http://informahealthcare.com/gye ISSN: 0951-3590 (print), 1473-0766 (electronic) Gynecol Endocrinol, Early Online: 1–4 ! 2014 Informa UK Ltd. DOI: 10.3109/09513590.2014.968547
ORIGINAL PAPER
Chemerin as a marker of body fat and insulin resistance in women with polycystic ovary syndrome Daniel H. Kort, Alessandra Kostolias, Chantae Sullivan, Roger A. Lobo
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Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons, New York, NY, USA Abstract
Keywords
Adipocytokines may alter normal metabolic function and play an important role in the pathophysiology of polycystic ovary syndrome (PCOS). We prospectively evaluated a cohort of obese and non-obese women with PCOS and non-PCOS controls for both novel (chemerin and omentin-1) and established (leptin and adiponectin) adipokines. Compared with age-matched controls, non-obese women with PCOS had decreased serum omentin-1 (191.1 ng/ml versus 269.7 ng/ml, p ¼ 0.0001), while serum chemerin was not significantly altered in women with PCOS (53.95 ng/ml versus 48.61 ng/ml, p ¼ 0.11). The findings were similar in the entire group of women with PCOS. However, in women with PCOS, chemerin correlated with leptin (r ¼ 0.508, p ¼ 0.004), adiponectin (r ¼ 0.36, p ¼ 0.014), and the leptin/adiponectin (L/A) ratio (r ¼ 0.605, p50.0001), while there were no such correlations with omentin-1. In women with PCOS, chemerin correlated with BMI (r ¼ 0.317, p ¼ 0.034), abdominal subcutaneous fat (r ¼ 0.451, p ¼ 0.0019), and insulin resistance (HOMA-IR, r ¼ 0.428, p ¼ 0.0034), while omentin-1 did not correlate with any parameter. These data suggest that chemerin although not significantly elevated in women with PCOS correlates with adiposity and insulin resistance, and it is the single best adipokine measured in this regard. Chemerin, through its inflammatory role as a chemo-attractant in adipose tissue, may be an important determinant of insulin resistance in PCOS.
Body Mass Index, insulin resistance, polycystic ovary syndrome
Introduction Polycystic ovary syndrome (PCOS) is the most common endocrinopathy of reproductive-aged women and is associated with obesity, insulin resistance, and possibly an increased risk of cardiovascular disease [1]. Even among non-obese women with PCOS, the central or abdominal fat content is increased [2]. Abdominal adipose tissue secretes adipocytokines, also known as adipokines, which have been shown to be directly related to increased insulin resistance and a worse metabolic profile in women with PCOS [3,4]. Serum adipocytokine levels correlate with the overall fat content in women with PCOS and are altered in women with PCOS compared with age- and weight-matched controls [5,6]. However, some of these data are conflicting [5]. Two more recently discovered adipokines, omentin-1 and chemerin, have received a fair amount of attention in studies of insulin resistance and metabolic syndrome; however, there are few reports of the significance of levels of omentin-1 and chemerin in women with PCOS [7–14]. We and others have reported results of studies in women with PCOS regarding measurements of leptin and adiponectin, which are more established adipokines [2–4]. In this regard, adiponectin levels, which are lower in women with PCOS,
Address for correspondence: Daniel H. Kort, Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons, 622 W, 168th Street, PH-16, New York, NY 10032, USA. Tel: +1 212 305 6337. Fax: +1 212 305 4326. E-mail: [email protected]
History Received 10 June 2014 Accepted 19 September 2014 Published online 8 October 2014
appear to be an independent marker of insulin resistance, even when controlling for Body Mass Index (BMI) [2,6]. Here we wished to determine the clinical value of measurements of omentin-1 and chemerin in women with PCOS through a wide range of body masses, in terms of their correlation with fat content and insulin resistance. We also wished to compare the value of these measurements and correlations with those which are known to exist between leptin and adiponectin and body mass and insulin resistance. In this prospectively designed study, we also divided women with PCOS into those who were obese and non-obese; the latter group being matched to a control population of normal women.
Materials and methods All procedures were approved by the Columbia University Institutional Review Board. We recruited 45 women aged 18–38 with PCOS by Rotterdam criteria (oligomenorrhea or amenorrhea and either (a) clinical or biochemical evidence of hyperandrogenism or (b) ultrasound findings of polycystic ovaries). In addition, 23 age-matched controls were recruited for the study. Twenty-two women with PCOS were matched by age and BMI to the 23 controls to assess the values of the adipokines without the variable body mass. All subjects, PCOS and controls, were assessed in the early follicular phase of a normal menstrual cycle or after progestin-induced menses in the case of PCOS. BMI (kg/m2), abdominal subcutaneous fat thickness (cm, measured via ultrasound [6]), and insulin resistance (homeostasis model of insulin resistance (HOMA-IR) ¼ glucose
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(mmol/l) insulin (mU/l)/22.5) were measured. Serum levels of chemerin, omentin-1, leptin, and adiponectin were measured in both groups by enzyme-linked immunoabsorbent assay (Millipore, Billerica, MA). The intra-assay and inter-assay coefficients of variation were 8.6% and 4.2% (chemerin), 3.9% and 7.9% (omentin-1), 8.3% and 5.8% (leptin), and 5.8% and 6.2% (adiponectin), respectively. Serum levels of total testosterone (T), dehydroepiandrosterone sulfate (DHEA-S), and sex-hormone-binding globulin (SHBG) were measured in the PCOS group by enzyme-linked immunoabsorbent assay (Millipore, Billerica, MA). Serum adipocytokine levels were compared between the PCOS groups and age-matched controls using unpaired t-tests with a type I error of 0.05 used to determine the significance. Correlations between chemerin and omentin-1 and the more established adipocytokines, leptin and adiponectin, in women with PCOS were calculated using Spearman correlation coefficients. Correlation between measured adipocytokines and metabolic parameters (BMI, subcutaneous fat thickness, and HOMA-IR) was calculated using Spearman correlation coefficients.
Results Forty-five women aged 38 ± 4.3 with PCOS and 23 women without PCOS (controls) aged 27 ± 5.4 were included in the study. Women with PCOS had a higher BMI (33.2 ± 0.86 versus 23.4 ± 0.86). Women with PCOS had an irregular menstrual function (avg. # cycles month 0.45 ± 0.2), while controls had uniformly regular menses. Hyperandrogenism was confirmed in the PCOS group where testosterone levels (55.7 ± 8.6 ng/dl) and DHEA-S levels (1.78 ± 0.19 mg/ml) were elevated above the established normal range. Compared with controls, for the entire group of women with PCOS, serum omentin-1 levels were significantly lower (191.1 ng/ ml versus 269.7 ng/ml, p ¼ 0.0001). Chemerin levels were slightly higher in the PCOS group, but did not achieve statistical significance (53.95 ng/ml versus 48.61 ng/ml, p ¼ 0.11). In the PCOS group, the leptin level was increased (26.11 ng/ml versus 10.04 ng/ml, p50.0001), the adiponectin level was decreased (8.17 ng/ml versus 13.71 ng/ml, p ¼ 0.0004.), and the L/A ratio was increased (4.38 versus 1.02, p50.0001) compared with controls (Figure 1). Figure 1. Comparison of serum adipocytokine level between women with PCOS and age-matched controls. Statistically significant difference (p50.05).
Gynecol Endocrinol, Early Online: 1–4
In order to control the potential effect of obesity on adipokine production, the subgroup of non-obese women with PCOS (BMI530, n ¼ 22) was compared with controls. When compared with controls, non-obese women with PCOS also had lower serum omentin-1 levels (197.6 ng/ml versus 269.7 ng/ml, p ¼ 0.0073). Chemerin values were similar to those of the entire group of PCOS although higher values were not statistically different (50.04 ng/ml versus 48.61 ng/ml, p ¼ 0.72). In this non-obese subgroup, leptin levels remained elevated (20.49 ng/ml versus 10.04 ng/ml, p50.0001), and adiponectin levels were lower (9.42 versus 13.71, p ¼ 0.0433). To investigate the relationship of the novel adipokines, chemerin and omentin-1, with the more established adipocytokines, leptin and adiponectin, Spearman correlation coefficients were calculated between the different adipocytokines in women with PCOS. Omentin-1 was not significantly correlated with leptin, adiponectin, or the L/A ratio (Table 1). However, chemerin was positively correlated with leptin (r ¼ 0.508, p ¼ 0.004), negatively correlated with adiponectin (r ¼ 0.363, p ¼ 0.014), and positively correlated with the L/A ratio (r ¼ 0.605, p50.0001). In order to investigate the relationship between serum adipocytokine levels and abnormal metabolic function, Spearman correlation coefficients were calculated among adipocytokines and BMI, subcutaneous fat thickness, and insulin resistance (HOMA-IR) (Table 2). Serum omentin-1 did not correlate with any marker, whereas chemerin levels correlated positively with all three measurements (Figure 2) and serum leptin levels correlated positively with BMI and subcutaneous fat thickness. Adiponectin correlated weakly with insulin resistance. There was no significant correlation among testosterone, DHEA-S and SHBG, and any of the adipokines. Table 1. Correlation of chemerin and omentin-1 with established adipocytokines in PCOS.
Leptin Adiponectin L/A ratio
Chemerin (r)
Omentin-1 (r)
0.508 (p ¼ 0.004) 0.363 (p ¼ 0.014) 0.605 (p50.0001)
0.055 (NS) 0.189 (NS) 0.091 (NS)
Chemerin in PCOS
DOI: 10.3109/09513590.2014.968547
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Table 2. Correlations of chemerin, omentin-1, adiponectin, leptin, and the L/A ratio with markers of adiposity and insulin resistance in PCOS.
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BMI SQ fat HOMA-IR
Chemerin (r)
Omentin-1 (r)
Adiponectin (r)
Leptin (r)
L/A ratio (r)
0.317 (p ¼ 0.034) 0.451 (p ¼ 0.0019) 0.428 (p ¼ 0.0034)
0.014 (NS) 0.015 (NS) 0.049 (NS)
0.2 (NS) 0.19 (NS) 0.3301 (p ¼ 0.027)
0.508 (p ¼ 0.004) 0.355 (p ¼ 0.017) 0.254 (p ¼ 0.092)
0.468 (p ¼ 0.0012) 0.371 (p ¼ 0.012) 0.376 (p ¼ 0.011)
Figure 2. Correlation of chemerin with SQ fat (a) and HOMA-IR (b).
Discussion Despite the strong association between altered adiposity and PCOS, the precise link between the two and how adiposity is linked to insulin resistance are incompletely understood. Hormones secreted by adipocytes, termed adipocytokines or adipokines, are altered in women with PCOS and may be a signal that mediates abnormal metabolic and reproductive function. The purpose of this study was to better characterize two novel adipokines, chemerin and omentin. While these adipokines have been studied in adults with metabolic syndrome, diabetes, and insulin resistance before and after various interventions [8,11–14], there are few data about these adipokines in PCOS. Preliminary data in the literature have suggested that levels of omentin-1 are decreased and levels of chemerin are increased in women with PCOS [7,9]. There are no data to our knowledge, however, on how these novel adipokines are compared with other more established adipokines, leptin and adiponectin, in correlating with adiposity and insulin resistance in PCOS. Our major purpose was not to check whether omentin-1 and chemerin levels are decreased or elevated in women with PCOS. We selected a large group of well-characterized women with a large range of body masses to be able to find correlations with adiposity and insulin resistance, and to compare these findings with those of leptin and adiponectin. Nevertheless, we carried out an analysis of the differences in adipokine levels in a subgroup of non-obese women with PCOS and controls. In this analysis, we
found that omentin-1 levels were lower in PCOS, but chemerin was not significantly higher in the entire PCOS group or the nonobese PCOS group. This finding is interesting in that chemerin appeared to correlate better than any other single adipokine with fat mass and insulin resistance. In the non-obese PCOS group, while we confirmed that adiponectin was lower in women with PCOS, leptin was higher. This is different from our previous data with weight-matched groups [3], but is not inconsistent with other reports [5]. The heterogeneity in adiposity and hyperandrogenism of different population of women with PCOS who have been studied may explain the inconsistent results regarding the levels of leptin in PCOS [15]. In a recent study, serum chemerin levels were increased in women with PCOS compared with weight-matched controls [7]. The increase in chemerin persisted when the obese (BMI425) PCOS group was compared with the obese control group, suggesting that obesity is not the only determining factor. In a different study, both serum chemerin and omental adipose chemerin were significantly higher in women with PCOS compared with age- and weight-matched controls [16]. Ex vivo treatment showed that chemerin synthesis and production was increased by insulin and decreased by metformin, suggesting that chemerin may be a link between hyperinsulinemia and PCOS. Chemerin absolute levels were also numerically different in the recent study [7] and what we report here, although our levels are more compatible with many other reports in non-PCOS populations [8,11]. Thus, heterogeneity in assay conditions between studies may be confounding the findings. Nevertheless, our report stresses the correlations with adiposity and insulin resistance. Here, chemerin correlated significantly with BMI, subcutaneous fat mass, and HOMA-IR. In this regard, chemerin was the single best correlate of these parameters, and rivaled that of the L/A ratio. Of interest, although omentin-1 levels were lower in PCOS, serum omentin did not correlate with any parameter, including a lack of correlation with the other adipokines. This may relate to the fact that omentin-1 is the product of the stromal vasculature in adipose tissue, rather than from adipocytes per se. Chemerin was the only adipokine tested to be positively associated with all three measures of adiposity and insulin resistance in PCOS. This finding is consistent with prior studies in both the PCOS and non-PCOS populations, which show chemerin to be positively associated with glucose response, insulin resistance, metabolic syndrome, and coronary artery disease [7,8,11]. As chemerin is a chemo-attractant adipokine with inflammatory properties, chemerin may be one of the most important links between adiposity and insulin resistance, and thus a good clinical marker for metabolic dysfunction. However, serum levels may not always reflect these changes as levels are determined by both the type and the abundance of adipose tissue, which by nature can be heterogeneous. In contrast, our findings on omentin-1 were completely negative. Serum omentin-1 levels had no association with markers of abnormal adiposity or insulin resistance in the groups tested, perhaps due to its origin of production as discussed above. Omentin-1 levels have been reported to be negatively associated with PCOS in some studies, but not others [5,7,10,11]. Therefore,
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omentin-1 is unlikely to be a good marker for PCOS or its associated metabolic dysfunction. In conclusion, we report that chemerin is a novel adipocytokine that appears to be an important physiological modulator of metabolic dysfunction in PCOS and is the single best correlate of adiposity and insulin resistance in women with PCOS, even though levels are not consistently elevated. More studies in the future will be needed to determine whether chemerin has clinical utility and to uncover differences in different phenotypes of PCOS which may help explain heterogeneity in the data.
Acknowledgements The authors would like to thank Jolene Lalas and Luz Sanabria from the Department of OBGYN, Columbia University for their assistance in patient recruitment and data collection. All parties consent to acknowledgement.
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Declaration of interest The authors report no declarations of interest. The authors would like to thank The Endocrine Fellows Foundation for providing the financial support for endocrine assays.
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References 1. Goodarzi MO, Dumesic DA, Chazenbalk G, Azziz R. Polycystic ovary syndrome: etiology, pathogenesis and diagnosis. Nat Rev Endocrinol 2011;7:219–31. 2. Carmina E, Bucchieri S, Mansueto P, et al. Circulating levels of adipose products and differences in fat distribution in the ovulatory and anovulatory phenotypes of polycystic ovary syndrome. Fertil Steril 2009;91:1332–5. 3. Carmina E, Orio F, Palomba S, et al. Evidence for altered adipocyte function in polycystic ovary syndrome. Eur J Endocrinol/Eur Fed Endocr Soc 2005;152:389–94. 4. Vardhana PA, Dicken C, Tortoriello DV, et al. Increasing adiposity in normal ovulatory women affects adipocytokine expression in
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subcutaneous and visceral abdominal fat. Int J Gynaecol Obstet: Off Organ Int Fed Gynaecol Obstet 2009;104:121–4. Chen X, Jia X, Qiao J, et al. Adipokines in reproductive function: a link between obesity and polycystic ovary syndrome. J Mol Endocrinol 2013;50:R21–37. Carmina E, Chu C, Moran C, et al. Subcutaneous and omental fat expression of adiponectin and leptin in women with polycystic ovary syndrome. Fertil Steril 2008;89:642–8. Guzel EC, Celik C, Abali R, et al. Omentin and chemerin and their association with obesity in women with polycystic ovary syndrome. Gynecol Endocrinol: Off J Int Soc Gynecol Endocrinol 2014;30:419–22. Chu SH, Lee MK, Ahn KY, et al. Chemerin and adiponectin contribute reciprocally to metabolic syndrome. PloS One 2012;7: e34710. Mahde A, Shaker M, Al-Mashhadani Z. Study of omentin 1 and other adipokines and hormones in PCOS patients. Oman Med J 2009;24:108–18. Choi JH, Rhee EJ, Kim KH, et al. Plasma omentin-1 levels are reduced in non-obese women with normal glucose tolerance and polycystic ovary syndrome. Eur J Endocrinol/Eur Fed Endocr Soc 2011;165:789–96. Jialal I, Devaraj S, Kaur H, et al. Increased chemerin and decreased omentin-1 in both adipose tissue and plasma in nascent metabolic syndrome. J Clin Endocrinol Metabol 2013;98:E514–17. Bozaoglu K, Bolton K, McMillan J, et al. Chemerin is a novel adipokine associated with obesity and metabolic syndrome. Endocrinology 2007;148:4687–94. Lee MK, Chu SH, Lee DC, et al. The association between chemerin and homeostasis assessment of insulin resistance at baseline and after weight reduction via lifestyle modifications in young obese adults. Clin Chim Acta 2013;421:109–15. Stefanov T, Bluher M, Vekova A, et al. Circulating chemerin decreases in response to a combined strength and endurance training. Endocrine 2014;45:382–91. Jacobs HS, Conway GS. Leptin, polycystic ovaries and polycystic ovary syndrome. Hum Reprod Update 1999;5:166–71. Tan BK, Chen J, Farhatullah S, et al. Insulin and metformin regulate circulating and adipose tissue chemerin. Diabetes 2009;58: 1971–7.
ORIGINAL PAPER
Chemerin as a marker of body fat and insulin resistance in women with polycystic ovary syndrome Daniel H. Kort, Alessandra Kostolias, Chantae Sullivan, Roger A. Lobo
Gynecol Endocrinol Downloaded from informahealthcare.com by Universitaet Zuerich on 12/31/14 For personal use only.
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons, New York, NY, USA Abstract
Keywords
Adipocytokines may alter normal metabolic function and play an important role in the pathophysiology of polycystic ovary syndrome (PCOS). We prospectively evaluated a cohort of obese and non-obese women with PCOS and non-PCOS controls for both novel (chemerin and omentin-1) and established (leptin and adiponectin) adipokines. Compared with age-matched controls, non-obese women with PCOS had decreased serum omentin-1 (191.1 ng/ml versus 269.7 ng/ml, p ¼ 0.0001), while serum chemerin was not significantly altered in women with PCOS (53.95 ng/ml versus 48.61 ng/ml, p ¼ 0.11). The findings were similar in the entire group of women with PCOS. However, in women with PCOS, chemerin correlated with leptin (r ¼ 0.508, p ¼ 0.004), adiponectin (r ¼ 0.36, p ¼ 0.014), and the leptin/adiponectin (L/A) ratio (r ¼ 0.605, p50.0001), while there were no such correlations with omentin-1. In women with PCOS, chemerin correlated with BMI (r ¼ 0.317, p ¼ 0.034), abdominal subcutaneous fat (r ¼ 0.451, p ¼ 0.0019), and insulin resistance (HOMA-IR, r ¼ 0.428, p ¼ 0.0034), while omentin-1 did not correlate with any parameter. These data suggest that chemerin although not significantly elevated in women with PCOS correlates with adiposity and insulin resistance, and it is the single best adipokine measured in this regard. Chemerin, through its inflammatory role as a chemo-attractant in adipose tissue, may be an important determinant of insulin resistance in PCOS.
Body Mass Index, insulin resistance, polycystic ovary syndrome
Introduction Polycystic ovary syndrome (PCOS) is the most common endocrinopathy of reproductive-aged women and is associated with obesity, insulin resistance, and possibly an increased risk of cardiovascular disease [1]. Even among non-obese women with PCOS, the central or abdominal fat content is increased [2]. Abdominal adipose tissue secretes adipocytokines, also known as adipokines, which have been shown to be directly related to increased insulin resistance and a worse metabolic profile in women with PCOS [3,4]. Serum adipocytokine levels correlate with the overall fat content in women with PCOS and are altered in women with PCOS compared with age- and weight-matched controls [5,6]. However, some of these data are conflicting [5]. Two more recently discovered adipokines, omentin-1 and chemerin, have received a fair amount of attention in studies of insulin resistance and metabolic syndrome; however, there are few reports of the significance of levels of omentin-1 and chemerin in women with PCOS [7–14]. We and others have reported results of studies in women with PCOS regarding measurements of leptin and adiponectin, which are more established adipokines [2–4]. In this regard, adiponectin levels, which are lower in women with PCOS,
Address for correspondence: Daniel H. Kort, Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons, 622 W, 168th Street, PH-16, New York, NY 10032, USA. Tel: +1 212 305 6337. Fax: +1 212 305 4326. E-mail: [email protected]
History Received 10 June 2014 Accepted 19 September 2014 Published online 8 October 2014
appear to be an independent marker of insulin resistance, even when controlling for Body Mass Index (BMI) [2,6]. Here we wished to determine the clinical value of measurements of omentin-1 and chemerin in women with PCOS through a wide range of body masses, in terms of their correlation with fat content and insulin resistance. We also wished to compare the value of these measurements and correlations with those which are known to exist between leptin and adiponectin and body mass and insulin resistance. In this prospectively designed study, we also divided women with PCOS into those who were obese and non-obese; the latter group being matched to a control population of normal women.
Materials and methods All procedures were approved by the Columbia University Institutional Review Board. We recruited 45 women aged 18–38 with PCOS by Rotterdam criteria (oligomenorrhea or amenorrhea and either (a) clinical or biochemical evidence of hyperandrogenism or (b) ultrasound findings of polycystic ovaries). In addition, 23 age-matched controls were recruited for the study. Twenty-two women with PCOS were matched by age and BMI to the 23 controls to assess the values of the adipokines without the variable body mass. All subjects, PCOS and controls, were assessed in the early follicular phase of a normal menstrual cycle or after progestin-induced menses in the case of PCOS. BMI (kg/m2), abdominal subcutaneous fat thickness (cm, measured via ultrasound [6]), and insulin resistance (homeostasis model of insulin resistance (HOMA-IR) ¼ glucose
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(mmol/l) insulin (mU/l)/22.5) were measured. Serum levels of chemerin, omentin-1, leptin, and adiponectin were measured in both groups by enzyme-linked immunoabsorbent assay (Millipore, Billerica, MA). The intra-assay and inter-assay coefficients of variation were 8.6% and 4.2% (chemerin), 3.9% and 7.9% (omentin-1), 8.3% and 5.8% (leptin), and 5.8% and 6.2% (adiponectin), respectively. Serum levels of total testosterone (T), dehydroepiandrosterone sulfate (DHEA-S), and sex-hormone-binding globulin (SHBG) were measured in the PCOS group by enzyme-linked immunoabsorbent assay (Millipore, Billerica, MA). Serum adipocytokine levels were compared between the PCOS groups and age-matched controls using unpaired t-tests with a type I error of 0.05 used to determine the significance. Correlations between chemerin and omentin-1 and the more established adipocytokines, leptin and adiponectin, in women with PCOS were calculated using Spearman correlation coefficients. Correlation between measured adipocytokines and metabolic parameters (BMI, subcutaneous fat thickness, and HOMA-IR) was calculated using Spearman correlation coefficients.
Results Forty-five women aged 38 ± 4.3 with PCOS and 23 women without PCOS (controls) aged 27 ± 5.4 were included in the study. Women with PCOS had a higher BMI (33.2 ± 0.86 versus 23.4 ± 0.86). Women with PCOS had an irregular menstrual function (avg. # cycles month 0.45 ± 0.2), while controls had uniformly regular menses. Hyperandrogenism was confirmed in the PCOS group where testosterone levels (55.7 ± 8.6 ng/dl) and DHEA-S levels (1.78 ± 0.19 mg/ml) were elevated above the established normal range. Compared with controls, for the entire group of women with PCOS, serum omentin-1 levels were significantly lower (191.1 ng/ ml versus 269.7 ng/ml, p ¼ 0.0001). Chemerin levels were slightly higher in the PCOS group, but did not achieve statistical significance (53.95 ng/ml versus 48.61 ng/ml, p ¼ 0.11). In the PCOS group, the leptin level was increased (26.11 ng/ml versus 10.04 ng/ml, p50.0001), the adiponectin level was decreased (8.17 ng/ml versus 13.71 ng/ml, p ¼ 0.0004.), and the L/A ratio was increased (4.38 versus 1.02, p50.0001) compared with controls (Figure 1). Figure 1. Comparison of serum adipocytokine level between women with PCOS and age-matched controls. Statistically significant difference (p50.05).
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In order to control the potential effect of obesity on adipokine production, the subgroup of non-obese women with PCOS (BMI530, n ¼ 22) was compared with controls. When compared with controls, non-obese women with PCOS also had lower serum omentin-1 levels (197.6 ng/ml versus 269.7 ng/ml, p ¼ 0.0073). Chemerin values were similar to those of the entire group of PCOS although higher values were not statistically different (50.04 ng/ml versus 48.61 ng/ml, p ¼ 0.72). In this non-obese subgroup, leptin levels remained elevated (20.49 ng/ml versus 10.04 ng/ml, p50.0001), and adiponectin levels were lower (9.42 versus 13.71, p ¼ 0.0433). To investigate the relationship of the novel adipokines, chemerin and omentin-1, with the more established adipocytokines, leptin and adiponectin, Spearman correlation coefficients were calculated between the different adipocytokines in women with PCOS. Omentin-1 was not significantly correlated with leptin, adiponectin, or the L/A ratio (Table 1). However, chemerin was positively correlated with leptin (r ¼ 0.508, p ¼ 0.004), negatively correlated with adiponectin (r ¼ 0.363, p ¼ 0.014), and positively correlated with the L/A ratio (r ¼ 0.605, p50.0001). In order to investigate the relationship between serum adipocytokine levels and abnormal metabolic function, Spearman correlation coefficients were calculated among adipocytokines and BMI, subcutaneous fat thickness, and insulin resistance (HOMA-IR) (Table 2). Serum omentin-1 did not correlate with any marker, whereas chemerin levels correlated positively with all three measurements (Figure 2) and serum leptin levels correlated positively with BMI and subcutaneous fat thickness. Adiponectin correlated weakly with insulin resistance. There was no significant correlation among testosterone, DHEA-S and SHBG, and any of the adipokines. Table 1. Correlation of chemerin and omentin-1 with established adipocytokines in PCOS.
Leptin Adiponectin L/A ratio
Chemerin (r)
Omentin-1 (r)
0.508 (p ¼ 0.004) 0.363 (p ¼ 0.014) 0.605 (p50.0001)
0.055 (NS) 0.189 (NS) 0.091 (NS)
Chemerin in PCOS
DOI: 10.3109/09513590.2014.968547
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Table 2. Correlations of chemerin, omentin-1, adiponectin, leptin, and the L/A ratio with markers of adiposity and insulin resistance in PCOS.
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BMI SQ fat HOMA-IR
Chemerin (r)
Omentin-1 (r)
Adiponectin (r)
Leptin (r)
L/A ratio (r)
0.317 (p ¼ 0.034) 0.451 (p ¼ 0.0019) 0.428 (p ¼ 0.0034)
0.014 (NS) 0.015 (NS) 0.049 (NS)
0.2 (NS) 0.19 (NS) 0.3301 (p ¼ 0.027)
0.508 (p ¼ 0.004) 0.355 (p ¼ 0.017) 0.254 (p ¼ 0.092)
0.468 (p ¼ 0.0012) 0.371 (p ¼ 0.012) 0.376 (p ¼ 0.011)
Figure 2. Correlation of chemerin with SQ fat (a) and HOMA-IR (b).
Discussion Despite the strong association between altered adiposity and PCOS, the precise link between the two and how adiposity is linked to insulin resistance are incompletely understood. Hormones secreted by adipocytes, termed adipocytokines or adipokines, are altered in women with PCOS and may be a signal that mediates abnormal metabolic and reproductive function. The purpose of this study was to better characterize two novel adipokines, chemerin and omentin. While these adipokines have been studied in adults with metabolic syndrome, diabetes, and insulin resistance before and after various interventions [8,11–14], there are few data about these adipokines in PCOS. Preliminary data in the literature have suggested that levels of omentin-1 are decreased and levels of chemerin are increased in women with PCOS [7,9]. There are no data to our knowledge, however, on how these novel adipokines are compared with other more established adipokines, leptin and adiponectin, in correlating with adiposity and insulin resistance in PCOS. Our major purpose was not to check whether omentin-1 and chemerin levels are decreased or elevated in women with PCOS. We selected a large group of well-characterized women with a large range of body masses to be able to find correlations with adiposity and insulin resistance, and to compare these findings with those of leptin and adiponectin. Nevertheless, we carried out an analysis of the differences in adipokine levels in a subgroup of non-obese women with PCOS and controls. In this analysis, we
found that omentin-1 levels were lower in PCOS, but chemerin was not significantly higher in the entire PCOS group or the nonobese PCOS group. This finding is interesting in that chemerin appeared to correlate better than any other single adipokine with fat mass and insulin resistance. In the non-obese PCOS group, while we confirmed that adiponectin was lower in women with PCOS, leptin was higher. This is different from our previous data with weight-matched groups [3], but is not inconsistent with other reports [5]. The heterogeneity in adiposity and hyperandrogenism of different population of women with PCOS who have been studied may explain the inconsistent results regarding the levels of leptin in PCOS [15]. In a recent study, serum chemerin levels were increased in women with PCOS compared with weight-matched controls [7]. The increase in chemerin persisted when the obese (BMI425) PCOS group was compared with the obese control group, suggesting that obesity is not the only determining factor. In a different study, both serum chemerin and omental adipose chemerin were significantly higher in women with PCOS compared with age- and weight-matched controls [16]. Ex vivo treatment showed that chemerin synthesis and production was increased by insulin and decreased by metformin, suggesting that chemerin may be a link between hyperinsulinemia and PCOS. Chemerin absolute levels were also numerically different in the recent study [7] and what we report here, although our levels are more compatible with many other reports in non-PCOS populations [8,11]. Thus, heterogeneity in assay conditions between studies may be confounding the findings. Nevertheless, our report stresses the correlations with adiposity and insulin resistance. Here, chemerin correlated significantly with BMI, subcutaneous fat mass, and HOMA-IR. In this regard, chemerin was the single best correlate of these parameters, and rivaled that of the L/A ratio. Of interest, although omentin-1 levels were lower in PCOS, serum omentin did not correlate with any parameter, including a lack of correlation with the other adipokines. This may relate to the fact that omentin-1 is the product of the stromal vasculature in adipose tissue, rather than from adipocytes per se. Chemerin was the only adipokine tested to be positively associated with all three measures of adiposity and insulin resistance in PCOS. This finding is consistent with prior studies in both the PCOS and non-PCOS populations, which show chemerin to be positively associated with glucose response, insulin resistance, metabolic syndrome, and coronary artery disease [7,8,11]. As chemerin is a chemo-attractant adipokine with inflammatory properties, chemerin may be one of the most important links between adiposity and insulin resistance, and thus a good clinical marker for metabolic dysfunction. However, serum levels may not always reflect these changes as levels are determined by both the type and the abundance of adipose tissue, which by nature can be heterogeneous. In contrast, our findings on omentin-1 were completely negative. Serum omentin-1 levels had no association with markers of abnormal adiposity or insulin resistance in the groups tested, perhaps due to its origin of production as discussed above. Omentin-1 levels have been reported to be negatively associated with PCOS in some studies, but not others [5,7,10,11]. Therefore,
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omentin-1 is unlikely to be a good marker for PCOS or its associated metabolic dysfunction. In conclusion, we report that chemerin is a novel adipocytokine that appears to be an important physiological modulator of metabolic dysfunction in PCOS and is the single best correlate of adiposity and insulin resistance in women with PCOS, even though levels are not consistently elevated. More studies in the future will be needed to determine whether chemerin has clinical utility and to uncover differences in different phenotypes of PCOS which may help explain heterogeneity in the data.
Acknowledgements The authors would like to thank Jolene Lalas and Luz Sanabria from the Department of OBGYN, Columbia University for their assistance in patient recruitment and data collection. All parties consent to acknowledgement.
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Gynecol Endocrinol Downloaded from informahealthcare.com by Universitaet Zuerich on 12/31/14 For personal use only.
Declaration of interest The authors report no declarations of interest. The authors would like to thank The Endocrine Fellows Foundation for providing the financial support for endocrine assays.
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