals (control group). The two groups did not differ significantly in
terms of age and gender. BMI, waist circumference, systolic and diastolic blood
pressure, insulin resistance index, serum insulin and triglyceride levels, and fasting
serum glucose level were significantly higher in the metabolic syndrome group
compared to the control group. Nevertheless, HDL was higher in the control
group in comparison with the patient group. There was no significant difference
between the groups in terms of LDL and mean height. Data analysis showed that
serum chemerin level was significantly higher in the metabolic syndrome group
compared with the control group.
These findings are
consistent with the results of many previous studies which have reported higher
serum chemerin levels in individuals with metabolic syndrome in comparison to a
control group (11, 20, 21). Bozaoglu et al. found that serum chemerin level was
higher in individuals with metabolic syndrome compared to healthy individuals
in a Mexican-American population and was related to many indices of this
syndrome such as triglyceride, HDL, and fasting insulin level (18). They also
found that the level of this adipokine was higher in obese individuals than
thin individuals.
Jialal et al. also
showed that serum chemerin level was higher in individuals with metabolic
syndrome compared to healthy individuals (11). They found that it was related
to increase in factors such as fasting triglyceride and
insulin levels; however, it had an inverse relationship with omentin level and
HDL level in individuals with metabolic syndrome (11). Chu et al. showed that
serum chemerin level was higher in individuals with metabolic syndrome compared
with healthy individuals and was related to factors such as BMI and
triglyceride (19). However, they found that it had an inverse relationship with
adiponectin and acute-phase proteins, and no relationship with pantraksin
enzyme 3, which is an anti-inflammatory agent (19).
Obesity is one of
the most important outcomes of the modern lifestyle and increases the risk of
many diseases (17). There are many markers for obesity such as BMI and waist
circumference. Obesity is accompanied with increased body fat, and in humans,
this adipokine is produced by immune cells and adipose tissues; thus, increased
cell count and adipose tissue results in an increase in the production of this
adipokine (22).
Some studies have
suggested that chemerin is involved in increased insulin resistance in
individuals with metabolic syndrome (4, 11). Nevertheless, no relationship was
observed between chemerin level and insulin resistance in these individuals in
the present study. The lack of relationship between serum chemerin level and
insulin resistance may be due to the presence of different hormones which play
a role in insulin resistance. The insulin resistance effect of chemerin is insignificant
in comparison to these hormones (15).
The present
results suggest that no significant relationship exists between serum chemerin
level and triglyceride, LDL, and HDL. This finding is not in agreement with the
results of some previous studies in this field (11, 20, 21). Based on the
results of these studies, chemerin has an important role in increased LDL and
HDL; this adipokine affects the hepatic cells and increases the level of VLDL
which is a precursor of LDL (16).
Conclusion
Based on the results
of the present study and previous studies, serum chemerin level increases in
individuals with metabolic syndrome. Therefore, changes in serum chemerin level
can be used as a criterion for diagnosis and confirmation of metabolic syndrome,
and the assessment of this adipokine can be effective in the determination of
appropriate treatment methods.
Acknowledgements
The authors would
like to thank the Deputy of Research of Rafsanjan University of Medical
Sciences for the funding of this study and all who participated in this study.
Conflict of interest: None
declared
References
1.
Fatima SS,
Bozaoglu K, Rehman R, Alam F, Memon AS. Elevated chemerin levels in Pakistani
men: an interrelation with metabolic syndrome phenotypes. PLoS One 2013; 8(2):e57113.
2.
.Balistreri
CR, Caruso C, Candore G. The role of adipose tissue and adipokines in
obesity-related inflammatory diseases. Mediators Inflamm 2010; 2010:802078.
3.
Wang D, Yuan GY,
Wang XZ, Jia J, Di LL, Yang L, et al. Plasma chemerin level in metabolic
syndrome. Genet Mol Res 2013; 12(4):5986-91.
4.
Ali TM, Al Hadidi
K. Chemerin is associated
with markers of inflammation and predictors of atherosclerosis in Saudi
subjects with metabolic syndrome and type 2 diabetes mellitus. Beni-Suef
University Journal of Basic and Applied Sciences 2013; 2(2):86-95.
5.
Kaur J. A
comprehensive review on metabolic syndrome. Cardiol Res Pract 2014; 2014:943162.
6.
Emanuela F,
Grazia M, Marco DR, Maria Paola L, Giorgio F, Marco B. Inflammation as a link
between obesity and metabolic syndrome. J Nutr Metab 2012; 2012:476380.
7.
Delavari A,
Forouzanfar MH, Alikhani S, Sharifian A, Kelishadi R. First nationwide study of
the prevalence of the metabolic syndrome and optimal cutoff points of waist
circumference in the Middle East: the national survey of risk factors for
noncommunicable diseases of Iran. Diabetes Care 2009; 32(6):1092-7.
8.
Osman MM,
El-Mageed AIA, El-Hadidi E, Shahin RSK, Mageed NAAA. Clinical utility of serum
chemerin as a novel marker of metabolic syndrome and type 2 diabetes mellitus. Life
science journal 2012; 9(2):1098-108.
9.
Mattern A,
Zellmann T, Beck‐Sickinger
AG. Processing, signaling, and physiological function of chemerin. IUBMB Life
2014; 66(1):19-26.
10. Li
Y, Shi B, Li S. Association between serum chemerin concentrations and clinical indices in obesity
or metabolic syndrome: a meta-analysis. PLoS One 2014; 9(12):e113915.
11. Jialal
I, Devaraj S, Kaur H, Adams-Huet B, Bremer AA. Increased chemerin and decreased
omentin-1 in both adipose tissue and plasma in nascent metabolic syndrome. J Clin Endocrinol
Metab 2013; 98(3):E514-7.
12. Coimbra
S, Brandão Proença J, Santos-Silva A, Neuparth MJ. Adiponectin, leptin,
and chemerin in elderly patients with type 2 diabetes mellitus: a close linkage
with obesity and length of the disease. Biomed Res Int 2014; 2014:701915.
13.
Elsebai AA, Saad
WE, Mahdy MM. Serum chemerin and beta 2-microglobulin in type 2 diabetes: assessment
of diabetic nephropathy. Life science journal 2014; 11(8):992-1000.
14.
Aksan G,
İnci S, Nar G, Soylu K, Gedikli Ö,
Yüksel S, et al. Association of serum chemerin levels with the severity of
coronary artery disease in patients with metabolic syndrome. Int J Clin Exp Med
2014; 7(12):5461-8.
18. Shirai
K. Obesity as the core of the metabolic syndrome and the management of coronary
heart disease. Curr Med Res Opin 2004; 20(3):295-304.
19. Takahashi
M, Takahashi Y, Takahashi K, Zolotaryov FN, Hong KS, Kitazawa R, et al. Chemerin
enhances insulin signaling and potentiates insulin-stimulated glucose uptake in
3T3-L1 adipocytes. FEBS Lett. 2008; 582(5):573-8
22. Sadashiv,
Tiwari S, Paul BN, Kumar S, Chandra A, Dhananjai S, et al. Over expression of
resistin inadipose tissue of the obese induces insulin resistance. World J Diabetes
2012; 3(7):135-41.
* Corresponding author: Mohammad Reza
Hajizadeh,
Molecular Medicine Research Center and Dept. of Clinical Biochemistry, Faculty
of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
E-mail: hajizadehus@yahoo.com