The roles of vaspin, chemerin, and omentin in the determination of metabolic syndrome

Background

In general, metabolic syndrome (MetS) is defined as a collection of multiple risk factors including abdominal obesity, dyslipidaemia, abnormal glycaemia, and elevated blood pressure [1]. Metabolic syndrome is also associated with an increased risk of type 2 diabetes, cardiovascular morbidity, and mortality [2–7]. Furthermore, there is an association between MetS and increased total cancer mortality [8, 9]. The incidence of metabolic syndrome and the pathophysiological mechanisms underlying its development are still not fully understood. It is believed that the occurrence of MetS arises from the complex relationship between genetic and environmental factors.
The aim of the study was to give an overview and summarise the current knowledge regarding genetic determinants of metabolic syndrome. The relationship between polymorphisms of the genes encoding selected adipokines (vaspin, chemerin and omentin) and the risk of MetS, as well as other metabolic disorders, was also analysed.

Heritability as a metabolic syndrome risk factor

Based on the results of a family study conducted in 2015, it was concluded that daughters whose mothers had MetS had a higher risk of an occurrence of this syndrome than children whose fathers were suffering from MetS [10]. On the other hand, in Teheran the population with the highest risk of an occurrence of MetS components was observed among families whose fathers and offspring had abdominal obesity, dyslipidaemia, abnormal glycaemia, or elevated blood pressure [11].
According to reports [10, 12, 13], in 24–32% of cases, MetS is inherited. It was also found that the percentage of heritability varies and is dependent on the number of MetS components.
Bellia et al. demonstrated that among MetS subtypes, a cluster of three components (central obesity, hypertriglyceridaemia, and a low level of HDL) had the highest heritability at 31% [13].
Results of MetS component analysis, based on the Northern Manhattan Family Study, obtained two independent factors: factor 1 – lipids/glucose/obesity, and factor 2 – blood pressure, of which heritability accounts for 44% and 20%, respectively [12]. Panizzon et al. demonstrated that in a group of siblings in Vietnam, two main MetS factors can be selected. It was shown that insulin resistance (glucose, insulin), lipids (HDL, triglycerides – TG), and adiposity (body mass index – BMI, waist circumference) share genetic influences, which accounts for factor 1. They also detected genetic influences that were mutual for both adiposity and blood pressure (factor 2), but not with lipids or insulin resistance [14].
Multiple studies confirm that adiposity is the sole component of MetS that is genetically related to all the others. Long-term observation indicates that a large waist circumference precedes the appearance of other MetS components. The researchers suggest that genetic predisposition to adiposity may steer overlapping pathophysiologies in MetS components [15].
However, the precise determination of the MetS genotype is difficult because metabolic syndrome occurrence is a combination of multiple risk factors. In recent years, research on the most likely genetic variants of MetS have been conducted using molecular biology and statistical methods like multiple candidate gene association studies, linkage studies, and genome-wide association studies (GWAS), all with ambiguous results. For example, based on the results of GWAS, conducted by Zabaneh and Balding, it can be established that there are no common genetic mechanisms explaining MetS occurrence [16].
Nevertheless, there are many studies confirming that several candidate gene polymorphisms are associated with a risk of MetS occurrence. All data on this are shown in Table 1 [17–31].
In 2011 Avery et al. identified three new pleiotropic loci associated with multiple metabolic trait domains: APOC1, BRAP, and PLCG1 [22]. In the same year Kraja et al. demonstrated that five single nucleotide polymorphisms (SNPs) were associated with MetS and are located within three locations: LPL, CETP, and APOA5 cluster (including BUD13, ZNF259, and APOA5); all of these selected genes play an important role in lipid metabolism [20]. In 2012 Kristiansson et al. identified only one gene, namely SNP (rs964184) of ZPR1, which is significantly associated with MetS. Other identified mutations were located in or near a lipid-related genetic loci APOA1/C3/A4/A5, APOB, LPL, and CETP. However, the association was significant only with the TG/HDL/WC factor, but none was associated with two or more individual uncorrelated MetS components [18]. Other studies show that two SNPs, rs17782312 in MC4R (involved in weight regulation) and rs2943634 IRS1 (related to insulin resistance), were associated with MetS [28]. In 2014 Hashemi et al. found that the insertion/deletion polymorphism of 45-bp in UCP2 gene was significantly associated with MetS. The authors demonstrate that the I (insertion) allele decreased the risk of MetS in comparison with the D (deletion) allele [31]. In the Korean population two polymorphisms located near BUD13 (rs11216126, rs180349) were significantly related to MetS [24]. On the other hand, this significance was not confirmed among the Chinese population [32]. Comparative analysis in the African-American population identified 27 SNPs associated with various components of MetS. Unfortunately, only one rs12721054 in APOC1 was associated with all five of the studied components of the syndrome [23]. In 2015, GWAS was carried out on the African population identifying three mutations near RALYL, KSR2, and MBNL1 associated with MetS, and another two near CA10 and CTNNA3. The last two were specific to the African ancestry population [25]. In recent years Mirhafez et al. identified another SNP rs964184 in ZPR1, which was associated with MetS [33]. Lin et al. showed an association of MetS at the genome-wide significance level with two SNPs: rs16944558/COLEC12 and rs662799/APOA5 [21].
Although there are many reports describing the relation of gene variants and individual MetS components, there are only a few evaluating the most likely genetic basis of the syndrome.

Adipokines

In recent years, adipose tissue has become a main subject of intensive research. It was found that this tissue is not only limited to an energy storage function, but it is also an active endocrine organ. Numerous compounds demonstrating hormonal properties, produced and secreted by adipocytes, have been identified – all defined as adipokines. The metabolic role of adipokines is varied – appetite regulation, maintaining energy balance, regulation of fat and carbohydrate metabolism, influence on insulin action, as well as adipose tissue remodelling – to name a few. It has been shown that adipokines are involved in angiogenesis and vascular remodelling, also in the formation of atherosclerotic plaque, as well as in the regulation of blood pressure and modulation of inflammatory and immunological processes. The number of newly discovered adipokines increases each year, three being particularly studied in the context of MetS.
Vaspin (SERPINA12) was first identified from visceral adipose tissue of a rat model with type 2 diabetes [34]. Initially, vaspin was classified as a member of the serpine (serine protease inhibitors) family, which was confirmed in 2013 based on a crystal structure [35]. The core structure consists of three-sheets and nine-helices. It was also shown that the reactive centre loop (RCL) is flexible and located between G364 and P381. Unfortunately, the mechanism of action was not established, but it was shown that the most likely target for vaspin is the kallikrein-related peptidase 7 (hK7) [35, 36]. The physiological functions of the vaspin target are diverse. The main role of kallikrein is the proteolysis of intercellular cohesive structures that precede desquamation, the shedding of the outermost layer of the epidermis. In recent years, an overexpression of hK7 was linked with ovarian, breast, and testicular cancer. An interesting fact is that the vaspin–hK7 system is linked to obesity-associated skin diseases such as psoriasis. It was also reported that vaspin exhibits glucose lowering effects. The mechanism of glucose level regulation is based on increasing the half-life of insulin rather than improving insulin-mediated glucose uptake [35, 37].
Several studies reported higher vaspin concentrations in adult women compared with men [38–40], whereas others did not [41]. Körner et al. showed that gender differences arise during pubertal progression in girls and are not present in pre-pubertal children. It was also observed that vaspin increased with puberty in girls, but not in boys [42]. Xu et al. reported that plasma vaspin increased with aging in both males and females, but to a lesser extent in males [43]. Plasma vaspin levels were increased in both the midcycle and the luteal phases compared to the follicular phase in women, these increases being proportional to the changes in oestrogen and 17-OH progesterone levels [44]. As it was shown, the vaspin concentration was varied and dependent on many physiological factors.
Various positive associations between a serum vaspin concentration and obesity indicators have been demonstrated [38, 41, 45–50]. The most significant was observed between vaspin concentration and the percentage of body fat [45]. In 2014 Feng et al. conducted a meta-analysis based on databases of Medline, PubMed, and EMBASE. It was found that the level of vaspin was 0.52 ng/ml higher (p < 0.05) in obese subjects than in non-obese healthy control subjects [48]. Liu et al. demonstrated that vaspin is able to promote the differentiation of 3T3-L1 preadipocytes and may increase their sensitivity to insulin and suppress obesity [51]. Choi et al. also noted positive correlations between plasma vaspin concentrations and body mass index, waist circumference, and percentage of body fat – but only in men [52]. Farmazi et al. showed that training for 12 weeks (three sessions per week, 1 h per session) in overweight women (BMI > 25 kg/m²) had a significant effect on the decrease of BMI (p < 0.05), waist circumference (WC) (p < 0.05), body fat (p = 0.05), and vaspin (p < 0.05) [53]. On the other hand, Auguet et al. and Sperling et al. stated that there is no correlation between vaspin concentration and obesity [54, 55].
A new approach was presented by Wada in 2008. Based on in vivo studies, it was shown that an injection of recombinant vaspin in subject mice improved glucose tolerance and increased insulin sensitivity [56]. Many researchers suggest that this increased expression of vaspin genes plays an important compensatory role in obesity and insulin resistance [57, 58]. An interesting observation was demonstrated in the independent research of Ataya et al. and Feng et al. Considering the duration of diabetes, the negative correlation between time and vaspin concentration was shown [48, 59]. Based on these results, Dimova et al. suggested that vaspin plays a compensative role in glucose metabolism disorders at the outset of type 2 diabetes (T2DM), and its secretion capacity gradually declines with the increase of the diabetes duration [60]. However, the results of studies conducted on humans are ambiguous. Most of them did not show increased levels of vaspin in patients with diabetes [38, 58, 61–63]. Moreover, some of the results showed decreased vaspin concentrations in patients with diabetes [64, 65]. The investigation into the relation of the vaspin variant and type 2 diabetes show that the AA genotype of vaspin rs2236242 confers an increased risk of type 2 diabetes when compared with the TT genotype. Patients who were homozygous for the rs2236242 A allele had a 2.33-fold increased risk of type 2 diabetes [66]. Hida et al. confirmed that, in vivo, serum vaspin levels are elevated in individuals with impaired fasting glucose or impaired glucose tolerance and type 2 diabetes. Vaspin levels did not correlate with HOMA or insulin levels; however, they correlated with fasting plasma glucose, suggesting a role in glucose metabolism, particularly in the fasting state [39]. The previously mentioned research by Feng et al., based on meta-analysis, demonstrated that the level of vaspin is 0.36 ng/ml higher in patients with type 2 diabetes compared with the control subjects [48]. Two years of prospective studies confirmed that a low serum concentration of vaspin is a risk factor for the progression of type 2 diabetes. The authors have shown that decreased baseline serum vaspin is an independent risk factor for the subsequent occurrence of diabetes in non-diabetic subjects and a higher risk for insulin treatment in diabetic patients [67]. The most recent results conducted by Abdel Ghany et al. in 2017 described the novel, protective role of vaspin variant in obesity. The minor A allele of vaspin rs2236242 polymorphism plays a protective role against obesity and diabetes, but this association is largely ascribed to its effect on insulin resistance [68].
As mentioned before, there are many associations between vaspin and various physiological and pathophysiological processes. It has been shown that an increased vaspin concentration is related to polycystic ovary syndrome (PCOS) [45, 69]. Moreover, Serum vaspin levels reflect the severity of polycystic ovary syndrome [69]. Kohan et al. suggest that allele A of vaspin rs2236242 gene polymorphism decreases the risk of PCOS compared to the T allele. This relation was not shown to be statistically significant after adjusting genotypes for BMI. It was suggested that this relationship is affected by obesity status [70]. A relationship between the plasma vaspin concentration and the presence of coronary artery disease was also observed [71, 72]. Choi et al. demonstrate that vaspin concentrations are associated with the presence and severity of coronary atherosclerosis, but only in female patients [52]. Some results suggest that vaspin cannot be used as an independent marker for the presence of coronary artery disease in the general population. However, recent results have confirmed that the vaspin level is associated with the presence of coronary artery disease in patients with type 2 diabetes [58, 73].
Another correlation was observed between vaspin concentration and the limitation of endothelial cell apoptosis caused by free fatty acids [74]. It was also implied that vaspin alleviates the dysfunction of endothelial progenitor cells induced by high glucose [75]. It can be assumed that vaspin indirectly affects many metabolic functions, which may be crucial in the development of MetS.
According to many authors, the exact relationship between many metabolic disorders, such as obesity, diabetes, polycystic ovary syndrome, and coronary artery disease, and vaspin has become a potential biomarker for metabolic syndrome.
In the earliest analysis of reports from 2011, it was shown that plasma vaspin concentrations were significantly higher in men with metabolic syndrome (Me = 0.60 ng/ml) compared with those without MetS (Me = 0.40 ng/ml). These relationships were not found in women [52]. Esteghamati et al. detected elevated vaspin levels in the presence of MetS in both genders and assigned vaspin as a predictor for MetS. Moreover, vaspin was found to be the most significant predictor for reduced HDL-cholesterol and raised waist circumference, fasting plasma glucose, and triglycerides, after controlling for age in both sexes [76]. Karbek et al. confirmed that serum vaspin levels are significantly higher in patients with MetS than age-matched control subjects [77]. In 2016, Alnory et al. analysed vaspin concentrations in Egyptian women with MetS and in control subjects. Significantly higher serum levels of vaspin were observed in patients with MetS (3.34 ±0.52 ng/ml) in comparison to non-MetS cases (1.87 ±0.54 ng/ml). The researchers concluded that serum vaspin concentrations can be used as diagnostic markers of metabolic syndrome [78]. Other researchers have demonstrated that non-alcoholic fatty liver disease and related entities, found in as many as 90% of subjects with MetS, have also been associated with an elevated levels of serum vaspin [79]. Based on research conducted on obese patients (BMI ≥ 30 kg/m²), Mirzaei et al. noted that the concentration of vaspin is significantly higher in participants with MetS compared to non-MetS subjects [80]. In 2014 Lu et al. came to the same conclusion after an examination of patients undergoing bariatric surgery (BMI ≥ 40 or BMI ≥ 35 kg/m² with associated comorbidities). There were significant associations of high vaspin levels with glucose and lipid-related metabolic parameters in severely obese patients, as well as post-operative increases in vaspin levels, and correlations of higher pre- and postoperative vaspin concentrations with better metabolic profile [81]. Studies carried out on the Caucasian population demonstrate no overt fluctuations in vaspin levels in the early stages of glucose intolerance and MetS [60]. Opposing results were previously reported by Kim et al. The authors demonstrated that serum vaspin concentration was significantly lower in men with MetS than in men without MetS. This research was conducted on the Korean population. It was shown that serum vaspin levels tended to decrease with an increasing number of metabolic syndrome components, and was negatively correlated with waist circumference, serum triglyceride level, and systolic and diastolic blood pressure, but positively correlated with HDL-cholesterol level. However, after adjusting for sex, this correlation disappeared [40]. Auguet et al. reported that serum vaspin levels were not increased in morbidly obese women (BMI ≥ 40 kg/m²) and that they did not correlate with BMI and markers of glucose or lipid metabolism [54]. Amouzad Mahdirejei et al. demonstrated that serum vaspin levels do not correlate with anthropometric and metabolic parameters, and an 8-week resistance training programme significantly improved the insulin resistance index. However, this form of exercise failed to result in significant changes in serum vaspin concentration and lipid profiles [82].
A new approach considers the association of vaspin variants and MetS prevalence. Hashemi et al. demonstrated that genotype frequencies of vaspin rs2236242 were significantly different between subjects with and without MetS, in both genders. The minor allele frequency (A allele) of rs2236242 polymorphism in subjects with and without MetS was 0.334 and 0.490, respectively. In patients carrying the A allele, the risk of MetS was found to be significantly lower (OR = 0.52 (0.37–0.72)). Furthermore, it was shown that vaspin rs2236242 polymorphism was resistant against MetS in dominant, codominant, and recessive tested inheritance models, and the associations remained almost unchanged after adjusting for age and gender [83]. In the Egyptian population of woman, Mahanna confirmed that the minor A allele of vaspin rs2236242 polymorphism plays a protective role against MetS (OR = 1.973 (1.227–3.171)). The carriers of vaspin rs2236242 TA and AA genotypes also significantly decreased BMI, waist circumference, systolic and diastolic blood pressures, fasting blood glucose (FBG), fasting serum insulin, insulin resistance, TG, total cholesterol (TC), and LDL-C and increased HDL-C compared with the carriers of the TT genotype [84]. Opposing results were published by Alnory et al. They showed no significant difference in the allele and genotype frequency of vaspin rs2236242 polymorphism between the MetS and non-MetS groups. In addition, no significant difference in the vaspin levels between different polymorphic forms of vaspin rs2236242 was detected [78].
Chemerin is also known as tazarotene-induced gene 2 (TIG2) or retinoic acid receptor response protein 2 (RARRES2). The gene encoding preprochemerin (RARRES2) is located on 7q36.1 in humans. Interestingly, chemerin is mainly produced in the liver and adipose tissue, but it is also expressed in many other locations including the adrenal glands, placenta, pancreas, lungs, and skin [85].
It has been shown that chemerin has been secreted as an inactive precursor, prochemerin, which is an amino acid 143. Proteolytic processing of the C-terminus of prochemerin is required for this protein to become an active chemoattractant [86]. Recently, many isoforms of chemerin have been identified in various tissues. It is already known that chemerin is a multifunctional protein due to the significance of receptors. Chemerin is primarily identified as the natural ligand of chemokine-like receptor 1 (CMKLR1), which is expressed on several immune cell subsets, such as plasmacytoid dendritic cells, macrophages, and natural killer cells [87]. Therefore the response to chemerin arises through chemotaxis or the modulation of their defence function. In recent years, new functions of chemerin have been discovered, linking this protein with metabolism regulation. Chemerin is an adipocyte signalling molecule important in adipogenesis, and it also plays a role in angiogenesis, osteoblastogenesis, myogenesis, and in regulating glucose homeostasis [85, 88].
There are many studies which evaluate the correlation between chemerin levels and gender, producing ambiguous results. Stejskal et al. found no statistically significant difference in chemerin levels between men and women [89]. Bozaoglu et al. and Lehrke et al. noted higher chemerin levels in older individuals compared with younger individuals. Significant differences were observed in females compared with males, amounting to 188.5 ±65.3 and 168.2 ±55.7 ng/ml, respectively [90–92].
The same studies carried out on the Chinese population showed different dependencies. Chemerin levels were significantly higher in male than in female subjects [93]. Landgraf et al. demonstrated that in a group of non-obese and healthy children (age 7–18 years), chemerin serum concentrations showed a negative correlation with age (r = –0.31) and pubertal stage (r = –0.24). There was a significant decrease in serum chemerin concentrations between prepubertal, pubertal, and postpubertal boys, but not girls [94]. Differences in chemerin concentration were also present in correlation with physiological stages in woman. The concentrations of chemerin were lower in peri- and premenopausal women (median = 118.0 ng/ml (99.2–135.0)), compared with postmenopausal women (median = 140.0 ng/ml (121.0–167.0)) [95].
There is an increasingly prominent premise that chemerin is involved in the pathophysiology of several metabolic and non-metabolic disorders. It has been reported that chemerin concentrations were significantly higher in obese compared to lean children and correlated with obesity-related parameters such as BMI SD score, leptin, and skinfold thickness [94]. It was also shown that in adults, chemerin levels were significantly associated with measures of body fat (weight, BMI, waist/hip ratio (WHR), fat mass – mainly visceral) [90, 96–98] and with adipocyte volume [99]. Cătoi et al. demonstrate that serum levels of chemerin were increased in morbidly obese men and women (74.20 ng/ml (58.31–116.90)) when compared with normal weight, healthy control subjects (25.45 ng/ml (19.75–30.10)) [100]. According to Bozaoglu et al., plasma chemerin levels could be a stimulator of angiogenesis. This function of chemerin suggests a role in the development of obesity through the promotion of angiogenesis within the expanding adipose tissue mass [101]. Additionally, partial correlation analyses showed that the serum chemerin was positively correlated with waist circumference and WHR, but not with BMI [102]. However, Stejskal et al. demonstrated that after adjustments for age and gender, chemerin levels were not corelated with fat indicators (BMI, WC) [89]. Research conducted by Sell et al. showed that the average chemerin concentration was significantly higher in women with severe obesity (BMI > 50.0 kg/m²) in comparison with healthy woman (p < 0.001). The concentration amounted to 353.8 ±18.0 ng/ml and 191.0 ±14.0 ng/ml, respectively. Chemerin levels were re-examined 1 year after the subjects’ bariatric operation, which induced the weight loss. Serum chemerin concentrations decreased significantly to an average value of 253.0 ±14.9 ng/ml, and after 2 years a greater decrease was observed [103]. Similar research was conducted by Ress et al. Eighteen months after bariatric surgery a significant decrease of serum chemerin concentrations was observed (175.91 ±24.5 ng/ml before surgery and 145.53 ±26.44 ng/ml after surgery) [104]. Chakaroun et al. investigated the chemerin level variation in three groups of obese subjects after three types of intervention – including 12 weeks of exercise, six months of calorie-restricted diet, and bariatric surgery. All interventions led to significantly reduced serum chemerin concentrations. There are many reports demonstrating that after diversified training, serum chemerin levels decreased in overweight or obese individuals [53, 105–107].
In many reports, it is also suggested that chemerin participates in the regulation of carbohydrate metabolism, and its serum levels correlate with fasting blood glucose, fasting insulin, HOMA-IR, glycated haemoglobin (HbA1c), independently of age and BMI [103, 108–111]. However, the relationship between chemerin and diabetes remains controversial. Increased levels of chemerin that occur with obesity are hypothesised to be a causal factor in the development of type 2 diabetes as a consequence of the dysregulation of the key physiological processes regulated by this adipokine [112]. Many researchers report that serum chemerin levels are significantly elevated in individuals with diabetes [99, 108, 109, 111, 113]. Fatima et al. suggest that chemerin may serve as a potential screening marker in the diagnosis of diabetes or predicting the risk of the development of diabetes in asymptomatic individuals [110]. According to Bozaoglu et al. and Weigert et al., plasma chemerin levels were not significantly different between subjects with type 2 diabetes and normal control subjects [90, 91, 114]. Moreover, Gateva et al., in the latest research, detected no significant differences between subjects with prediabetes (impaired fasting glucose and/or impaired glucose tolerance) and obese subjects with normoglycaemia [115]. Takahashi et al. established that there is a significant difference in chemerin concentration in patients with diabetes (164.9 ±6.3 ng/ml) compared with control subjects (218.7 ±7.3 ng/ml). It was also reported that fasting glucose levels were negatively associated with serum chemerin levels – but only in male subjects [93]. Controversial results were also obtained after a comparison of serum chemerin levels in pregnant women with gestational diabetes and healthy pregnant women [116, 117].
Weigert et al. showed that serum chemerin concentration was elevated in T2DM subjects with higher CRP levels (> 5 ng/ml) and positively correlated with CRP in normal-weight, overweight, and T2DM subjects, after adjusting for BMI and WC. The authors proposed that systemic chemerin levels are related to inflammation rather than obesity in T2DM subjects [114]. Serum chemerin levels were significantly higher in the group with coronary artery disease (CAD), in comparison with those who did not have CAD [118–121]. In addition, serum chemerin concentration was correlated with the severity of the disease [119]. Although significantly high serum chemerin levels were found in CAD, it is not known if this increased level represents a predictor for CAD or if it is a result of atherosclerotic plaque morphology [92, 122]. Hart et al. reported that chemerin stimulates the adhesion of macrophages to extracellular matrix protein fibronectin and vascular cell adhesion molecule 1 (VCAM-1). This process has been proposed to contribute to the progression of atherosclerosis [123]. Prospective studies demonstrate that there is a strong positive association between chemerin concentrations at baseline and risk of heart failure. Participants in the fourth quartile of chemerin had more than four-times higher a risk of heart failure [124]. According to Aydin et al., chemerin was not found to be an independent risk factor for predicting atherosclerosis in diabetes and prediabetes [125]. Ebert et al. demonstrated that chemerin, showing the strongest association with MetS components in the general population, suggests that adverse adipose tissue function is a major contributor to these metabolic abnormalities [126].
Lehrke et al. found that chemerin is associated with markers of inflammation and components of metabolic syndrome, but does not predict coronary atherosclerosis [92]. On the other hand, Aronis et al. were not able to show chemerin as a predictor of acute coronary syndrome [127]. Some studies showed a significant increase of chemerin level in non-alcoholic fatty liver disease (NAFLD) patients [128, 129]. It was implied that this increase is connected with obesity [130]. The ambiguous results of a met-analysis conducted in 2016 did not confirm the relationship between chemerin and NAFLD [131]. Increased serum chemerin in women with PCOS, with or without obesity, suggest that chemerin may be involved in the development of the pathogenesis of PCOS [132]. It has also been shown that there is no significant association between chemerin rs17173608 gene polymorphism and PCOS, after adjusting genotypes for BMI; notedly, this relationship was affected by obesity status [133]. An interesting result was published by Adrych et al. According to the authors, there is an association between chronic pancreatitis in humans and an increased serum chemerin concentration [134]. It can also be concluded that chemerin may also be a distinctive regulator of blood pressure because of its significant (high) correlation with diastolic pressure [110]. This effect of chemerin on blood pressure may also be related to its high expression by the kidneys, which is the primary regulator of blood pressure [89].
Numerous studies have demonstrated the relationship between chemerin and MetS components, including triglycerides, HDL-cholesterol, and blood pressure [89, 90, 92, 135–137]. In 2008, Stejskal et al. determined that serum chemerin levels correlated with a number of metabolic syndrome risk factors (r = 0.47) [89]. However, a meta-analysis consisting of eight studies (1787 patients) demonstrated that among six MetS components, only WC and TG were positively correlated with chemerin concentration [97]. From a number of reports analysing the correlation between serum chemerin concentration and MetS as a whole, no individual components demonstrate that the level of serum chemerin was significantly elevated in MetS patients compared to healthy control subjects [102, 118, 138, 139]. It was shown that after adjustments for body fat percentage, the chemerin concentration was 3.0 ng/ml higher in those with metabolic syndrome than in those without [140]. In a study of Caucasian individuals, at a serum chemerin cut-off level of 240 μg/l, the presence of metabolic syndrome was diagnosed with 75% sensitivity and 67% specificity [89]. A meta-analysis of GWAS combined with mRNA expression studies in three independent cohorts from Europe highlighted the role of genetic variation in the RARRES2 locus in the regulation of circulating chemerin concentrations [141]. Analysis of RARES2 expression demonstrate a strong association with MetS (p = 1.9 × 10–5) and with the individual components of MetS: waist circumference (p = 1.6 × 10–8), HDL (p = 2.0 × 10–5), and diastolic blood pressure (p = 1.5 × 10–4) [142]. Hashemi et al. observed a positive association between chemerin rs17173608 polymorphism and the risk of MetS. The minor allele frequency (G allele) of rs17173608 polymorphism in subjects with and without MetS was 0.21 and 0.13, respectively. The risk of MetS occurrence significantly increases in patients carrying the G allele (OR = 1.78, 95% CI: 1.14–2.75, p = 0.021). According to the authors, chemerin rs17173608 polymorphism increases the risk of MetS in codominant and dominant tested inheritance models (OR = 2.13, 95% CI: 1.23–3.70, p = 0.007, TT vs. TG; and OR = 2.03, 95% CI: 1.22–3.40, p = 0.007, TT vs. TG-GG, respectively) [83]. Mehanna et al. confirmed that in Egyptian females, the minor G allele of the chemerin rs17173608 polymorphism had a significantly higher frequency in metabolic syndrome patients than in the control subjects (OR = 0.351, 95% CI: 0.198–0.625, p = 0.0001), and the frequencies of TG and GG genotypes were significantly higher in metabolic syndrome patients (OR = 0.320, 95% CI: 0.166–0.619, p = 0.0001). The carriers of the G allele in the homozygous and heterozygous forms (GG and TG genotypes) also showed significantly higher BMI, waist circumference, systolic and diastolic blood pressures, fasting blood glucose, fasting serum insulin, insulin resistance, triglycerides, and total and LDL cholesterol, and lower HDL-cholesterol, compared with the carriers of the TT genotype [84].
Omentin, also known as intelectin 1 (ITLN1), was described in 2003 as a new adipokine secreted from omental adipose tissue. ITLN1 is coded by two genes (1 and 2) from which corresponding isoforms are formed. The arising mRNA is primarily expressed in the stromal vascular fraction. The final hydrophilic protein contains 313 amino acids (35 kDa) in which a secretory signal sequence and a fibrinogen-related domain can be distinguished. The role of omentin is not fully understood, but it is likely that ITLN1 enhances insulin-mediated glucose uptake in adipocytes and activates protein kinase Akt/PKB [143]. Based on the latest research, it can be assumed that omentin takes part in the connection between many organs and in the regulation of many physiological and pathological processes. There is a supposition that omentin inhibits TNF--induced cyclooxygenase-2 (COX-2) expression via pathway AMPK active (eNOS)/NO, which inhibits Jun N-terminal kinase (JNK) signalling, and following this, acts as an anti-inflammatory in endothelial cells. As a consequence of the activation of eNOS/NO path, vasodilation occurs in isolated blood vessels and decreases the agonist-induced increase in blood pressure [144, 145]. Moreover, the omentin-induced AMPK phosphorylation can reduce the RAS/ERK signalling cascade. These actions can be accompanied by the reduction of cardiac hypertrophy and smooth muscle cell (SMC) proliferation [146].
In 2014, Kataoka et al. established that omentin can promote the AMPK/AKT pathway directly by suppressing myocyte apoptosis in acute ischaemic heart injury, and can decrease the expression of proinflammatory mediators, including TNF, IL-6, and the monocyte chemotactic protein-1 (MCP-1) in macrophages [143]. In 2011, Duan et al. proposed that omentin inhibited osteoblastic differentiation of CVSMCs through the PI3K/Akt signalling pathway. It was also suggested that the lower omentin levels in obese (especially in visceral obese) subjects contribute to the development of arterial calcification, with omentin playing a protective role against arterial calcification [147].
It was also suggested that omentin inhibited NOX/p38/HSP27 pathways to prevent platelet-derived growth factor (PDGF-BB)-induced smooth muscle cell (SMC) migration. These may be related to the protective role of omentin in neointimal hyperplasia [148]. However, specific receptors for omentin have not yet been identified.
Major parts of these reports demonstrate that serum omentin-1 concentration is higher in the case of females in comparison with males [149, 150]. Opposing results were published by Moreno-Navarette et al. [151]. Lesná et al. and Vu et al. claimed that there is no significant difference between omentin concentrations in males and females [152, 153]. Until now, there have been no reports demonstrating a correlation between serum omentin-1 and age.
It was previously shown that baseline and post-weight loss omentin-1 concentration were significantly higher in obese men than women, and averaged 48.1 ±8.3 vs. 40.3 ±8.6 ng/ml in baseline serum, respectively, and 56.4 ±8.7 vs. 49.5 ±8.03 ng/ml in post-weight loss serum, respectively [151]. Tan et al. demonstrated that the expression of ITLN1 mRNA in adipose tissue and serum concentration of omentin-1 were negatively corelated with 17-oestradiol [154]. According to Luque-Ramirez et al., gender, BMI, and free testosterone explained 48% of variability of ITLN1 values in the areas under the oral glucose tolerance rest curve [155]. Numerous reports show that serum omentin-1 was lower in obese than in lean individuals and negatively correlated with body weight, weight gain, BMI, waist and hip circumferences, fat mass, and visceral fat area [54, 100, 149–151, 156, 157]. Additionally, in morbidly obese subjects, omentin-1 levels were decreased when compared with normal-weight healthy subjects [100, 158]. Furthermore, it was demonstrated that omentin-1 probably plays an protective role in obesity-related inflammation [100, 159]. A study conducted on a population of pregnant women demonstrate that pre-existing maternal obesity is associated with lower omentin-1 expression in the placenta, adipose tissue, and maternal plasma [160]. Opposing results were obtained in 2017 by Montazerifar et al. According to these authors, serum omentin-1 levels did not correlate with BMI, whereas a negative correlation was found between serum omentin-1 and waist circumference, suggesting that BMI is a weaker surrogate for body fat distribution than WC [161]. As previously mentioned, there are no reports establishing a correlation between serum omentin and age. However, it has been shown that in children and adolescents, likewise in adults, serum omentin-1 is lower in the obese than in the lean [162–164]. Furthermore, Oświęcimska et al. reported that the mean serum omentin concentration in girls with anorexia nervosa (46.1 ±3.8 ng/ml) was statistically significantly higher than that of healthy (34.3 ±2.6 ng/ml) and obese girls (30.7 ±2.5 ng/ml)[163]. Hamnvik et al. found that omentin-1 does not display any day-night variation and that omentin-1 levels remain unaltered in both chronic and acute energy deprivation [165]. Recent findings by Nway et al. suggest that omentin may also be involved in the regulation of appetite. Omentin expression correlated with neuropeptide Y expression in both types of adipose tissue [166]. It was also proposed that omentin-1 variants may be important in obesity. However, Splichal et al. identified that polymorphism Val109Asp in the omentin gene did not differ in genotype distribution and/or allele frequency between the obese and non-obese cohorts. Nevertheless, there were significant differences in genotype distributions of rs2274907 Val109Asp polymorphism in the omentin gene between the obese and morbidly obese cohorts. It was also found that the TT genotype of rs2274907 polymorphism was associated with the lowest (7877 ±2780 J/day) and the AA genotype with the highest (8764 ±2467 J/day) energy intake [167]. In the Kyrgyz population, significant associations between Val109Asp polymorphism in omentin gene and abdominal obesity was noted. An increased risk of abdominal obesity was associated with homozygous genotype Val109Val. Frequencies of Asp109Asp, Val109Asp, and Val109Val genotypes among individuals with abdominal obesity (48, 40, and 12%, respectively) were different from those among control subjects (Asp109Asp – 53%, Val109Asp – 43%, and Val109Val – 4%) [168]. Saremi et al. examined the effects of 12 weeks of aerobic training on serum omentin-1 concentrations [169]. Omentin-1 concentration was significantly increased after the aerobic programme and correlated with changes in waist circumference, insulin resistance, glucose concentration, and aerobic fitness. Ouergh et al. found an increase in plasma omentin levels following an 8-week high-intensity interval training in both overweight/obese and normal-weight untrained young men [170]. Wilms et al. showed a strong relationship between exercise performance and circulating omentin-1 levels as well as an increase of the adipokine in response to a 6-week endurance training programme in obese women [171]. A 16-week exercise training programme resulted in a significant increase in serum omentin-1 concentrations in obese children. The authors suggest that exercise-induced changes in omentin-1 may be associated with the beneficial effects of exercise on reduced insulin and weight loss [172]. Numerous research papers show that omentin concentration was inversely correlated with glucose metabolism markers [54, 113, 150, 173]. In Caucasians, the correlation between ITLN1 gene variants and type 2 diabetes occurrence was not identified [174]. El-Mesallamy et al. observed significantly reduced serum omentin-1 concentration in type 2 diabetes patients (19.7 ±1.0 ng/ml), compared with healthy control subjects (27.4 ±2.6 ng/ml) [113]. Akour et al., in a cross-sectional study, found lower omentin-1 concentrations in plasma in pre- or diabetic obese patients compared to normoglycaemic subjects [175]. It is thought that omentin-1 levels are closely associated with the endogenous insulin reserve [176]. Serum and vitreous omentin-1 levels in patients with proliferative diabetic retinopathy were markedly decreased compared with those without diabetic retinopathy, with non-proliferative diabetic retinopathy, and with the healthy control subjects [177]. Meta-analysis conducted by Tang et al. suggested that circulating omentin-1 levels are significantly lower in women with polycystic ovary syndrome compared with control subjects, which indicates that omentin-1 may play a role in the pathologic processes of polycystic ovary syndrome [178]. In analysing obstructive sleep apnoea syndrome, it was found that the omentin serum levels were low [179, 180]. The same results were obtained after analysing serum omentin levels in inflammatory diseases [148, 181]. It has also been suggested that omentin-1 rs2274907 polymorphism might be a candidate genetic factor for susceptibility to nonalcoholic fatty liver disease [70]. However, according to Wittenbecher et al., despite inverse associations of omentin-1 with measures of body fat, no indication of a diabetes protective role of omentin-1 was found in prospective analyses [182]. In studies conducted on patients in the range of 62–81 years of age, the correlation between higher serum levels of omentin-1 and increases in fasting glucose, 2-h glucose, HbA1c, and with incident type 2 diabetes, were significant [183]. Research conducted by Yilmaz et al. demonstrate that omentin levels were elevated in nonalcoholic fatty liver disease, which is a medical condition co-occurring with obesity and diabetes, although obesity and diabetes are associated with low concentrations of omentin [184]. According to Montazerifar, there is no significant difference between serum omentin level between nonalcoholic fatty liver disease patients and control subjects [161]. Wang considers that these contradictory results may indicate an adaptation response [158].
In recent findings, Harada et al. demonstrated that plasma omentin levels were lower in patients with coronary artery disease compared with control subjects (343 ±158 ng/ml vs. 751 ±579 ng/ml) and were negatively associated with the expression of omentin in epicardial adipose tissue in patients with coronary artery disease. There was no significant difference between patients with coronary artery disease and control subjects regarding omentin Val109Asp polymorphism [185]. However, a 2.5-fold increase in Val/Val genotype was detected in subjects with coronary artery disease [186]. The results of Jamshidi et al. indicate that the Asp allele of Val109Asp (T allele of rs2274907) is more frequent among men with coronary artery disease than among healthy men [187]. In the Pakistani population, individuals having Val/Asp heterozygous genotype of omentin-1 gene polymorphism are at higher risk of developing coronary artery disease in comparison to Asp/Asp and Val/Val genotypes [188].
In most reports, the analysis was based only on the correlation between serum omentin concentration and MetS components. Less often the analysis considered omentin and MetS as a syndrome.
Shibata et al. reported that circulating omentin-1 levels were inversely correlated with the number of metabolic risks, such as increased waist circumference, dyslipidaemia, high blood pressure, and glucose intolerance. This was found in a study done on Japanese men who were taking no medications [189]. Liu et al. show that omentin-1 is closely related to MetS and might play an important role in atherosclerosis in MetS patients [190]. It was also reported that omentin-1 was negatively associated with waist circumference, systolic blood pressure, and fasting blood glucose. However, a significant difference was observed between men with metabolic syndrome, who had 20% lower plasma omentin-1 levels, and women with metabolic syndrome [153].
Circulating levels of omentin-1 were useful predictors of metabolic health status in overweight and obese individuals, but no association was seen between omentin-1 and metabolic health status in normal-weight subjects [191]. Jialal et al. reported that plasma levels of omentin-1 were 41% lower in patients with nascent MetS as compared with control subjects [137]. Moreover, omentin was associated with high-density lipoprotein cholesterol and inversely with triglycerides and glucose. Opposing results were found by Vu et al. According to these authors, plasma omentin-1 concentrations did not differ significantly between individuals with and without MetS (145.7 ±70 ng/ml vs. 157.4 ±79.3 ng/ml, p > 0.05) [153]. However, men with metabolic syndrome had significantly lower omentin-1 levels than men without metabolic syndrome (129.9 ±66 ng/ml vs. 186.3 ±84.3 ng/ml, p = 0.03). Plasma omentin-1 concentrations were significantly correlated with HDL cholesterol in the entire study cohort (r = 0.26; p = 0.01), which was primarily driven by a correlation in men (r = 0.451, p = 0.002) and participants with metabolic syndrome (r = 0.36; p = 0.003). In the female population, there were no significant differences between plasma omentin-1 concentrations and metabolic parameters [192]. In prepubertal children (age 7 ±1 years), increased circulating omentin-1 was associated with a poorer metabolic profile, with higher fasting triglycerides and blood pressure, and familial prevalence of diabetes. In studies conducted by Kilic et al., the plasma omentin concentration was similar in non-diabetic MetS patients and healthy control subjects, although the plasma omentin levels were correlated with high triglyceride and low high-density lipoprotein-cholesterol levels [193]. In an obese group of children, the omentin-1 level was negatively correlated with BMI, insulin, HOMA-IR, and WC, while no significant correlation was observed with systolic blood pressure (SBP), diastolic blood pressure (DBP), and triglyceride levels [162]. In obese children (12–17 years old), serum omentin-1 levels were significantly lower in the MetS group compared to the group without MetS (289.5 ±51.9 ng/ml vs. 268.2 ±60 ng/ml) [194]. To the best of our knowledge, there are no reports regarding omentin variants in MetS.

Conclusions

The adipokines that have been described in this paper significantly influence human metabolic homeostasis. However, current research sometimes presents ambiguous results. Consequently, precise evaluation of their role in the pathogenesis of some metabolic diseases, including the pathogenesis of MetS, is difficult. Further studies are necessary in order to determine whether the increased vaspin serum concentration observed in obese people is due to a compensation mechanism to increased insulin sensitivity, and if vaspin concentration could be a biomarker for insulin resistance. Similarly, it should be clarified if the increased concentration of chemerin accompanying obesity and type 2 diabetes is associated with the visceral fat accumulation in obese patients or with chronic inflammation. It would also be indispensable to study the association between ITLN1 polymorphisms and MetS prevalence. Furthermore, studies on the identification of omentin receptors are essential, as well as an evaluation of omentin concentration fluctuations depending on age.
A thorough understanding the pathomechanisms of MetS, involving vaspin, chemerin, and omentin, may in the future allow us to use these adipokines as potential biomarkers of metabolic disorder risk. Those adipokines may also be vital to extend pharmacological strategies of metabolic disease treatment.

Conflict of interest

The authors declare no conflict of interest.

References

1. Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, Fruchart JC, James WP, Loria CM, Smith SC Jr; International Diabetes Federation Task Force on Epidemiology and Prevention; Hational Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; International Association for the Study of Obesity. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 2009; 120: 1640-1645.
2. Lakka HM. The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA 2002; 288: 2709-2716.
3. Wang J, Ruotsalainen S, Moilanen L, Lepisto P, Laakso M, Kuusisto J. The metabolic syndrome predicts cardiovascular mortality: a 13-year follow-up study in elderly non-diabetic Finns. Eur Heart J 2007; 28: 857-864.
4. Aggarwal A, Aggarwal S, Sharma V. Cardiovascular risk factors in young patients of coronary artery disease: differences over a decade. J Cardiovasc Thorac Res 2014; 6: 169-173.
5. Abbasalizad M, Jahangiry L, Asghari-jafarabadi M, Najafi M. Association between dietary patterns and metabolic syndrome in a sample of Tehranian adults. Obesity Res Clin Pract 2016; 10 (Suppl 1): S64-73.
6. Majda A, Zalewska-Puchała J, Kamińska A, Bodys-Cupak I, Suder M. Risk factors for diseases of the cardiovascular system among Catholics living in areas of southern Poland. Medical Studies 2017; 33: 88-94.
7. Sadowski M, Janion-Sadowska A. The management of patients with cardiogenic shock. Medical Studies 2017; 33: 55-62.
8. Gathirua-Mwangi WG, Monahan PO, Murage MJ, Zhang J. Metabolic syndrome and total cancer mortality in the Third National Health and Nutrition Examination Survey. Cancer Causes Control 2017; 28: 127-136.
9. Kozłowska-Geller M. Mechanisms of carcinogenesis in colorectal cancer. Medical Studies 2017; 33: 308-315.
10. Khan RJ, Gebreab SY, Sims M, Riestra P, Xu R, Davis SK. Prevalence, associated factors and heritabilities of metabolic syndrome and its individual components in African Americans: the Jackson Heart Study. BMJ Open 2015; 5: e008675.
11. Zarkesh M, Asghari G, Amiri P, Hosseinzadeh N, Hedayati M, Ghanbarian A. Familial aggregation of metabolic syndrome with different socio-behavioral characteristics: the fourth phase of Tehran Lipid and Glucose Study. Iran Red Crescent Med J 2016; 18: e30104.
12. Lin HF, Boden-Albala B, Juo SH, Park N, Rundek T, Sacco RL. Heritabilities of the metabolic syndrome and its components in the Northern Manhattan Family Study. Diabetologia 2005; 48: 2006-2012.
13. Bellia A, Giardina E, Lauro D, Tesauro M, Fede G Di, Cusumano G, Federici M, Rini GB, Novelli G, Laurao R, Sbraccia P. “The Linosa Study’”: epidemiological and heritability data of the metabolic syndrome in a Caucasian genetic isolate. Nutrition Metabolism Cardiovasc Dis 2009; 19: 455-461.
14. Panizzon MS, Hauger RL, Sailors M, Lyons MJ, Jacobson KC, Murray RE, Rana B, Vasilopoulos T, Vuoksimaa E, Xian H, Kremen WS, Franz CE. A new look at the genetic and environmental coherence of metabolic syndrome components. Obesity 2015; 23: 2499-2507.
15. Cameron A. The metabolic syndrome: validity and utility of clinical definitions for cardiovascular disease and diabetes risk prediction. Maturitas 2010; 65: 117-121.
16. Zabaneh D, Balding DJ. A genome-wide association study of the metabolic syndrome in Indian Asian men. PLoS One 2010; 5: e11961.
17. Xi B, Ruiter R, Chen J, Pan H, Wang Y, Mi J. The ACE insertion/deletion polymorphism and its association with metabolic syndrome. Metabolism 2012; 61: 891-897.
18. Kristiansson K, Perola M, Tikkanen E, Kettunen J, Surakka I, Havulinna AS, Stancáková A, Barnes C, Widen E, Kajantie E, Eriksson JG, Viikari J, Kähönen M, Lehtimäki T, Raitakari OT, Hartikainen AL, Ruokonen A, Pouta A, Jula A, Kangas AJ, Soininen P, Ala-Korpela M, Männistö S, Jousilahti P, Bonnycastle LL, Järvelin MR, Kuusisto J, Collins FS, Laakso M, Hurles ME, Palotie A, Peltonen L, Ripatti S, Salomaa V. Genome-wide screen for metabolic syndrome susceptibility loci reveals strong lipid gene contribution but no evidence for common genetic basis for clustering of metabolic syndrome traits. Circulation Cardiovasc Genet 2012; 5: 242-249.
19. Povel CM, Boer JMA, Reiling E, Feskens EJM. Genetic variants and the metabolic syndrome: a systematic review. Obes Rev 2011; 12: 952-967.
20. Kraja AT, Vaidya D, Pankow JS, Goodarzi MO, Assimes TL, Kullo IJ, Sovio U, Mathias RA, Sun YV, Franceschini N, Absher D, Li G, Zhang Q, Feitosa MF, Glazer NL, Haritunians T, Hartikainen AL, Knowles JW, North KE, Iribarren C, Kral B, Yanek L, O’Reilly PF, McCarthy MI, Jaquish C, Couper DJ, Chakravarti A, Psaty BM, Becker LC, Province MA, Boerwinkle E, Quertermous T, Palotie L, Jarvelin MR, Becker DM, Kardia SL, Rotter JI, Chen YD, Borecki IB. A bivariate genome-wide approach to metabolic syndrome: STAMPEED Consortium. Diabetes 2011; 60: 1329-1339.
21. Lin E, Kuo P, Liu Y, Yang AC, Tsai S. Detection of susceptibility loci on APOA5 and COLEC12 associated with metabolic syndrome using a genome-wide association study in a Taiwanese population. Oncotarget 2017; 8: 93349-93359.
22. Avery CL, He Q, North KE, Ambite JL, Boerwinkle E, Fornage M. A phenomics-based strategy identifies loci on APOC1, BRAP, and PLCG1 associated with metabolic syndrome phenotype domains. PLoS Genet 2011; 7: e1002322.
23. Carty CL, Bhattacharjee S, Haessler J, Al E. Comparative analysis of metabolic syndrome components in over 15,000 African Americans identifies pleiotropic variants: results from the PAGE Study. Circ Cardiovasc Genet 2014; 7: 505-513.
24. Jeong SW, Chung M, Park S, Cho SB, Hong K. Genome-wide association study of metabolic syndrome in Koreans. Genom Informatics 2014; 12: 187-194.
25. Tekola-Ayele F, Doumatey AP, Shriner D, Bentley AR, Chen G, Zhou J, Fasanmade O, Johnson T, Oli J, Okafor G,Eghan BA Jr, Agyenim-Boateng K, Adebamowo C, Amoah A, Acheampong J, Adeyemo A, Rotimi CN. Genome-wide association study identifies African-ancestry specific variants for metabolic syndrome. Mol Genet Metab 2015; 116: 305-313.
26. Zhang L, Dai Y, Bian L, Wang W, Wang W, Muramatsu M, Hua Q. Association of the cell death-inducing DNA fragmentation factor alpha-like effector A (CIDEA) gene V115F (G/T) polymorphism with phenotypes of metabolic syndrome in a Chinese population. Diabetes Res Clin Pract 2011; 91: 233-238.
27. Ghattas MH, Mehanna ET, Mesbah NM, Abo-elmatty DM. Association of estrogen receptor alpha gene polymorphisms with metabolic syndrome in Egyptian women. Metabolism 2013; 62: 1437-1442.
28. Povel CM, Boer JM, Onland-Moret N, Dollé ME, Feskens EJ, van der Schouw YT. Single nucleotide polymorphisms (SNPs) involved in insulin resistance, weight regulation, lipid metabolism and inflammation in relation to metabolic syndrome: an epidemiological study. Cardiovasc Diabetol 2012; 11: 133.
29. Kordi-Tamandani DM, Hashemi M, Sharifi N, Kaykhaei MA, Torkamanzehi A. Association between paraoxonase-1 gene polymorphisms and risk of metabolic syndrome. Mol Biol Rep 2012; 39: 937-943.
30. Gupta V, Gupta A, Jafar T, Gupta V, Agrawal S, Srivastava N, Kumar S, Singh AK, Natu SM, Agarwal CG, Agarwal GG. Association of TNF-promoter gene G-308A polymorphism with metabolic syndrome, insulin resistance, serum TNF- and leptin levels in Indian adult women. Cytokine 2012; 57: 32-36.
31. Hashemi M, Rezaei H, Kaykhaei M, Taheri M. A 45-bp insertion/deletion polymorphism of UCP2 gene is associated with metabolic syndrome. J Diab Metab Disord 2014; 13: 12.
32. Zhang L, You Y, Wu Y, Zhang Y, Wang M, Song Y, Liu X, Kou C. Association of BUD13 polymorphisms with metabolic syndrome in Chinese population: a case-control study. Lipids Health Disease 2017; 16: 127.
33. Mirhafez SR, Avan A, Pasdar A, Khatamianfar S, Hosseinzadeh L, Ganjali S, Movahedi A, Pirhoushiaran M, Gómez Mellado V, Rosace D, van Krieken A, Nohtani M, Ferns GA, Ghayour-Mobarhan M. Zinc finger 259 gene polymorphism rs964184 is associated with serum triglyceride levels and metabolic syndrome. Int J Mol Cell Med 2016; 5: 8-18.
34. Hida K, Wada J, Eguchi J, Zhang H, Baba M, Seida A, Hashimoto I, Okada T, Yasuhara A, Nakatsuka A, Shikata K, Hourai S, Futami J, Watanabe E, Matsuki Y, Hiramatsu R, Akagi S, Makino H, Kanwar YS. Visceral adipose tissue-derived serine protease inhibitor: a unique insulin-sensitizing adipocytokine in obesity. Proc Natl Acad Sci 2005; 102: 10610-10615.
35. Heiker JT, Klöting N, Kovacs P, Kuettner EB, Sträter N, Schultz S, Kern M, Stumvoll M, Blüher M, Beck-Sickinger AG. Vaspin inhibits kallikrein 7 by serpin mechanism. Cell Mol Life Sci 2013; 70: 2569-2583.
36. Schleinitz D. Genetic determination of serum levels of diabetes-associated adipokines. Rev Diab Stud 2015; 12: 277-298.
37. Dimova R, Tankova T. The role of vaspin in the development of metabolic and glucose tolerance disorders and atherosclerosis. BioMed Res Int 2015; 2015: 823481.
38. Youn BS, Kloting N, Kratzsch J, Lee N, Park JW, Song ES, Ruschke K, Oberbach A, Fasshauer M, Stumvoll M, Blüher M. Serum vaspin concentrations in human obesity and type 2 diabetes. Diabetes 2008; 57: 372-377.
39. Hida K, Poulsen P, Teshigawara S, Nilsson E, Friedrichsen M, Ribel-Madsen R, Grunnet L, Lund SS, Wada J, Vaag A. Impact of circulating vaspin levels on metabolic variables in elderly twins. Diabetologia 2012; 55: 530-532.
40. Kim JM, Kim TN, Won JC. Association between serum vaspin level and metabolic syndrome in healthy Korean subjects. Metab Syndr Relat Disord 2013; 11: 385-391.
41. Chang HM, Patk HS, Song YS, Jang YJJ. Association between serum vaspin concentrations and visceral adipose tissue in Korean subjects. Metab Clin Exp 2010; 59: 1276-1281.
42. Körner A, Neef M, Friebe D, Erbs S, Kratzsch J, Dittrich K, Blüher S, Kapellen TM, Kovacs P, Stumvoll M, Blüher M, Kiess W. Vaspin is related to gender, puberty and deteriorating insulin sensitivity in children. Int J Obes 2011; 35: 578-586.
43. Xu X, Wen J, Lu Y, Ji H, Zhuang J, Su Y, Liu B, Li H, Xu Y. Impact of age on plasma vaspin concentration in a group of normal Chinese people. J Endocrinol Investig 2017; 40: 143-151.
44. Wyskida K, Franik G, Wikarek T, Owczarek A, Delroba A, Chudek J, Sikora J, Olszanecka-Glinianowicz M. The levels of adipokines in relation to hormonal changes during the menstrual cycle in young, normal-weight women. Endocr Connect 2017; 6: 892-900.
45. Tan BK, Heutling D, Chen J, Farhatullah S, Adya R, Keay SD, Kennedy CR, Lehnert H, Randeva HS. Metformin decreases the adipokine vaspin in overweight women with polycystic ovary syndrome concomitant with improvement in insulin sensitivity and a decrease in insulin resistance. Diabetes 2008; 57: 1501-1507.
46. Suleymanoglu S, Tascilar E, Pirgon O, Tapan S, Meral C, Abaci A. Vaspin and its correlation with insulin sensitivity indices in obese children. Diab Res Clin Pract 2009; 84: 325-328.
47. Bluher M. Vaspin in obesity and diabetes: pathophysiological and clinical significance. Endocrine 2012; 41: 176-182.
48. Feng R, Li Y, Wang C, Luo C, Liu L. Higher vaspin levels in subjects with obesity and type 2 diabetes mellitus: a meta-analysis. Diab Res Clin Pract 2014; 106: 88-94.
49. Saboori S, Hosseinzadeh-attar MJ, Yousefi E, Hosseini M. The comparison of serum vaspin and visfatin concentrations in obese and normal weight women. Diabetes Metab Syndr Clin Res Rev 2015; 9: 320-323.
50. Yang W, Li Y, Tian T, Wang L. Serum vaspin concentration in elderly type 2 diabetes mellitus patients with differing body mass index: a cross-sectional study. BioMed Res Int 2017; 2017: 4875026.
51. Liu P, Li G, Wu J, Zhou X, Wang L, Han W, Lv Y, Sun C. Vaspin promotes 3T3-L1 preadipocyte differentiation. Exp Biol Med 2015; 240: 1520-1527.
52. Choi SH, Kwak SH, Lee Y, Moon MK, Lim S, Park YJ, Jang HC, Kim MS. Plasma vaspin concentrations are elevated in metabolic syndrome in men and are correlated with coronary atherosclerosis in women. Clin Endocr 2011; 75: 628-635.
53. Faramarzi M, Banitalebi E, Nori S, Farzin S, Taghavian Z. Effects of rhythmic aerobic exercise plus core stability training on serum omentin, chemerin and vaspin levels and insulin resistance of overweight women. J Sports Med Phys Fitness 2016; 56: 476-482.
54. Auguet T, Quintero Y, Riesco D, Morancho B, Terra X, Crescenti A, Broch M, Aguilar C, Olona M, Porras JA, Hernandez M, Sabench F, del Castillo D, Richart C. New adipokines vaspin and omentin. Circulating levels and gene expression in adipose tissue from morbidly obese women. BMC Med Genet 2011; 12: 60.
55. Sperling M, Grzelak T, Pelczyńska M, Jasinska P, Bogdanski P, Pupek-Musialik D, Czyzewska K. Concentrations of omentin and vaspin versus insulin resistance in obese individuals. Biomed Pharmacother 2016; 83: 542-547.
56. Wada J. Vaspin: a novel serpin with insulin-sensitizing effects. Exp Opinon Investig Drugs 2008; 17: 327-333.
57. Klöting N, Berndt J, Kralisch S, Kovacs P, Fasshauer M, Schön MR, Stumvoll M, Blüher M. Vaspin gene expression in human adipose tissue: Association with obesity and type 2 diabetes. Biochem Biophys Res Commun 2006; 339: 430-436.
58. Yang W, Li Y, Tian T, Wang L, Lee P, Hua Q. Serum vaspin concentration in elderly patients with type 2 diabetes mellitus and macrovascular complications. BMC Endocr Disord 2017; 17: 67.
59. Atya H, Hassan Z, Amin A, Al E. Vaspin concentration in obesity, impaired glucose tolerance and type 2 diabetes in Egypt. Adv Res Biol Sci 2013; 1: 6-13.
60. Dimova R, Tankova T, Kirilov G, Chakarova N, Dakov-ska L, Grozeva G. Is vaspin related to cardio‑metabolic status and autonomic function in early stages of glucose intolerance and in metabolic syndrome? Diabetol Metab Syndr 2016; 8: 46.
61. Li K, Li L, Yang M, Liu H, Liu D, Yang H, Boden G, Yang G. Short-term continuous subcutaneous insulin infusion decreases the plasma vaspin levels in patients with type 2 diabetes mellitus concomitant with improvement in insulin sensitivity. Eur J Endocrinol 2011; 164: 905-910.
62. Ye Y, Hou X, Pan X, Lu J, Jia W. Serum vaspin level in relation to postprandial plasma glucose concentration in subjects with diabetes. Chin Med J 2009; 122: 2530-2533.
63. Bilir BE, Guldiken S, Tuncbilek N, Demir AM, Polat A. The effects of fat distribution and some adipokines on insulin resistance in subjects with prediabetes. Endokrynol Pol 2016; 67: 277-282.
64. Gulcelik NE, Karakaya J, Gedik A, Usman A, Gurlek A. Serum vaspin levels in type 2 diabetic women in relation to microvascular complications. Eur J Endocrinol 2009; 160: 65-70.
65. Jian W, Peng W, Xiao S, Li H, Jin J, Qin L, Dong Y, Su Q. Role of serum vaspin in progression of type 2 diabetes: a 2-year cohort study. PLoS One 2014; 9: e94763.
66. Kempf K, Rose B, Illig T, Rathmann W, Strassburger K, Thorand B, Meisinger C, Wichmann HE, Herder C, Vollmet C. Vaspin (SERPINA12) genotypes and risk of type 2 diabetes: results from the MONICA/KORA studies. Exp Clin Endocrinol Diab 2010; 118: 184-189.
67. Yan T, Li L, Wang H, Wang J, Cai D. Correlation between adipocytokines levels and metabolic syndrome in type 2 diabetes mellitus. J South Med Univ 2014; 34: 275-278.
68. Abdel Ghany SM, Sayed AA, El-deek SEM, Elbadre HM, Dahpy MA, Saleh MA, Sharaf El-Deen H, Mustafa MH. Obesity risk prediction among women of Upper Egypt: the impact of serum vaspin and vaspin rs2236242 gene polymorphism. Gene 2017; 626: 140-148.
69. Koiou E, Dinas K, Tziomalos K, Toulis K, Kandaraki EA, Kalaitzakis E, Katsikis I, Panidis D. The phenotypes of polycystic ovary syndrome defined by the 1990 diagnostic criteria are associated with higher serum vaspin levels than the phenotypes introduced by the 2003 criteria. Obesity Facts 2011; 4: 145-150.
70. Kohan L, Zarei A, Fallahi S, Tabiee O. Association between vaspin rs2236242 gene polymorphism and polycystic ovary syndrome risk. Gene 2014; 539: 209-212.
71. Aust G, Richter O, Rohm S, Kerner C, Hauss J, Klöting N, Ruschke K, Kovacs P, Youn BS, Blüher M. Vaspin serum concentrations in patients with carotid stenosis. Atherosclerosis 2009; 204: 262-266.
72. Kadoglou NPE, Gkontopoulos A, Kapelouzou A, Fotiadis G, Theofilogiannakos EK, Kottas G, Lampropoulos S. Serum levels of vaspin and visfatin in patients with coronary artery disease – Kozani study. Clin Chim Acta 2011; 412: 48-52.
73. Hao F, Zhang H, Zhu J, Kuang H, Yu Q, Bai M, Mu J. Association between vaspin level and coronary artery disease in patients with type 2 diabetes. Diabetes Res Clin Pract 2016; 113: 26-32.
74. Jung CH, Lee WJ, Hwang JY, Seol SM, Kim YM, Lee YL, Park JY. Vaspin protects vascular endothelial cells against free fatty acid-induced apoptosis through a phosphatidylinositol 3-kinase/Akt pathway. Biochem Biophys Res Commun 2011; 413: 264-269.
75. Sun N, Wang H, Wang L. Vaspin alleviates dysfunction of endothelial progenitor cells induced by high glucose via PI3K/Akt/eNOS pathway. Int J Clin Exp Pathol 2015; 8: 482-489.
76. Esteghamati A, Noshad S, Mousavizadeh M, Zandieh A, Nakhjavani M. Association of vaspin with metabolic syndrome: the pivotal role of insulin resistance. Diabetes Metab J 2014; 38: 143-149.
77. Karbek B, Bozkurt NC, Topaloglu O, Aslan MS, Gungunes A, Cakal E, Delibasi T. Relationship of vaspin and apelin levels with insulin resistance and atherosclerosis in metabolic syndrome. Minerva Endocrinol 2014; 39: 99-105.
78. Alnory A, Gad H, Hegazy G, Shaker O. The association of vaspin rs2236242 and leptin rs7799039 polymorphism with metabolic syndrome in Egyptian women. Turk J Med Sci 2016; 46: 1335-1340.
79. Aktas B, Yilmaz Y, Eren F, Yonal O, Kurt R. Serum levels of vaspin, obestatin, and apelin-36 in patients with nonalcoholic fatty liver disease. Metab Clin Exp 2011; 60: 544-549.
80. Mirzaei K, Hossein-nezhad A, Keshavarz S, Koohdani F, Saboor-Yaraghi AA, Hosseini S, Eshraghian MR, Djalali M. Crosstalk between circulating peroxisome proliferator-activated receptor gamma, adipokines and metabolic syndrome in obese subjects. Diabetol Metab Syndr 2013; 5: 79.
81. Lu H, Wamba PCF, Lapointe M, Poirier P, Martin J, Bastien M, Cianflone K. Increased vaspin levels are associated with beneficial metabolic outcome pre- and post-bariatric surgery. PLoS One 2014; 9: e111002.
82. Amouzad Mahdirejei H, Fadaei Reyhan Abadei S, Abbaspour Seidi A, Eshaghei Gorji N, Rahmani Kafshgari H, Ebrahim Pour M, Bagheri Khalili H, Hajeizad F, Khayeri M. Effects of an eight-week resistance training on plasma vaspin concentrations, metabolic parameters levels and physical fitness in patients with type 2 diabetes. Cell J 2014; 16: 367-374.
83. Hashemi M, Rezaei H, Eskandari-Nasab E, Kaykhaei MA, Zakeri Z, Taheri M. Association between chemerin rs17173608 and vaspin rs2236242 gene polymorphisms and the metabolic syndrome, a preliminary report. Gene 2012; 510: 113-117.
84. Mehanna ET, Mesbah NM, Ghattas MH, Saleh SM, Abo-Elmatty DM. Association of chemerin Rs17173608 and vaspin Rs2236242 gene polymorphisms with metabolic syndrome in Egyptian women. Endocr Res 2016; 41: 43-48.
85. Bondue B, Wittamer V, Parmentier M. Chemerin and its receptors in leukocyte trafficking, inflammation and metabolism. Cytokine Growth Factor Rev 2011; 22: 331-338.
86. Mattern A, Zellmann T, Beck-Sickinger AG. Processing, signaling, and physiological function of chemerin. IUBMB Life 2014; 66: 19-26.
87. De Henau O, Degroot G, Imbault V, Robert V, De Poorter C, Mcheik S, Galés C, Parmentier M, Springael JY. Signaling properties of chemerin receptors CMKLR1, GPR1 and CCRL2. PLoS One 2016; 11: e0164179.
88. Banas M, Zabieglo K, Kasetty G, Kapinska-Mrowiecka M, Borowczyk J, Drukala J, Murzyn K, Zabel BA, Butcher EC, Schroeder JM, Schmidtchen A, Cichy J. Chemerin is an antimicrobial agent in human epidermis. PLoS One 2013; 8: e58709.
89. Stejskal D, Karpisek M, Hanulova Z, Svestak M. Chemerin is an independent marker of the metabolic syndrome in a Caucasian population – a pilot study. Biomed Pap Med Fac Univ Palacky Olomouc Czech Republic 2008; 152: 217-221.
90. Bozaoglu K, Bolton K, McMillan J, Zimmet P, Jowett J, Collier G, Walder K, Segal D. Chemerin is a novel adipokine associated with obesity and metabolic syndrome. Endocrinology 2007; 148: 4687-4694.
91. Bozaoglu K, Segal D, Shields KA, Cummings N, Curran JE, Comuzzie AG, Mahaney MC, Rainwater DL, VandeBerg JL, MacCluer JW, Collier G, Blangero J, Walder K, Jowett JB. Chemerin is associated with metabolic syndrome phenotypes in a Mexican-American population. J Clin Endocr Metab 2009; 94: 3085-3088.
92. Lehrke M, Becker A, Greif M, Stark R, Laubender RP, von Ziegler F, Lebherz C, Tittus J, Reiser M, Becker C, Göke B, Leber AW, Parhofer KG, Broedl UC. Chemerin is associated with markers of inflammation and components of the metabolic syndrome but does not predict coronary atherosclerosis. Eur J Endocrinol 2009; 161: 339-344.
93. Takahashi M, Inomata S, Okimura Y, Iguchi G, Fukuoka H, Miyake K, Koga D, Akamatsu S, Kasuga M, Takahashi Y. Decreased serum chemerin levels in male Japanese patients with type 2 diabetes: sex dimorphism. Endocr J 2013; 60: 37-44.
94. Landgraf K, Friebe D, Ullrich T, Kratzsch J, Dittrich K, Herberth G, Adams V, Kiess W, Erbs S, Körner A. Chemerin as a mediator between obesity and vascular inflammation in children. J Clin Endocr Metab 2012; 97: E556-E564.
95. Menzel J, Biemann R, Aleksandrova K, Schulze MB, Boeing H, Isermann B, Weikert C. The cross-sectional association between chemerin and bone health in peri/pre and postmenopausal women: results from the EPIC-Potsdam study. Menopause 2018; 25: 574-578.
96. Pfau D, Bachmann A, Lossner U, Kratzsch J, Bluher M, Stumvoll M, Fasshauer M. Serum levels of the adipokine chemerin in relation to renal function. Diabetes Care 2010; 33: 171-173.
97. 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: e113915.
98. Cheon DY, Kang JG, Lee SJ, Ihm SH, Lee EJ, Choi MG, Yoo HJ, Kim CS. Serum chemerin levels area associated with visceral adiposity, independent of waist circumference, in newly diagnosed type 2 diabetic subjects. Yonsei Med J 2017; 58: 319.
99. Andersson DP, Laurencikiene J, Acosta JR, Rydén M, Arner P. Circulating and adipose levels of adipokines associated with insulin sensitivity in nonobese subjects with type 2 diabetes. J Clin Endocrinol Metab 2016; 101: 3765-3771.
100. Cătoi AF, Suciu Ş, Pârvu AE, Copăescu C, Galea RF, Buzoianu AD, Vereşiu IA, Cătoi C, Pop ID. Increased chemerin and decreased omentin-1 levels in morbidly obese patients are correlated with insulin resistance, oxidative stress and chronic inflammation. Clujul Med 2014; 87: 19-26.
101. Bozaoglu K, Curran JE, Stocker CJ, Zaibi MS, Segal D, Konstantopoulos N, Morrison S, Carless M, Dyer TD, Cole SA, Goring HH, Moses EK, Walder K, Cawthorne MA, Blangero J, Jowett JB. Chemerin, a novel adipokine in the regulation of angiogenesis. J Clin Endocrinol Metabol 2010; 95: 2476-2485.
102. Wang D, Yuan GY, Wang XZ, Jia J, Di LL, Yang L, Chen X, Qian FF, Chen JJ. Plasma chemerin level in metabolic syndrome. Genet Mol Res 2013; 12: 5986-5991.
103. Sell H, Divoux A, Poitou C, Basdevant A, Bouillot J, Bedossa P, Tordjman J, Eckel J, Clément K. Chemerin correlates with markers for fatty liver in morbidly obese patients and strongly decreases after weight loss induced by bariatric surgery. J Clin Endocrinol Metabol 2010; 95: 2892-2896.
104. Ress C, Tschoner A, Engl J, Klaus A, Tilg H, Ebenbichler CF, Patsch JR, Kaser S. Effect of bariatric surgery on circulating chemerin levels. Eur J Clin Investig 2010; 40: 277-280.
105. Kim SH, Lee SH, Ahn KY, Lee DH, Suh YJ, Cho SG, Choi YJ, Lee DH, Lee SY, Hong SB, Kim YS, Jeon JY, Nam M. Effect of lifestyle modification on serum chemerin concentration and its association with insulin sensitivity in overweight and obese adults with type 2 diabetes. Clin Endocrinol 2014; 80: 825-833.
106. Stefanov T, Blüher M, Vekova A, Bonova I, Tzvetkov S, Kurktschiev D, Temelkova-Kurktschiev T. Circulating chemerin decreases in response to a combined strength and endurance training. Endocrine 2014; 45: 382-391.
107. Liu M, Lin X, Wang X. Decrease in serum chemerin through aerobic exercise plus dieting and its association with mitigation of cardio-metabolic risk in obese female adolescents. J Pediatr Endocrinol Metabol 2018; 31: 127-135.
108. Tönjes A, Fasshauer M, Kratzsch J, Stumvoll M, Blüher M. Adipokine pattern in subjects with impaired fasting glucose and impaired glucose tolerance in comparison to normal glucose tolerance and diabetes. PLoS One 2010; 5: e13911.
109. Yang M, Yang G, Dong J, Liu Y, Zong H, Liu H, Boden G, Li L. Elevated plasma levels of chemerin in newly diagnosed type 2 diabetes mellitus with hypertension. J Investig Med 2010; 58: 883-886.
110. 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: e57113.
111. Habib SS, Eshki A, AlTassan B, Fatani D, Helmi H, AlSaif S. Relationship of serum novel adipokine chemerin levels with body composition, insulin resistance, dyslipidemia and diabesity in Saudi women. Eur Rev Med Pharmacol Sci 2017; 21: 1296-1302.
112. Roman AA, Parlee SD, Sinal CJ. Chemerin: a potential endocrine link between obesity and type 2 diabetes. Endocrine 2012; 42: 243-251.
113. El-Mesallamy HO, El-Derany MO, Hamdy NM. Serum omentin-1 and chemerin levels are interrelated in patients with Type 2 diabetes mellitus with or without ischaemic heart disease. Diab Med 2011; 28: 1194-1200.
114. Weigert J, Neumeier M, Wanninger J, Filarsky M, Bauer S, Wiest R, Farkas S, Scherer MN, Schäffler A, Aslanidis C, Schölmerich J, Buechler C. Systemic chemerin is related to inflammation rather than obesity in type 2 diabetes. Clin Endocrinol 2010; 72: 342-348.
115. Gateva A, Assyov Y, Tsakova A, Kamenov Z. Classical (adiponectin, leptin, resistin) and new (chemerin, vaspin, omentin) adipocytokines in patients with prediabetes. Horm Mol Biol Clin Investig 2018. doi:10.1515/hmbci-2017-0031.
116. Gorkem U, Kucukler FK, Togrul C, Gungor T. Are adipokines associated with gestational diabetes mellitus? J Turk Germ Gynecol Assoc 2016; 17: 186-190.
117. Fatima SS, Alam F, Chaudhry B, Khan TA. Elevated levels of chemerin, leptin, and interleukin-18 in gestational diabetes mellitus. J Matern Fetal Neonatal Med 2017; 30: 1023-1028.
118. Dong B, Ji W, Zhang Y. Elevated serum chemerin levels are associated with the presence of coronary artery disease in patients with metabolic syndrome. Intern Med 2011; 50: 1093-1097.
119. Yan Q, Zhang Y, Hong J, Gu W, Dai M, Shi J, Zhai Y, Wang W, Li X, Ning G. The association of serum chemerin level with risk of coronary artery disease in Chinese adults. Endocrine 2012; 41: 281-288.
120. Motawi TMK, Mahdy SG, El-Sawalhi MM, Ali EN, El-Telbany RFA. Serum levels of chemerin, apelin, vaspin, and omentin-1 in obese type 2 diabetic Egyptian patients with coronary artery stenosis. Can J Physiol Pharmacol 2018; 96: 38-44.
121. Xiaotao L, Xiaoxia Z, Yue X, Liye W. Serum chemerin levels are associated with the presence and extent of coronary artery disease. Coron Artery Dis 2012; 23: 412-416.
122. Hah Y, Kim NK, Kim MK, Kim HS, Hur S, Yoon H, Kim YN, Park KG. Relationship between chemerin levels and cardiometabolic parameters and degree of coronary stenosis in Korean patients with coronary artery disease. Diabetes Metab J 2011; 35: 248-254.
123. Hart R, Greaves DR. Chemerin contributes to inflammation by promoting macrophage adhesion to VCAM-1 and fibronectin through clustering of VLA-4 and VLA-5. J Immunol 2010; 185: 3728-3739.
124. Menzel J, di Giuseppe R, Biemann R, Wittenbecher C, Aleksandrova K, Eichelmann F, Fritsche A, Schulze MB, Boeing H, Isermann B, Weikert C. Association between chemerin, omentin-1 and risk of heart failure in the population-based EPIC-Potsdam study. Sci Rep 2017; 7: 14171.
125. Aydin K, Canpolat U, Akin S, Dural M, Karakaya J, Aytemir K, Özer N, Gürlek A. Chemerin is not associated with subclinical atherosclerosis markers in prediabetes and diabetes. Anatol J Cardiol 2015; 16: 749-755.
126. Ebert T, Gebhardt C, Scholz M, Wohland T, Schleinitz D, Fasshauer M, Blüher M, Stumvoll M, Kovacs P, Tönjes A. Relationship between 12 adipocytokines and distinct components of the metabolic syndrome. J Clin Endocrinol Metabol 2018; 103: 1015-1023.
127. Aronis KN, Sahin-efe A, Chamberland JP, Iii AS, Vokonas P, Mantzoros CS. Chemerin levels as predictor of acute coronary events: a case–control study nested within the veterans affairs normative aging study. Metabolism 2014; 63: 760-766.
128. Zhuang X, Sun F, Li L, Jiang D, Li X, Sun A, Pan Z, Lou N, Zhang L, Lou F. Therapeutic effect of metformin on chemerin in non-obese patients with non-alcoholic fatty liver disease (NAFLD). Clin Labor 2015; 61: 1409-1414.
129. Mohamed AA. Circulating adipokines in children with nonalcoholic fatty liver disease: possible noninvasive diagnostic markers. Ann Gastroenterol 2017; 30: 457-463.
130. Zwolak A, Szuster-Ciesielska A, Daniluk J, Semeniuk J, Kandefer-Szerszen M. Chemerin, retinol binding protein-4, cytokeratin-18 and transgelin-2 presence in sera of patients with non-alcoholic liver fatty disease. Ann Hepatol 2016; 15: 862-869.
131. Polyzos SA, Kountouras J, Mantzoros CS. Adipokines in nonalcoholic fatty liver disease. Metab Clin Exp 2016; 65: 1062-1079.
132. Yang S, Wang Q, Huang W, Song Y, Feng G, Zhou L, Tan J.Are serum chemerin levels different between obese and non-obese polycystic ovary syndrome women? Gynecol Endocr 2016; 32: 38-41.
133. Movahed Z, Kohan L, Fallahi S, Tabiee O. Influence of chemerin rs17173608 polymorphism on polycystic ovary syndrome susceptibility. Taiwan J Obstet Gynecol 2015; 54: 280-283.
134. Adrych K, Stojek M, Smoczynski M, Sledzinski T, Sylwia S, Swierczynski J. Increased serum chemerin concentration in patients with chronic pancreatitis. Dig Liver Dis 2012; 44: 393-397.
135. Shin H, Lee DC, Chu SH, Jeon JY, Lee MK, Im JA, Lee JW. Chemerin levels are positively correlated with abdominal visceral fat accumulation. Clin Endocrinol 2012; 77: 47-50.
136. Bremer AA, Jialal I. Adipose tissue dysfunction in nascent metabolic syndrome. J Obes 2013; 2013: 393192.
137. 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 Endocr Metabol 2013; 98: E514-E517.
138. Chu SH, Lee MK, Ahn KY, Im J, Park MS, Lee DC, Jeon JY, Lee JW. Chemerin and adiponectin contribute reciprocally to metabolic syndrome. PLoS One 2012; 7: e34710.
139. Aksan G, İnci S, Nar G, Soylu K, Gedikli Ö, Yüksel S, Özdemir M, Nar R, Meriç M, Şahin M. Association of serum chemerin levels with the severity of coronary artery disease in patients with metabolic syndrome. Int J Clin Exp Med 2014; 7: 5461-5468.
140. Eriksson JG, Venojärvi M, Osmond C. Prenatal and childhood growth, chemerin concentrations, and metabolic health in adult life. Int J Endocrinol 2016; 2016: 3838646.
141. Tönjes A, Scholz M, Breitfeld J, Marzi C, Grallert H, Gross A, Ladenvall C, Schleinitz D, Krause K, Kirsten H, Laurila E, Kriebel J, Thorand B, Rathmann W, Groop L, Prokopenko I, Isomaa B, Beutner F, Kratzsch J, Thiery J, Fasshauer M, Klöting N, Gieger C, Blüher M, Stumvoll M, Kovacs P. Genome wide meta-analysis highlights the role of genetic variation in RARRES2 in the regulation of circulating srum chemerin. PLoS Genet 2014; 10: e1004854.
142. Min JL, Nicholson G, Halgrimsdottir I, Almstrup K, Petri A, Barrett A, Travers M, Rayner NW, Mägi R, Pettersson FH, Broxholme J, Neville MJ, Wills QF, Cheeseman J; GIANT Consortium; MolPAGE Consortium, Allen M, Holmes CC, Spector TD, Fleckner J, McCarthy MI, Karpe F, Lindgren CM, Zondervan KT. Coexpression network analysis in abdominal and gluteal adipose tissue reveals regulatory genetic loci for metabolic syndrome and related phenotypes. PLoS Genet 2012; 8: e1002505.
143. Kataoka Y, Shibata R, Ohashi K, Kambara T, Enomoto T, Uemura Y, Ogura Y, Yuasa D, Matsuo K, Nagata T, Oba T, Yasukawa H, Numaguchi Y, Sone T, Murohara T, Ouchi N. Omentin prevents myocardial ischemic injury through AMP-activated protein kinase- and Akt-dependent mechanisms. J Am Coll Cardiol 2014; 63: 2722-2733.
144. Maruyama S, Shibata R, Kikuchi R, Izumiya Y, Rokutanda T, Araki S, Kataoka Y, Ohashi K, Daida H, Kihara S, Ogawa H, Murohara T, Ouchi N. Fat-derived factor omentin stimulates edothelial cell function and ischemia-induced revascularization via endothelial nitric oxide synthase-dependent mechanism. J Biol Chem 2012; 287: 408-417.
145. Brunetti L, Leone S, Orlando G, Ferrante C, Recinella L, Chiavaroli A, Di Nisio C, Shohreh R, Manippa F, Ricciu-ti A, Vacca M. Hypotensive effects of omentin-1 related to increased adiponectin and decreased interleukin-6 in intra-thoracic pericardial adipose tissue. Pharmacol Rep 2014; 66: 991-995.
146. Watanabe K, Watanabe R, Konii H, Shirai R, Sato K, Matsuyama T, Ishibashi-UedaH, Koba S, Kobayashi Y, Hirano T, Watanabe T. Counteractive effects of omentin-1 against atherogenesis. Cardiovasc Res 2016; 110: 118-128.
147. Duan XY, Xie PL, Ma YL, Tang SY. Omentin inhibits osteoblastic differentiation of calcifying vascular smooth muscle cells through the PI3K/Akt pathway. Amino Acids 2011; 41: 1223-1231.
148. Kazama K, Usui T, Okada M, Hara Y, Yamawaki H. Omentin plays an anti-inflammatory role through inhibition of TNF--induced superoxide production in vascular smooth muscle cells. Eur J Pharmacol 2012; 686: 116-123.
149. de Souza Batista CM, Yang RZ, Lee MJ, Glynn NM, Yu DZ, Pray J, Ndubuizu K, Patil S, Schwartz A, Kligman M, Fried SK, Gong DW, Shuldiner AR, Pollin TI, McLenithan JC. Omentin plasma levels and gene expression are decreased in obesity. Diabetes 2007; 56: 1655-1661.
150. Yan P, Liu D, Long M, Ren Y, Pang J, Li R. Changes of serum omentin levels and relationship between omentin and adiponectin concentrations in type 2 diabetes mellitus. Exp Clin Endocrinol Diabetes 2011; 119: 257-263.
151. Moreno-Navarrete J, Catalán V, Ortega F, Gómez-Ambrosi J, Ricart W, Frühbeck G, Fernández-Real JM. Circulating omentin concentration increases after weight loss. Nutr Metab 2010; 7: 27.
152. Lesná J, Tichá A, Hyšpler R, Musil F, Bláha V, Sobotka L, Zadák Z, Šmahelová A. Omentin-1 plasma levels and cholesterol metabolism in obese patients with diabetes mellitus type 1: impact of weight reduction. Nutr Diabetes 2015; 5: e183-e183.
153. Vu A, Sidhom MS, Bredbeck BC, Kosmiski LA, Aquilan-te CL. Evaluation of the relationship between circulating omentin-1 concentrations and components of the metabolic syndrome in adults without type 2 diabetes or cardiovascular disease. Diabetol Metab Syndr 2014; 6: 4.
154. Tan BK, Adya R, Farhatullah S, Lewandowski KC, O’Ha-re P, Lehnert H, Randeva HS. Omentin-1, a novel adipokine, is decreased in overweight insulin-resistant women with polycystic ovary syndrome: ex vivo and in vivo regulation of omentin-1 by insulin and glucose. Diabetes 2008; 57: 801-808.
155. Luque-Ramirez M, Martinez-Garcia MA, Montes-Nieto R, Fernandez-Duran E, Insenser M, Alpanes M, Escobar-Morreale HF. Sexual dimorphism in adipose tissue function as evidenced by circulating adipokine concentrations in the fasting state and after an oral glucose challenge. Hum Reprod 2013; 28: 1908-1918.
156. Zhou JY, Chan L, Zhou S. Omentin: linking metabolic syndrome and cardiovascular disease. Curr Vasc Pharmacol 2014; 12: 136-143.
157. Sitticharoon C, Nway NC, Chatree S, Churintaraphan M, Boonpuan P, Maikaew P. Interactions between adiponectin, visfatin, and omentin in subcutaneous and visceral adipose tissues and serum, and correlations with clinical and peripheral metabolic factors. Peptides 2014; 62: 164-175.
158. Wang C. Obesity, inflammation, and lung injury (OILI): the good. Mediators Inflamm 2014; 2014: 978463.
159. Zabetian-Targhi F, Mirzaei K, Keshavarz SA, Hossein-Nezhad A. Modulatory role of omentin-1 in inflammation: cytokines and dietary intake. J Am Coll Nutr 2016; 35: 670-678.
160. Barker G, Lim R, Georgiou HM, Lappas M. Omentin-1 is decreased in maternal plasma, placenta and adipose tissue of women with pre-existing obesity. PLoS One 2012; 7: e42943.
161. Montazerifar F, Bakhshipour A, Karajibani M, Torki Z, Dashipour A. Serum omentin-1, vaspin, and apelin levels and central obesity in patients with nonalcoholic fatty liver disease. J Res Med Sci 2017; 22: 70.
162. Catli G, Anik A, Abaci A, Kume T, Bober E. Low omentin-1 levels are related with clinical and metabolic parameters in obese children. Exp Clin Endocr Diabetes 2013; 121: 595-600.
163. Oświęcimska J, Suwała A, Świętochowska E, Ostrowska Z, Gorczyca P, Ziora-Jakutowicz K, Machura E, Szczepańska M, Kukla M, Stojewska M, Ziora D, Ziora K. Serum omentin levels in adolescent girls with anorexia nervosa and obesity. Physiol Res 2015; 64: 701-709.
164. Zhang M, Tan X, Yin C, Wang L, Tie Y, Xiao Y. Serum levels of omentin-1 are increased after weight loss and are particularly associated with increases in obese children with metabolic syndrome. Acta Paediatr 2017; 106: 1851-1856.
165. Hamnvik OP, Thakkar B, Chamberland J, Aronis K, Schneider B, Mantzoros CS. Omentin-1 levels are reduced by pharmacologic doses of leptin, but remain unaffected by energy deprivation and display no day–night variation. Int J Obes 2015; 39: 260-264.
166. Nway NC, Sitticharoon C, Chatree S, Maikaew P. Correlations between the expression of the insulin sensitizing hormones, adiponectin, visfatin, and omentin, and the appetite regulatory hormone, neuropeptide Y and its receptors in subcutaneous and visceral adipose tissues. Obes Res Clin Pract 2016; 10: 256-263.
167. Splichal Z, Bienertova-Vasku J, Novak J, Zlamal F, Tomandl J, Tomandlova M, Forejt M, Havlenova S, Jackowska A, Vasku A. The common polymorphism Val109Asp in the omentin gene is associated with daily energy intake in the Central-European population. Nutr Neurosci 2015; 18: 41-48.
168. Isakova ZT, Talaibekova ET, Asambaeva DA, Kerimkulova AS, Lunegova OS, Aldasheva NM, Aldashev AA. A polymorphic marker Val109Asp in the omentin gene are associated with abdominal obesity in the Kyrgyz population. Probl Endocrinol 2016; 62: 4-8.
169. Saremi A, Asghari M, Ghorbani A. Effects of aerobic training on serum omentin-1 and cardiometabolic risk factors in overweight and obese men. J Sports Sci 2010; 28: 993-998.
170. Ouerghi N, Ben Fradj MK, Bezrati I, Feki M, Kaabachi N, Bouassida A. Effect of high-intensity interval training on plasma omentin-1 concentration in overweight/obese and normal-weight youth. Obes Facts 2017; 10: 323-331.
171. Wilms B, Ernst B, Gerig R, Schultes B. Plasma omentin-1 levels are related to exercise performance in obese women and increase upon aerobic endurance training. Exp Clin Endocrinol Diab 2015; 123: 187-192.
172. Zehsaz F, Farhangi N, Ghahramani M. The response of circulating omentin-1 concentration to 16-week exercise training in male children with obesity. Phys Sportsmed 2016; 44: 355-361.
173. Pan HY, Guo L, Li Q. Changes of serum omentin-1 levels in normal subjects and in patients with impaired glucose regulation and with newly diagnosed and untreated type 2 diabetes. Diab Res Clin Pract 2010; 88: 29-33.
174. Schäffler A, Neumeier M, Herfarth H, Fürst A, Schölmerich J, Büchler C. Genomic structure of human omentin, a new adipocytokine expressed in omental adipose tissue. Biochim Biophys Acta 2005; 1732: 96-102.
175. Akour A, Kasabri V, Boulatova N, Bustanji Y, Naffa R, Hyasat D, Khawaja N, Bustanji H, Zayed A, Momani M. Levels of metabolic markers in drug-naive prediabetic and type 2 diabetic patients. Acta Diabetol 2017; 54: 163-170.
176. Arman Y, Kirna K, Ugurlukisi B, Kutlu O, Dikker O, Cil E, Akarsu M, Ozcan M, Yuruyen G, Demir P, Altun O, Ozsenel EB, Erdem MG, Sandikci R, Tukek T. The effects of blood glucose regulation in omentin-1 levels among diabetic patients. Exp Clin Endocrinol Diabetes 2017; 125: 262-266.
177. Wan W, Li Q, Zhang F, Zheng G, Lv Y, Wan G, Jin X. Serum and vitreous concentrations of omentin-1 in diabetic retinopathy. Dis Markers 2015; 2015: 754312.
178. Tang Y, Yu J, Zeng Z, Liu Y, Liu J, Xu J. Circulating omentin-1 levels in women with polycystic ovary syndrome: a meta-analysis. Gynecol Endocrinol 2017; 33: 244-249.
179. Zirlik S, Hildner KM, Targosz A, Neurath MF, Fuchs FS, Brzozowski T, Konturek PC. Melatonin and omentin: influence factors in the obstructive sleep apnoea syndrome? J Physiol Pharmacol 2013; 64: 353-360.
180. Wang Q, Feng X, Zhou C, Li P, Kang J. Decreased levels of serum omentin-1 in patients with obstructive sleep apnoea syndrome. Ann Clin Biochem 2013; 50: 230-235.
181. Senolt L, Polanska M, Filkova M, Cerezo LA, Pavelka K, Gay S, Haluzik M, Vencovsky J. Vaspin and omentin: new adipokines differentially regulated at the site of inflammation in rheumatoid arthritis. Ann Rheum Dis 2010; 69: 1410-1411.
182. Wittenbecher C, Menzel J, Carstensen-Kirberg M, Biemann R, di Giuseppe R, Fritsche A, et al. Omentin-1, adiponectin, and the risk of developing type 2 diabetes. Diabetes Care 2016; 39: e79-e80.
183. Herder C, Kannenberg JM, Niersmann C, Huth C, Carstensen-Kirberg M, Wittenbecher C, Schulze MB, Blüher M, Rathmann W, Peters A, Roden M, Meisinger C, Thorand B. Independent and opposite associations of serum levels of omentin-1 and adiponectin with increases of glycaemia and incident type 2 diabetes in an older population: KORA F4/FF4 study. Eur J Endocrinol 2017; 177: 277-286.
184. Yilmaz Y, Yonal O, Kurt R, Alahdab YO, Eren F, Ozdogan O, Celikel CA, Imeryuz N, Kalayci C, Avsar E. Serum levels of omentin, chemerin and adipsin in patients with biopsy-proven nonalcoholic fatty liver disease. Scand J Gastroenterol 2011; 46: 91-97.
185. Harada K, Shibata R, Ouchi N, Tokuda Y, Funakubo H, Suzuki M, Kataoka T, Nagao T, Okumura S, Shinoda N, Kato B, Sakai S4, Kato M, Marui N, Ishii H, Amano T, Matsubara T, Murohara T.. Increased expression of the adipocytokine omentin in the epicardial adipose tissue of coronary artery disease patients. Atherosclerosis 2016; 251: 299-304.
186. Yoruk U, Yaykasli KO, Ozhan H, Memisogullari R, Karabacak A, Bulur S, Aslantaş Y, Başar C, Kaya E. Association of omentin Val109Asp polymorphism with coronary artery disease. Anatol J Cardiol 2014; 14: 511-514.
187. Jamshidi J, Ghanbari M, Asnaashari A, Jafari N, Valizadeh GA. Omentin Val109Asp polymorphism and risk of coronary artery disease. Asian Cardiovasc Thorac Ann 2017; 25: 199-203.
188. Nazar S, Zehra S, Azhar A. Association of single nucleotide missence polymorphism Val109Aspof omentin-1 gene and coronary artery disease in Pakistani population: multicenter study. Pakistan J Med Sci 2017; 33: 1128-1135.
189. Shibata R, Ouchi N, Takahashi R, Terakura Y, Ohashi K, Ikeda N, Higuchi A, Terasaki H, Kihara S, Murohara T. Omentin as a novel biomarker of metabolic risk factors. Diabetol Metab Syndr 2012; 4: 37.
190. Liu R, Wang X, Bu P. Omentin-1 is associated with carotid atherosclerosis in patients with metabolic syndrome. Diab Res Clin Pract 2011; 93: 21-25.
191. Alizadeh S, Mirzaei K, Mohammadi C, Keshavarz SA, Maghbooli Z. Circulating omentin-1 might be associated with metabolic health status in different phenotypes of body size. Arch Endocrinol Metab 2017; 61: 567-574.
192. Kilic DC, Oguz A, Uzunlulu M, Celik S, Koroglu G. Plasma omentin-1 levels are similar in nondiabetic metabolic syndrome patients and healthy subjects. J Endocrinol Metab 2011; 1: 182-187.
193. Prats-Puig A, Bassols J, Bargalló E, Mas-Parareda M, Ribot R, Soriano-Rodríguez P, Berengüí À, Díaz M, de Zegher F, Ibánez L, López-Bermejo A. Toward an early marker of metabolic dysfunction: Omentin-1 in prepubertal children. Obesity 2011; 19: 1905-1907.
194. Buyukinan M, Atar M, Can U, Pirgon O, Guzelant A, Deniz I. The association between serum vaspin and omentin-1 levels in obese children with metabolic syndrome. Metab Syndr Rel Disord 2018; 16: 76-81.

Address for correspondence:

Monika Wawszczak Genetic Laboratory
Institute of Medical Sciences
Faculty of Medicine and Health Sciences
Jan Kochanowski University
Al. IX Wieków Kielc 19a
25-516 Kielce, Poland
Phone: +48 503 772 301
E-mail: wawszczak.monika@gmail.com