Abstract
BACKGROUND
The observed relationships between visfatin, peroxidases activity, and metabolic syndrome (MetS) are inconsistent; therefore, this study was undertaken to understand these relationships.
METHODS
This cross-sectional study was conducted as a part of the Isfahan Healthy Heart Program, Iran. A blood sample of 90 MetS and non-MetS patients were used to estimate total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C), triglycerides (TGs), fasting blood glucose (FBG), waist circumference (WC), systolic blood pressure (SBP) and diastolic blood pressure (DBP), visfatin and peroxidases activity. Data analysis for MetS group was carried out in two ways. (1) MetS with three components and with > 3 components. (2) MetS with hyperglycemia and without hyperglycemia.
RESULTS
SBP, DBP, WC, FBG, TC, TG, LDL-C, and were higher and HDL-C levels was lower in MetS patients. There was a significant correlation between visfatin levels and peroxidases activity in MetS patients with three components. Levels of visfatin were significantly higher in male as compared to female subjects in the MetS with three components group. There was a significant decrease in peroxidases activity in > 45 years old subjects in the MetS with > 3 components group. A significant correlation was observed between serum visfatin levels and FBG in the MetS without hyperglycemia group.
CONCLUSION
Peroxidases activities in MetS patients can be related to visfatin levels. Gender influences on peroxidases activity probably and was lower in female patients with MetS. Hyperglycemia does not influence peroxidases activities and visfatin levels.
Keywords: Peroxidase, Metabolic Syndrome, Visfatin
Introduction
The prevalence of metabolic syndrome (MetS) has increased in recent decades,1 and has been described as a cluster of multiple, partially or fully expressed, metabolic abnormalities within the single individual that increase the risk of developing cardiovascular disease and diabetes.2,3 In recent years, there has been much interest in the role of free radicals and oxidative stress in the pathogenesis of MetS.4 It has been shown that obesity per se may induce systemic oxidative stress and that increased oxidative stress in accumulated fat is, at least in part, the underlying cause of the dysregulation of adipocytokines and the development of MetS.5 Adipocytokines include adiponectin, leptin, resistin, and visfatin that are secreted from adipose tissue.6
In human pulmonary vascular endothelial cells, visfatin was demonstrated to interact with several proteins mediating oxidative stress and inflammation leading to increased levels of reactive oxygen species.7 Oxidative stress may be defined as an imbalance between the production and degradation of reactive oxygen species. Enzymatic inactivation of reactive oxygen species is achieved mainly by antioxidative enzymes.8 The main antioxidant enzymes are glutathione peroxidase (GPx), superoxide dismutase, catalase, and myeloperoxidase.9 Peroxidases are a family of widespread enzymes which perform distinct tasks. On one hand, they act as preventive antioxidants to detoxify damaging lipid peroxides or other peroxides from blood and organic substrates. On the other hand, these enzymes function as starters for oxidative reactions, thereby generating a source of reactive oxygen species such as hypochlorous acid (HOCl) or hypoiodous acids (HOI).10
Increasing the visfatin levels can be observed in atherosclerosis,11 endothelial dysfunctions,12,13 and renal insufficiency.14 Evidence on possible associations between serum visfatin and metabolic parameters in patients with obesity and diabetes are contradictory.14-18 Takebayashi et al.14 did not find any correlation between visfatin and diabetes, and other study proved that there is a positive correlation between the decrease of visfatin and type 1 diabetes and negative correlation between glycated hemoglobin and visfatin levels.19 Berndt et al.16 and Hammarstedt et al.20 have reported that serum concentration of visfatin is increased in obesity. On the other hand, Pagano et al.21 revealed that plasma visfatin was significantly lower in
obese subjects.
The effect of hyperglycemia on levels of visfatin is discussed. Alexiadou et al.22 finding was discordance with previous study23 demonstrating that visfatin is enhanced by hyperglycemia.
The visfatin levels and peroxidases activity are important in MetS, whereas only very few studies have been conducted to clarify the relationships between visfatin and peroxidases, and these factors and MetS. Therefore, the present study was designed to understand these relationships.
Materials and Methods
Participants
This cross-sectional study was conducted in 2012 as a part of the Isfahan Healthy Heart Program, Iran, (IHHP). IHHP began in 2000 to prevent and control cardiovascular disease risk factors in the Iranian population. This program was conducted in Central Iran. A stratified multi-stage probability sampling method was used in the baseline survey (2001) and the post-intervention in 2007.24
Blood samples (from 90 subjects within the age range of 19-82 years) of IHHP third phase (2006-2007) were used for this study. Samples of subjects with MetS (n = 45) and also without MetS (n = 45), were selected using simple random sampling. MetS defined by the National Cholesterol Education Program Adult Treatment Panel III as the presence of 3 or more of the following criteria: abdominal obesity: waist circumference (WC) ≥ 102 cm in men and ≥ 88 cm in women and 2 or more of the following: systolic blood pressure (SBP) ≥ 130 mmHg and/or diastolic blood pressure (DBP) ≥ 85 mmHg; triglyceride (TG) ≥ 150 mg/dl; high-density lipoprotein cholesterol (HDL-C) < 40 mg/dl in men and < 50 mg/dl in women; fasting blood glucose (FBG) ≥ 110 mg/dl.10 The study protocol was approved by the Medical Ethics Committees of the Isfahan Cardiovascular Research Institute under the Approval No. 91115.
Biochemical and anthropometric measurement
All measurements were conducted using calibrated instruments and standard protocols by a trained team of general physicians and nurses. Blood samples were collected from both groups to measure the biochemical factors following a 12-h fasting. All the blood sampling procedures were performed in the central laboratory of the Isfahan Cardiovascular Research Institute. FBG and serum lipids, including serum total cholesterol (TC), TG and HDL-C levels were detected by an enzymatic method using an Elan 2000 auto analyzer (Ependorf, Hamburg, Germany). Low-density lipoprotein-cholesterol (LDL-C) was calculated (in serum samples with TG ≤ 400 mg/dl) according to the Friedewald formula.25
The separated serum was stored at −70 °C until the measurement of visfatin levels. Visfatin levels were assayed by ELISA kit (BioVendor Laboratory Medicine Inc., Canada and Mexico, USA). Determination of peroxidases activity in the serum was done by the reaction of endogenous peroxidases with hydrogen peroxide, using 3,5,3',5'-tetramethylbenzidine as the chromogenic substrate.26 A mercury sphygmomanometer with a cuff size suitable for each subject was used for measuring sitting blood pressure twice from the right arm according to World Health Organization criteria. The mean of two measurements of korotkoff phase I and phase IV was recorded for SBP and DBP, respectively. WC was determined from the point halfway between the lower border of ribs and the iliac crest in a horizontal plane.27
Statistical analysis
Statistical analyses were performed using SPSS for Windows (version 15; SPSS Inc., Chicago, IL, USA). Data were presented as means ± standard deviation. Data analysis for MetS group was carried out in two ways: (1) MetS with three components and with > 3 components. (2) MetS with hyperglycemia and without hyperglycemia. Analysis of covariance was used to compare factors between groups with adjusting age and sex. Also for significant differences, Bonferroni multiple comparison was applied. For comparing visfatin levels and peroxidases activity in groups based on age and sex (without adjustment) Kruskal-Wallis test was used. Mann-Whitney tests with Bonferroni adjustment used to multiple comparisons. Investigation of correlation between visfatin levels and peroxidases activity and also between these two factors with parameters of MetS was assessed using spearman and partial correlation. P-value of < 0.05 was considered to be statistically significant.
Results
Findings on the values of the biochemical factors are summarized in table 1. The MetS subjects had significantly higher values of SBP, DBP, WC, FBG, TC, TG, LDL-C, and lower levels of HDL-C than the non-MetS subjects. There was no significant difference in serum levels of visfatin and peroxidases activity between MetS and non-MetS groups.
Table 1.
Demographic, clinical, and laboratory variables adjusted for age and sex in patient with and without metabolic syndrome
| Characteristics | Non-MetS (n = 45) | MetS with three components (n = 29) | MetS with > 3 components (n = 16) | P | Non-MetS (n = 45) | MetS with hyperglycemia (n = 17) | MetS without hyperglycemia (n = 28) | P |
|---|---|---|---|---|---|---|---|---|
| Visfatin (mg/ml) | 2.83 ± 3.43 | 3.02 ± 3.27 | 3.17 ± 3.47 | 0.944 | 2.83 ± 3.43 | 3.07 ± 2.10 | 3.07 ± 2.61 | 0.464 |
| Peroxidase activity (mU/ml) | 19.23 ± 30.03 | 3.76 ± 27.91 | 7.77 ± 30.03 | 0.050 | 20.03 ± 30.16 | 8.17 ± 18.42 | 8.17 ± 22.93 | 0.191 |
| Total cholesterol (mg/dl) | 180.57 ± 34.72** | 207.08 ± 32.28* | 195.87 ± 34.74 | 0.006 | 179.98 ± 34.59** | 209.20 ± 33.22* | 200.00 ± 33.12 | 0.007 |
| Triglycerides (mg/dl) | 100.19 ± 95.92**,€ | 160.08 ± 89.27*,€ | 261.18 ± 96.01*,** | 0.001 | 106.20 ± 10.17**,€ | 219.00 ± 9.79* | 174.74 ± 9.74* | 0.001 |
| High-density lipoprotein cholesterol (mg/dl) | 46.97 ± 9.74€ | 41.86 ± 9.01€ | 33.07 ± 9.75*,** | 0.001 | 46.49 ± 101.35€ | 40.83 ± 97.49 | 38.00 ± 97.15* | 0.004 |
| low-density lipoprotein cholesterol (mg/dl) | 113.39 ± 29.41** | 132.54 ± 27.40* | 113.54 ± 29.44 | 0.008 | 112.31 ± 30.16 | 127.33 ± 20.03* | 126.08 ± 28.89* | 0.049 |
| Fasting blood glucose (mg/dl) | 84.21 ± 18.98€ | 91.83 ± 17.63 | 104.64 ± 19.00* | 0.003 | 85.09 ± 16.04** | 112.81 ± 15.42*,€ | 85.16 ± 15.36*,** | 0.001 |
| Systolic blood pressure (mmHg) | 114.12 ± 17.86**,€ | 125.48 ± 16.31* | 130.42 ± 17.39* | 0.005 | 114.42 ± 17.86**,€ | 127.66 ± 12.56* | 126.70 ± 16.59* | 0.007 |
| Diastolic blood pressure (mmHg) | 73.32 ± 11.36*,€ | 82.80 ± 10.39* | 85.63 ± 11.07* | 0.001 | 114.42 ± 17.86**,€ | 85.18 ± 10.82* | 82.82 ± 10.52* | 0.001 |
| Waist circumference (cm) | 88.37 ± 11.86** | 97.00 ± 10.85* | 92.93 ± 11.45 | 0.009 | 88.12 ± 11.92** | 96.68 ± 11.22* | 95.05 ± 11.02 | 0.016 |
The results are expressed as mean values ± standard deviation (SD); P-values are significant P < 0.05;
Significant difference with non-MetS;
Significant difference with MetS with three components or with hyperglycemia;
Significant difference with MetS with > 3 components or without hyperglycemia;
Analysis of covariance was used; MetS: Metabolic syndrome
Table 2 shows the correlation between visfatin levels and peroxidases activity in the studied groups. There was a significant correlation between visfatin levels and peroxidases activity in MetS subjects with three components whilst non-significant correlation was observed between these factors in the other groups (non-MetS, MetS with > 3 components, and MetS with and without hyperglycemia).
Table 2.
Correlation between visfatin levels and peroxidase activity in two non-metabolic syndrome and metabolic groups
| Biochemical factors | Groups | Spearman’s correlation with visfatin levels (mg/ml) | P |
|---|---|---|---|
| Peroxidase activity (mU/ml) | Non-MetS (n = 45) | 0.094 | 0.581 |
| MetS with three components (n = 29) | 0.769 | 0.001 | |
| MetS with > 3 components (n = 16) | 0.315 | 0.253 | |
| MetS with hyperglycemia (n = 17) | −0.244 | 0.328 | |
| MetS without hyperglycemia (n = 28) | 0.189 | 0.345 |
P-values are significant P < 0.05; Spearman correlation was used; MetS: Metabolic syndrome
Changes in visfatin levels and peroxidases activity based on sex and age were compared between non-MetS, MetS with three components, and MetS with > 3 components (Table 3) and between non-MetS, MetS with hyperglycemia and MetS without hyperglycemia (Table 4). There was no significant difference in serum visfatin levels between MetS and non-MetS groups in sex and age groups. For peroxidases activity, there was significant difference between non-MetS and MetS with three components groups in female subjects and also between MetS with three components and with > 3 components groups in 19-44 years old subjects. Peroxidases activity did not significantly changed between non-MetS, MetS with hyperglycemia and MetS without hyperglycemia in sex and age groups. Levels of visfatin were significantly higher in male subjects than female in the MetS with three components. There was significant reduction in peroxidases activity in > 45 years old subjects in comparison with 19-44 years old subjects in the MetS with > 3 components.
Table 3.
Visfatin levels and glutathione peroxidase activity based on sex and age in non-metabolic syndrome and metabolic syndrome (with three components, with > 3 components of metabolic syndrome) groups
| Variable | Non-metabolic syndrome (n = 45) | Metabolic syndrome with three components (n = 29) | Metabolic syndrome with > 3 components (n = 16) | P |
|---|---|---|---|---|
| Visfatin (mg/ml) | ||||
| Sex | ||||
| Female (n = 49) | 2.80 ± 3.51 | 1.70 ± 1.10 | 3.14 ± 2.41 | 0.206 |
| Male (n = 41) | 2.85 ± 2.17 | 4.33 ± 5.12 | 3.00 ± 1.76 | 0.841 |
| P | 0.435 | 0.022 | 0.842 | |
| Age | ||||
| 19-45 year (n = 56) | 2.93 ± 3.29 | 3.11 ± 4.52 | 2.80 ± 2.94 | 0.963 |
| > 45 year (n = 34) | 2.40 ± 2.09 | 2.73 ± 2.84 | 3.16 ± 1.58 | 0.277 |
| P | 0.716 | 0.968 | 0.389 | |
| Peroxidase activity (mU/ml) | ||||
| Sex | ||||
| Female (n = 49) | 20.46 ± 35.35** | 1.64 ± 1.53* | 12.57 ± 28.89 | 0.043 |
| Male (n = 41) | 23.71 ± 41.90 | 4.21 ± 6.80 | 14.23 ± 30.76 | 0.376 |
| P | 0.314 | 0.060 | 0.272 | |
| Age | ||||
| 19-45 year (n = 56) | 22.91 ± 37.80 | 3.72 ± 6.58 £ | 43.06 ± 45.31** | 0.022 |
| > 45 year (n = 34) | 16.62 ± 37.38 | 1.90 ± 1.24 | 2.03 ± 1.67 | 0.102 |
| P | 0.598 | 0.853 | 0.005 |
The results are expressed as mean values ± standard deviation (SD); P-values are significant P < 0.05; Kruskal-Wallis test and Mann-Whitney tests (for multiple comparison) was used;
Significant difference with non-MetS;
Significant difference with MetS with three components or with hyperglycemia;
Significant difference with MetS with > 3 components or without hyperglycemia
Table 4.
Visfatin levels and glutathione peroxidase activity based on sex and age in non-metabolic syndrome and metabolic syndrome (with hyperglycemia and without hyperglycemia) groups
| Variable | Non metabolic syndrome (n = 45) | Metabolic syndrome with hyperglycemia (n = 17) | Metabolic syndrome without hyperglycemia (n = 28) | P |
|---|---|---|---|---|
| Visfatin (mg/ml) | ||||
| Sex | ||||
| Female | 2.80 ± 3.51 | 2.00 ± 1.27 | 2.25 ± 2.05 | 0.838 |
| Male | 2.85 ± 2.17 | 2.50 ± 1.60 | 4.41 ± 4.79 | 0.778 |
| P | 0.435 | 0.489 | 0.065 | |
| Age | ||||
| 19-44 years | 2.93 ± 3.39 | 1.66 ± 1.32 | 4.00 ± 5.16 | 0.103 |
| > 45 years | 2.40 ± 2.09 | 2.63 ± 2.36 | 3.12 ± 2.84 | 0.399 |
| P | 0.716 | 0.078 | 0.804 | |
| Peroxidase activity (mU/ml) | ||||
| Sex | ||||
| Female | 20.46 ± 35.35 | 4.83 ± 15.65 | 8.87 ± 22.12 | 0.052 |
| Male | 23.71 ± 41.90 | 1.79 ± 1.64 | 9.28 ± 23.78 | 0.581 |
| P | 0.314 | 0.077 | 0.108 | |
| Age | ||||
| 19-44 years | 22.91 ± 37.80 | 5.38 ± 8.67 | 16.89 ± 32.63 | 0.514 |
| > 45 years | 16.62 ± 37.38 | 1.95 ± 1.63 | 1.97 ± 1.34 | 0.052 |
| P | 0.598 | 0.394 | 0.333 |
The results are expressed as mean values ± standard deviation (SD); P-values are significant P < 0.05; Kreskas-Wallis test and Mann- Whitney tests (for multiple comparison) was used
Correlation between visfatin levels and peroxidases activity with components of MetS are provided in table 5. There was no significant correlation between serum visfatin levels and lipid profile, FBG, SBP, DBP, and WC in MetS and non-MetS groups except visfatin and FBG in the MetS without hyperglycemia subjects. No statistically significant correlation was found between peroxidases activity and studied factors.
Table 5.
Correlation of visfatin levels and glutathione peroxidase activity adjusted for age and sex with parameters of metabolic syndrome
| Characteristic | TC (mg/dl) | TG (mg/dl) | HDL (mg/dl) | LDL (mg/dl) | FBG (mg/dl) | SBP (mmHg) | DBP (mmHg) | WC (cm) |
|---|---|---|---|---|---|---|---|---|
| Visfatin (mg/ml) | ||||||||
| Non-MetS (n = 45) | −0.078 | −0.056 | −0.198 | −0.013 | 0.036 | −0.027 | 0.054 | 0.094 |
| P | 0.648 | 0.740 | 0.240 | 0.937 | 0.832 | 0.879 | 0.759 | 0.596 |
| MetS with three components (n = 29) | 0.193 | 0.291 | −0.034 | 0.046 | −0.348 | 0.134 | 0.058 | 0.257 |
| P | 0.308 | 0.118 | 0.857 | 0.809 | 0.060 | 0.489 | 0.766 | 0.186 |
| MetS with > 3 components (n = 16) | −0.321 | 0.198 | 0.054 | −0. 007 | −0.100 | 0.284 | 0.448 | −0.231 |
| P | 0.458 | 0.480 | 0.848 | 0.979 | 0.722 | 0.305 | 0.094 | 0.408 |
| MetS with hyperglycemia (n = 17) | 0.286 | 0.386 | −0.144 | −0.002 | 0.151 | 0.221 | 0.338 | 0.373 |
| P | 0.250 | 0.113 | 0.570 | 0.994 | 0.549 | 0.395 | 0.185 | 0.186 |
| MetS without hyperglycemia (n = 28) | 0.175 | 0.327 | −0.010 | −0.015 | −0.512 | 0.145 | 0.065 | −0.032 |
| P | 0.382 | 0.096 | 0.960 | 0.939 | 0.006 | 0.469 | 0.749 | 0.876 |
| Peroxidase activity (mU/ml) | ||||||||
| Non-MetS (n = 45) | −0.117 | −0.206 | −0.184 | −0.033 | −0.220 | −0.183 | −0.256 | −0.130 |
| P | 0.491 | 0.221 | 0.277 | 0.847 | 0.190 | 0.292 | 0.138 | 0.464 |
| MetS with three components (n = 29) | −0.093 | −0.093 | 0.084 | −0.086 | −0.302 | 0.058 | −0.002 | 0.024 |
| P | 0.617 | 0.618 | 0.655 | 0.646 | 0.099 | 0.759 | 0.991 | 0.903 |
| MetS with > 3 components (n = 16) | −0.321 | −0.313 | −0.070 | 0.012 | 0.164 | 0.168 | 0.106 | −0.037 |
| P | 0.225 | 0.238 | 0.796 | 0.966 | 0.543 | 0.535 | 0.696 | 0.890 |
| MetS with hyperglycemia (n = 17) | −0.291 | −0.363 | −0.007 | 0.069 | 0.169 | −0.082 | −0.367 | −0.117 |
| P | 0.241 | 0.138 | 0.980 | 0.784 | 0.503 | 0.755 | 0.147 | 0.653 |
| MetS without hyperglycemia (n = 28) | −0.113 | 0.071 | −0.204 | −0.114 | −0.247 | −0.183 | −0.256 | 0.062 |
| P | 0.560 | 0.715 | 0.289 | 0.555 | 0.197 | 0.292 | 0.138 | 0.755 |
P-values are significant P < 0.05; Partial correlation was used; MetS: Metabolic syndrome; TC: Total cholesterol; TG: Triglycerides; HDL: High-density lipoprotein cholesterol; LDL: Low-density lipoprotein cholesterol; FBG: Fasting blood glucose; SBP: Systolic blood pressure; DBP: Diastolic blood pressure; WC: Waist circumference
Discussion
The findings of the current study provide evidence-based information about the impacts of visfatin levels and peroxidases activity on parameters of MetS. There was positive correlation between visfatin levels and peroxidases activity in MetS subjects with three components.
Peroxidases activity was higher in MetS with three components than the non-MetS in people female subjects. Peroxidases activity reduced with increasing age in the MetS with > 3 components group and visfatin levels enhanced in male subjects in the MetS with three components group.
Activities of antioxidant enzymes protect against oxidative stress in MetS.28 Oxidative stress is associated with many of the components of the syndrome, leading to the concept that the amelioration of risk factors comprising MetS, including insulin resistance, elevated blood pressure, elevated lipid levels, inflammation and endothelial dysfunction may ameliorate oxidative stress and thus curtail the progression of metabolic disease complications.29
The results by Vavrova et al.28 implicated an increased oxidative stress in MetS and a decreased antioxidative defense that correlated with some laboratory (TG, HDL-C) and clinical (WC, BP) components of MetS.
Here, we showed a higher serum visfatin levels in patients with MetS however this elevation was no significant. Consistent with our findings, studies have shown elevated serum visfatin levels patients with MetS when compared to individuals without MetS.30-32 Primary investigation on visfatin showed the insulin-mimicking effect of this hormone.33 Hence, one would conclude that an elevated visfatin levels in patients with MetS is due to insulin resistance. Cekmez et al.34 suggested visfatin as a marker of insulin resistance. Inconsistently, Esteghamati et al.32 showed a higher visfatin concentration, independent of insulin resistance, in type 2 diabetes. Furthermore in two other separate studies, Berndt et al.16 and Haider et al.35 showed that visfatin levels were not correlated with insulin resistance and lipid parameters in patients with type 2 diabetes and obesity. A study by Kaminska et al.36 revealed elevated levels of visfatin in obese subjects did not correlate with the majority of anthropometric parameters. They suggested that elevated visfatin levels are associated with the distribution of adipose tissue characteristic of gynoid rather than visceral obesity.
Yen et al.37 reported, the subjects suffering from MetS might be under higher oxidative stress, resulting in low levels of antioxidant enzyme activities. MetS is a type of metabolic disorder rather than a disease. Subjects with MetS might be under higher oxidative stress; antioxidant enzymes are the first line of defense against reactive oxygen species and may decrease to adjust to higher levels of oxidative stress.38 In addition, MetS subjects in general were typically abdominally obese. Obesity is also an oxidative burden that may lead to the reduction of antioxidant enzymes activities.39 Oxidative stress associate with advancing age.40 Therefore, the findings of our study confirm the previous study’s results.
Mecocci et al.41 concluded that senescence seems be associated with a decline in nutritional antioxidants together with an increase in antioxidant enzyme activity; the latter understood as an adaptive response to an increased level of oxidation products.
In our study, peroxidase activity decreased with age increase in all of groups, especially MetS with > 3 components.
Because inhibition of cholesteryl ester transfer protein increases HDL-C level and decreases LDL levels,42,43 one explanation of visfatin in cholesterol homeostasis may be via inhibition of cholesteryl ester transfer protein. The sex difference of correlation between visfatin and cholesterol levels may be due to estrogen effect. Estrogen may modulate visfatin to inhibit cholesteryl ester transfer protein in cholesterol homeostasis.44
Some studies had examined the relationship between plasma visfatin concentration and age in different populations. However, the results were inconsistent. A negative correlation was found in women with gestational diabetes mellitus,45 but a positive correlation in patients with MetS.46 The obtained results by Dogru et al.15 were consistent with this study.
Decrease of oxidative stress association with elevating the expression of antioxidant enzymes, superoxide dismutase, catalase, glutathione, and GPx in addition to lowering LDL-C, TG, and CRP and elevating HDL-C.47 Chen et al.48 reported the value of WC was significantly correlated with and GPx activities in MetS patients.
We did not find any correlations between visfatin and lipid profile, glucose, and other measured parameters. Our results are different from previous reports. Contrary to our results, in multiple step-wise regressions analysis by Zhong et al.49 LDL-C was identified as the independent factor that influences serum visfatin. They concluded visfatin may correlate with the metabolism of cholesterol. Furthermore in the study by Chen et al.,45 serum visfatin correlated negatively with LDL-C in women with MetS. Fukuhara et al.33 identified visfatin as an adipocytokine predominantly secreted from visceral adipocytes. Computed tomographic scan demonstrated that plasma visfatin levels correlated strongly with the visceral fat area and weakly with the subcutaneous fat area in 101 male and female human subjects.33 One of the study revealed visfatin levels correlate with WC and waist-hip ratio.44 However, previous reports16,49,50 and this study have not found this correlation. The discrepancy between the studies may be explained by differences in patient populations or different methods of sample collection51 and detection.52
Conclusion
Peroxidases activities in MetS patients can be related to visfatin levels. Gender influences on GPx activity probably and was lower in female patients with MetS. Hyperglycemia does not influence peroxidases activities and visfatin levels.
Suggestions
Further study needs to be done to clarify the exact role of visfatin in MetS, especially homeostasis of lipid. According to the menstrual cycle influences on levels of visfatin and peroxidases activity and thus it should be considered. The correlation between other antioxidant enzymes such as superoxide dismutase, catalase, and glutathione with visfatin is investigated in the future.
Study limitations
Our study had some limitations. First, the number of participants of each both groups was small. Second, this study was a cross-sectional study, and therefore, no causal relationship could be defined. Third, age range of the participants was wide that may be influencing on peroxidases activity and plasma visfatin levels.
Acknowledgments
This study was extracted from a thesis by Mohammad Bolhasani. The authors gratefully acknowledge the personnel of School of Pharmacy and Isfahan Cardiovascular Research Institute, especially those in the Surveillance Department and IHHP Evaluation Committee for their close cooperation.
Footnotes
Conflicts of Interest
Authors have no conflict of interests.
REFERENCES
- 1.Dutra ES, de Carvalho KM, Miyazaki E, Hamann EM, Ito MK. Metabolic syndrome in central Brazil: prevalence and correlates in the adult population. Diabetol Metab Syndr. 2012;4(1):20. doi: 10.1186/1758-5996-4-20. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Aydin M, Bulur S, Alemdar R, Yalcin S, Turker Y, Basar C, et al. The impact of metabolic syndrome on carotid intima media thickness. Eur Rev Med Pharmacol Sci. 2013;17(17):2295–301. [PubMed] [Google Scholar]
- 3.Akyol B, Boyraz M, Aysoy C. Relationship of epicardial adipose tissue thickness with early indicators of atherosclerosis and cardiac functional changes in obese adolescents with metabolic syndrome. J Clin Res Pediatr Endocrinol. 2013;5(3):156–63. doi: 10.4274/Jcrpe.1064. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Khan SR. Stress oxidative: nephrolithiasis and chronic kidney diseases. Minerva Med. 2013;104(1):23–30. [PubMed] [Google Scholar]
- 5.Matsuda M, Shimomura I. Increased oxidative stress in obesity: implications for metabolic syndrome, diabetes, hypertension, dyslipidemia, atherosclerosis, and cancer. Obes Res Clin Pract. 2013;7(5):e330–e341. doi: 10.1016/j.orcp.2013.05.004. [DOI] [PubMed] [Google Scholar]
- 6.Jaleel A, Aheed B, Jaleel S, Majeed R, Zuberi A, Khan S, et al. Association of adipokines with obesity in children and adolescents. Biomark Med. 2013;7(5):731–5. doi: 10.2217/bmm.13.41. [DOI] [PubMed] [Google Scholar]
- 7.Buldak RJ, Polaniak R, Buldak L, Mielanczyk L, Kukla M, Skonieczna M, et al. Exogenous administration of visfatin affects cytokine secretion and increases oxidative stress in human malignant melanoma Me45 cells. J Physiol Pharmacol. 2013;64(3):377–85. [PubMed] [Google Scholar]
- 8.Wojcik KA, Kaminska A, Blasiak J, Szaflik J, Szaflik JP. Oxidative stress in the pathogenesis of keratoconus and Fuchs endothelial corneal dystrophy. Int J Mol Sci. 2013;14(9):19294–308. doi: 10.3390/ijms140919294. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Bellanti F, Matteo M, Rollo T, De RF, Greco P, Vendemiale G, et al. Sex hormones modulate circulating antioxidant enzymes: Impact of estrogen therapy. Redox Biol. 2013;1(1):340–6. doi: 10.1016/j.redox.2013.05.003. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Grundy SM. Metabolic syndrome pandemic. Arterioscler Thromb Vasc Biol. 2008;28(4):629–36. doi: 10.1161/ATVBAHA.107.151092. [DOI] [PubMed] [Google Scholar]
- 11.Dahl TB, Yndestad A, Skjelland M, Oie E, Dahl A, Michelsen A, et al. Increased expression of visfatin in macrophages of human unstable carotid and coronary atherosclerosis: possible role in inflammation and plaque destabilization. Circulation. 2007;115(8):972–80. doi: 10.1161/CIRCULATIONAHA.106.665893. [DOI] [PubMed] [Google Scholar]
- 12.Stofkova A. Resistin and visfatin: regulators of insulin sensitivity, inflammation and immunity. Endocr Regul. 2010;44(1):25–36. doi: 10.4149/endo_2010_01_25. [DOI] [PubMed] [Google Scholar]
- 13.Wang LS, Yan JJ, Tang NP, Zhu J, Wang YS, Wang QM, et al. A polymorphism in the visfatin gene promoter is related to decreased plasma levels of inflammatory markers in patients with coronary artery disease. Mol Biol Rep. 2011;38(2):819–25. doi: 10.1007/s11033-010-0171-6. [DOI] [PubMed] [Google Scholar]
- 14.Takebayashi K, Suetsugu M, Wakabayashi S, Aso Y, Inukai T. Association between plasma visfatin and vascular endothelial function in patients with type 2 diabetes mellitus. Metabolism. 2007;56(4):451–8. doi: 10.1016/j.metabol.2006.12.001. [DOI] [PubMed] [Google Scholar]
- 15.Dogru T, Sonmez A, Tasci I, Bozoglu E, Yilmaz MI, Genc H, et al. Plasma visfatin levels in patients with newly diagnosed and untreated type 2 diabetes mellitus and impaired glucose tolerance. Diabetes Res Clin Pract. 2007;76(1):24–9. doi: 10.1016/j.diabres.2006.07.031. [DOI] [PubMed] [Google Scholar]
- 16.Berndt J, Kloting N, Kralisch S, Kovacs P, Fasshauer M, Schon MR, et al. Plasma visfatin concentrations and fat depot-specific mRNA expression in humans. Diabetes. 2005;54(10):2911–6. doi: 10.2337/diabetes.54.10.2911. [DOI] [PubMed] [Google Scholar]
- 17.Rasouli N, Kern PA. Adipocytokines and the metabolic complications of obesity. J Clin Endocrinol Metab. 2008;93(11 Suppl 1):S64–S73. doi: 10.1210/jc.2008-1613. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Garten A, Petzold S, Korner A, Imai S, Kiess W. Nampt: linking NAD biology, metabolism and cancer. Trends Endocrinol Metab. 2009;20(3):130–8. doi: 10.1016/j.tem.2008.10.004. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Lim SY, Davidson SM, Paramanathan AJ, Smith CC, Yellon DM, Hausenloy DJ. The novel adipocytokine visfatin exerts direct cardioprotective effects. J Cell Mol Med. 2008;12(4):1395–403. doi: 10.1111/j.1582-4934.2008.00332.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Hammarstedt A, Pihlajamaki J, Rotter SV, Gogg S, Jansson PA, Laakso M, et al. Visfatin is an adipokine, but it is not regulated by thiazolidinediones. J Clin Endocrinol Metab. 2006;91(3):1181–4. doi: 10.1210/jc.2005-1395. [DOI] [PubMed] [Google Scholar]
- 21.Pagano C, Pilon C, Olivieri M, Mason P, Fabris R, Serra R, et al. Reduced plasma visfatin/pre-B cell colony-enhancing factor in obesity is not related to insulin resistance in humans. J Clin Endocrinol Metab. 2006;91(8):3165–70. doi: 10.1210/jc.2006-0361. [DOI] [PubMed] [Google Scholar]
- 22.Alexiadou K, Kokkinos A, Liatis S, Perrea D, Katsilambros N, Tentolouris N. Differences in plasma apelin and visfatin levels between patients with type 1 diabetes mellitus and healthy subjects and response after acute hyperglycemia and insulin administration. Hormones (Athens) 2012;11(4):444–50. doi: 10.14310/horm.2002.1376. [DOI] [PubMed] [Google Scholar]
- 23.Haider DG, Schaller G, Kapiotis S, Maier C, Luger A, Wolzt M. The release of the adipocytokine visfatin is regulated by glucose and insulin. Diabetologia. 2006;49(8):1909–14. doi: 10.1007/s00125-006-0303-7. [DOI] [PubMed] [Google Scholar]
- 24.Sarraf-Zadegan N, Sadri G, Malek AH, Baghaei M, Mohammadi FN, Shahrokhi S, et al. Isfahan Healthy Heart Programme: a comprehensive integrated community-based programme for cardiovascular disease prevention and control. Design, methods and initial experience. Acta Cardiol. 2003;58(4):309–20. doi: 10.2143/AC.58.4.2005288. [DOI] [PubMed] [Google Scholar]
- 25.Fonarow GC, Watson KE. High-density lipoprotein cholesterol as a therapeutic target to reduce cardiovascular events. Am Heart J. 2004;147(6):939–41. doi: 10.1016/j.ahj.2004.01.014. [DOI] [PubMed] [Google Scholar]
- 26.Tatzber F, Griebenow S, Wonisch W, Winkler R. Dual method for the determination of peroxidase activity and total peroxides-iodide leads to a significant increase of peroxidase activity in human sera. Anal Biochem. 2003;316(2):147–53. doi: 10.1016/s0003-2697(02)00652-8. [DOI] [PubMed] [Google Scholar]
- 27.Zheng RD, Chen ZR, Chen JN, Lu YH, Chen J. Role of Body Mass Index, Waist-to-Height and Waist-to-Hip Ratio in Prediction of Nonalcoholic Fatty Liver Disease. Gastroenterol Res Pract. 2012;2012:362147. doi: 10.1155/2012/362147. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Vavrova L, Kodydkova J, Zeman M, Dusejovska M, Macasek J, Stankova B, et al. Altered activities of antioxidant enzymes in patients with metabolic syndrome. Obes Facts. 2013;6(1):39–47. doi: 10.1159/000348569. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Roberts CK, Sindhu KK. Oxidative stress and metabolic syndrome. Life Sci. 2009;84(21-22):705–12. doi: 10.1016/j.lfs.2009.02.026. [DOI] [PubMed] [Google Scholar]
- 30.Kowalska I, Straczkowski M, Nikolajuk A, Adamska A, Karczewska-Kupczewska M, Otziomek E, et al. Serum visfatin in relation to insulin resistance and markers of hyperandrogenism in lean and obese women with polycystic ovary syndrome. Hum Reprod. 2007;22(7):1824–9. doi: 10.1093/humrep/dem118. [DOI] [PubMed] [Google Scholar]
- 31.Kolsgaard ML, Wangensteen T, Brunborg C, Joner G, Holven KB, Halvorsen B, et al. Elevated visfatin levels in overweight and obese children and adolescents with metabolic syndrome. Scand J Clin Lab Invest. 2009;69(8):858–64. doi: 10.3109/00365510903348677. [DOI] [PubMed] [Google Scholar]
- 32.Esteghamati A, Morteza A, Zandieh A, Jafari S, Rezaee M, Nakhjavani M, et al. The value of visfatin in the prediction of metabolic syndrome: a multi-factorial analysis. J Cardiovasc Transl Res. 2012;5(4):541–6. doi: 10.1007/s12265-012-9373-8. [DOI] [PubMed] [Google Scholar]
- 33.Fukuhara A, Matsuda M, Nishizawa M, Segawa K, Tanaka M, Kishimoto K, et al. Visfatin: a protein secreted by visceral fat that mimics the effects of insulin. Science. 2005;307(5708):426–30. doi: 10.1126/science.1097243. [DOI] [PubMed] [Google Scholar]
- 34.Cekmez F, Cekmez Y, Pirgon O, Canpolat FE, Aydinoz S, Metin IO, et al. Evaluation of new adipocytokines and insulin resistance in adolescents with polycystic ovary syndrome. Eur Cytokine Netw. 2011;22(1):32–7. doi: 10.1684/ecn.2011.0279. [DOI] [PubMed] [Google Scholar]
- 35.Haider DG, Holzer G, Schaller G, Weghuber D, Widhalm K, Wagner O, et al. The adipokine visfatin is markedly elevated in obese children. J Pediatr Gastroenterol Nutr. 2006;43(4):548–9. doi: 10.1097/01.mpg.0000235749.50820.b3. [DOI] [PubMed] [Google Scholar]
- 36.Kaminska A, Kopczynska E, Bronisz A, Zmudzinska M, Bielinski M, Borkowska A, et al. An evaluation of visfatin levels in obese subjects. Endokrynol Pol. 2010;61(2):169–73. [PubMed] [Google Scholar]
- 37.Yen CH, Yang NC, Lee BJ, Lin JY, Hsia S, Lin PT. The antioxidant status and concentrations of coenzyme Q10 and vitamin E in metabolic syndrome. ScientificWorld Journal. 2013;2013:767968. doi: 10.1155/2013/767968. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 38.Penckofer S, Schwertz D, Florczak K. Oxidative stress and cardiovascular disease in type 2 diabetes: the role of antioxidants and pro-oxidants. J Cardiovasc Nurs. 2002;16(2):68–85. doi: 10.1097/00005082-200201000-00007. [DOI] [PubMed] [Google Scholar]
- 39.Karaouzene N, Merzouk H, Aribi M, Merzouk SA, Berrouiguet AY, Tessier C, et al. Effects of the association of aging and obesity on lipids, lipoproteins and oxidative stress biomarkers: a comparison of older with young men. Nutr Metab Cardiovasc Dis. 2011;21(10):792–9. doi: 10.1016/j.numecd.2010.02.007. [DOI] [PubMed] [Google Scholar]
- 40.Senti M, Tomas M, Vila J, Marrugat J, Elosua R, Sala J, et al. Relationship of age-related myocardial infarction risk and Gln/Arg 192 variants of the human paraoxonase1 gene: the REGICOR study. Atherosclerosis. 2001;156(2):443–9. doi: 10.1016/s0021-9150(00)00680-8. [DOI] [PubMed] [Google Scholar]
- 41.Mecocci P, Polidori MC, Troiano L, Cherubini A, Cecchetti R, Pini G, et al. Plasma antioxidants and longevity: a study on healthy centenarians. Free Radic Biol Med. 2000;28(8):1243–8. doi: 10.1016/s0891-5849(00)00246-x. [DOI] [PubMed] [Google Scholar]
- 42.Brousseau ME, Schaefer EJ, Wolfe ML, Bloedon LT, Digenio AG, Clark RW, et al. Effects of an inhibitor of cholesteryl ester transfer protein on HDL cholesterol. N Engl J Med. 2004;350(15):1505–15. doi: 10.1056/NEJMoa031766. [DOI] [PubMed] [Google Scholar]
- 43.Davidson MH, McKenney JM, Shear CL, Revkin JH. Efficacy and safety of torcetrapib, a novel cholesteryl ester transfer protein inhibitor, in individuals with below-average high-density lipoprotein cholesterol levels. J Am Coll Cardiol. 2006;48(9):1774–81. doi: 10.1016/j.jacc.2006.06.067. [DOI] [PubMed] [Google Scholar]
- 44.Chen CC, Li TC, Li CI, Liu CS, Lin WY, Wu MT, et al. The relationship between visfatin levels and anthropometric and metabolic parameters: association with cholesterol levels in women. Metabolism. 2007;56(9):1216–20. doi: 10.1016/j.metabol.2007.04.018. [DOI] [PubMed] [Google Scholar]
- 45.Chan TF, Chen YL, Lee CH, Chou FH, Wu LC, Jong SB, et al. Decreased plasma visfatin concentrations in women with gestational diabetes mellitus. J Soc Gynecol Investig. 2006;13(5):364–7. doi: 10.1016/j.jsgi.2006.04.007. [DOI] [PubMed] [Google Scholar]
- 46.Filippatos TD, Derdemezis CS, Kiortsis DN, Tselepis AD, Elisaf MS. Increased plasma levels of visfatin/pre-B cell colony-enhancing factor in obese and overweight patients with metabolic syndrome. J Endocrinol Invest. 2007;30(4):323–6. doi: 10.1007/BF03346300. [DOI] [PubMed] [Google Scholar]
- 47.Ansari JA, Bhandari U, Pillai KK, Haque SE. Effect of rosuvastatin on obesity-induced cardiac oxidative stress in Wistar rats--a preliminary study. Indian J Exp Biol. 2012;50(3):216–22. [PubMed] [Google Scholar]
- 48.Chen SJ, Yen CH, Huang YC, Lee BJ, Hsia S, Lin PT. Relationships between inflammation, adiponectin, and oxidative stress in metabolic syndrome. PLoS One. 2012;7(9):e45693. doi: 10.1371/journal.pone.0045693. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 49.Zhong M, Tan HW, Gong HP, Wang SF, Zhang Y, Zhang W. Increased serum visfatin in patients with metabolic syndrome and carotid atherosclerosis. Clin Endocrinol (Oxf) 2008;69(6):878–84. doi: 10.1111/j.1365-2265.2008.03248.x. [DOI] [PubMed] [Google Scholar]
- 50.Jian WX, Luo TH, Gu YY, Zhang HL, Zheng S, Dai M, et al. The visfatin gene is associated with glucose and lipid metabolism in a Chinese population. Diabet Med. 2006;23(9):967–73. doi: 10.1111/j.1464-5491.2006.01909.x. [DOI] [PubMed] [Google Scholar]
- 51.Nusken KD, Nusken E, Petrasch M, Rauh M, Dotsch J. Preanalytical influences on the measurement of visfatin by enzyme immuno assay. Clin Chim Acta. 2007;382(1-2):154–6. doi: 10.1016/j.cca.2007.04.004. [DOI] [PubMed] [Google Scholar]
- 52.Korner A, Garten A, Bluher M, Tauscher R, Kratzsch J, Kiess W. Molecular characteristics of serum visfatin and differential detection by immunoassays. J Clin Endocrinol Metab. 2007;92(12):4783–91. doi: 10.1210/jc.2007-1304. [DOI] [PubMed] [Google Scholar]