Decreased soluble leptin receptor levels in women with polycystic ovary syndrome

Objective: Polycystic ovary syndrome (PCOS) is associated with insulin resistance and a high incidence of obesity. Leptin, the product of the ob gene, is involved in the regulation of energy balance and obesity and circulates in both free and bound forms. The soluble leptin receptor (sOB-R) is the most important leptin-binding protein, thus influencing the biologically active free leptin level. Design: We assessed the correlation of metabolic and endocrine parameters with leptin and sOB-R levels in 122 PCOS women (aged 27 ± 5.7 years) and 81 healthy controls (aged 25 ± 4.0 years). Methods: Leptin and sOB-R levels were measured using ELISA kits. In addition, anthropometric variables, body fat and endocrine parameters were evaluated and a glucose tolerance test performed to assess indices of insulin resistance and glucose metabolism. Results: In PCOS patients, no correlation was found between leptin or sOB-R and parameters of hyper-androgenism. However, as expected, body mass index (BMI), body fat, waist circumference and indices of insulin resistance were significantly correlated with leptin in PCOS subjects and controls. In a subgroup analysis of lean, overweight and obese PCOS patients, significant differences were found in leptin (29.7 ± 20.7 vs 45.4 ± 25.0 vs 67.7 ± 28.8 ng/ml, P < 0.0001) and sOB-R (8.0 ± 3.4 vs 6.4 ± 2.5 vs 5.7 ± 2.3 ng/ml, P < 0.05). Compared with BMI-matched controls, lean PCOS patients had lower sOB-R levels (8.0 ± 3.4 vs 12.7 ± 4.7 ng/ml, P < 0.0001) and higher free leptin indices (4.5 ± 3.9 vs 2.8 ± 2.2, P = 0.0285). Conclusion: Taking into account that low sOB-R levels supposedly compensate diminished leptin action, PCOS per se might cause leptin resistance.

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Leptin and soluble leptin receptor levels in patients with the polycystic ovary syndrome: influence of metabolic and endocrine parameters

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/s-2005-862981 ◽

2005 ◽

Vol 113 (S 1) ◽

Author(s):

S Hahn ◽

U Haselhorst ◽

A Schütz ◽

S Tan ◽

BL Herrmann ◽

...

Keyword(s):

Polycystic Ovary Syndrome ◽

Leptin Receptor ◽

Polycystic Ovary ◽

Ovary Syndrome ◽

Soluble Leptin Receptor ◽

Endocrine Parameters

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Serum soluble leptin receptor levels and free leptin index in women with polycystic ovary syndrome: relationship to insulin resistance and androgens

Fertility and Sterility ◽

10.1016/j.fertnstert.2005.10.038 ◽

2006 ◽

Vol 85 (5) ◽

pp. 1441-1447 ◽

Cited By ~ 29

Author(s):

Vicken P. Sepilian ◽

John R. Crochet ◽

Manubai Nagamani

Keyword(s):

Insulin Resistance ◽

Polycystic Ovary Syndrome ◽

Leptin Receptor ◽

Polycystic Ovary ◽

Ovary Syndrome ◽

Soluble Leptin Receptor

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Central-to-peripheral fat ratio, but not peripheral body fat, is related to insulin resistance and androgen markers in polycystic ovary syndrome

Gynecological Endocrinology ◽

10.1080/09513590903015528 ◽

2009 ◽

pp. 1-6 ◽

Cited By ~ 1

Author(s):

Amelio Godoy-Matos ◽

Fernanda Vaisman ◽

Aline Pedrosa ◽

Maria Farias ◽

Laura Maria Mendonca ◽

...

Keyword(s):

Insulin Resistance ◽

Polycystic Ovary Syndrome ◽

Body Fat ◽

Polycystic Ovary ◽

Ovary Syndrome

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Leptin as well as Free Leptin Receptor Is Associated with Polycystic Ovary Syndrome in Young Women

International Journal of Endocrinology ◽

10.1155/2015/927805 ◽

2015 ◽

Vol 2015 ◽

pp. 1-10 ◽

Cited By ~ 7

Author(s):

Nasser M. Rizk ◽

Elham Sharif

Keyword(s):

Insulin Resistance ◽

Leptin Receptor ◽

Polycystic Ovary ◽

Cross Sectional Study ◽

Compensatory Mechanism ◽

Ovary Syndrome ◽

Cross Sectional ◽

Soluble Leptin Receptor ◽

Median Level ◽

Male Sex

Background and Aim. Leptin has two forms in the circulation: free and bound forms. The soluble leptin receptor (sOB-R) circulates in the blood and can bind to leptin. The aim of this study is to assess the concentrations of the leptin and the sOB-R in PCOS and its relation to adiposity, insulin resistance, and androgens.Methods. A cross-sectional study included 78 female students aged 17–25 years. Fasting serum leptin and sOB-R concentrations were measured. The anthropometric variables and the hormonal profile such as insulin, female and male sex hormones, and prolactin were assessed.Results. In PCOS, leptin level (ng/ml) and free leptin index (FLI) increased significantly while sOB-R (ng/ml) significantly decreased compared to control subjects. In age-matched subjects, obese PCOS had increased leptin level in ng/ml (median level with interquartile levels) of 45.67 (41.98–48.04) and decreased sOB-R in ng/ml 11.47 (7.59–16.44) compared to lean PCOS 16.97 (10.60–45.55) for leptin and 16.62 (11.61–17.96) for sOB-R withpvalues 0.013 and 0.042, respectively. However, body mass index (BMI) is significantly correlated with leptin and s-OBR, while no significant correlations with parameters of insulin resistance were detected.Conclusion. PCOS is associated with hyperleptinemia and increased free leptin index. Decreased sOB-R could be a compensatory mechanism for the defective action of leptin.

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Analysis of Body Mass Index, Waist Circumference, and Body Fat in Predicting Insulin Resistance of Polycystic Ovary Syndrome

Advanced Science Letters ◽

10.1166/asl.2017.9403 ◽

2017 ◽

Vol 23 (7) ◽

pp. 6807-6810

Author(s):

Achmad Kemal Harzif ◽

Dwiyanarsi Yusuf ◽

Melisa Silvia ◽

Budi Wiweko ◽

Andon Hestiantoro

Keyword(s):

Insulin Resistance ◽

Body Mass Index ◽

Waist Circumference ◽

Polycystic Ovary Syndrome ◽

Body Mass ◽

Body Fat ◽

Polycystic Ovary ◽

Ovary Syndrome

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Body fat and insulin resistance independently predict increased serum C-reactive protein in hyperandrogenic women with polycystic ovary syndrome

Acta Endocrinologica ◽

10.1530/eje-09-0379 ◽

2009 ◽

Vol 161 (5) ◽

pp. 737-745 ◽

Cited By ~ 29

Author(s):

Flavia Tosi ◽

Romolo Dorizzi ◽

Roberto Castello ◽

Claudio Maffeis ◽

Giovanna Spiazzi ◽

...

Keyword(s):

Insulin Resistance ◽

Insulin Sensitivity ◽

Polycystic Ovary Syndrome ◽

Body Fat ◽

Polycystic Ovary ◽

C Reactive Protein ◽

Androgen Excess ◽

Ovary Syndrome ◽

Reactive Protein ◽

Hs Crp

ObjectiveIncreased serum C-reactive protein (CRP), an independent predictor of coronary heart disease, was reported in women with polycystic ovary syndrome (PCOS). It remains unclear whether this finding is due to the association between PCOS and either insulin resistance, obesity, or androgen excess, which are all common features of this condition. The aims of this study were to assess whether increased serum CRP is a specific feature of PCOS and to investigate the mechanisms underlying this association.Design and methodsSerum high-sensitivity CRP (hs-CRP) was measured in 86 hyperandrogenic women (age 21.6±4.2 years, body mass index (BMI) 23.6±3.5 kg/m2), 50 with PCOS and 36 with idiopathic hyperandrogenism (HA). Thirty-five BMI-matched healthy women were also studied as controls. In these subjects, endocrine and metabolic profiles were assessed. In all hyperandrogenic subjects and 14 controls, insulin sensitivity was measured by the glucose clamp technique. Body fat was measured by bioelectrical impedance.ResultsHs-CRP concentrations were higher in PCOS women (3.43±2.01 mg/l) than in HA subjects and healthy women (2.43±1.04, P<0.005; and 2.75±0.86 mg/l, P<0.05 respectively versus PCOS). In multiple regression analyses, increased serum hs-CRP was independently predicted by higher body fat and lower insulin sensitivity. However, in lean women, serum-free testosterone was an additional, negative, predictive variable.ConclusionsPCOS is accompanied by a low-grade chronic inflammation. Body fat appears the main determining factor of this finding, which is only partly explained by insulin resistance. At least in lean women, androgen excess per se seems to play an additional, possibly protective, role in this association.

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Serum Leptin Levels in Women with Polycystic Ovary Syndrome: The Role of Insulin Resistance/ Hyperinsulinemia1

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.82.6.4028 ◽

1997 ◽

Vol 82 (6) ◽

pp. 1692-1696

Author(s):

G. A. Laughlin ◽

A. J. Morales ◽

S. S. C. Yen

Keyword(s):

Insulin Resistance ◽

Polycystic Ovary Syndrome ◽

Body Fat ◽

Polycystic Ovary ◽

Pulse Amplitude ◽

Percent Body Fat ◽

Ovary Syndrome ◽

Serum Leptin ◽

Insulin Levels

Abstract Polycystic ovary syndrome (PCOS) is associated with chronic anovulation, hyperandrogenemia, insulin resistance (IR)/hyperinsulinemia, and a high incidence of obesity. Thus, PCOS serves as a useful model to assess the role of IR and chronic endogenous insulin excess on leptin levels. Thirty-three PCOS and 32 normally cycling (NC) women of similar body mass index (BMI) were studied. Insulin sensitivity (SI) was assessed by rapid ivGTT in a subset of 28 PCOS and 29 NC subjects; percent body fat was determined by dual-energy x-ray absorptiometry (DEXA) in 14 PCOS and 17 NC. Fasting (0800 h) and 24-h mean hourly insulin levels were 2-fold higher (P < 0.0001), and SI was 50% lower (P = 0.005) in PCOS than in NC, while serum androstenedione (A), testosterone (T), 17-α hydroxyprogesterone (17OHP), and estrone (E1) levels were elevated (P < 0.0001), and sex hormone-binding globulin (SHBG) levels were decreased (P < 0.01). Twenty-four hour LH pulse frequency, mean pulse amplitude, and mean LH levels were elevated in PCOS (P < 0.001) as compared with NC. Serum leptin levels for PCOS (24.1 ± 2.6 ng/mL) did not differ from NC (21.5 ± 3.5 ng/mL) and were positively correlated with BMI (r = 0.81) and percent body fat (r = 0.91) for the two groups (both P < 0.0001). Leptin levels for PCOS and NC correlated positively with fasting and 24-h mean insulin levels (r = 0.81, P < 0.0001 for both PCOS and NC) and negatively with SI and SHBG levels. Leptin concentrations for PCOS, but not NC, correlated positively with 24-h mean glucose levels and inversely with 24-h mean LH levels and 24-h mean LH pulse amplitude. Leptin levels were not correlated with estrogen or androgen levels for either PCOS or NC, although leptin levels were positively related to the ratios of E1/SHBG and E2/SHBG for both PCOS and NC and to the ratio of T/SHBG for PCOS only. In stepwise multivariate regression with forward selection, only 24-h mean insulin levels contributed significantly (P < 0.01) to leptin levels independent of BMI and percent body fat for both PCOS and NC. Given this relationship and the presence of 2-fold higher 24-h mean insulin levels in PCOS, the expected elevation of leptin levels in PCOS was not found. This paradox may be explained by the presence of adipocyte IR specific to PCOS, which may negate the stimulatory impact of hyperinsulinemia on leptin secretion, a proposition requiring further study.

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Retinol-binding protein 4 levels are elevated in polycystic ovary syndrome women with obesity and impaired glucose metabolism

Acta Endocrinologica ◽

10.1530/eje-07-0143 ◽

2007 ◽

Vol 157 (2) ◽

pp. 201-207 ◽

Cited By ~ 28

Author(s):

Susanne Hahn ◽

Manuel Backhaus ◽

Martina Broecker-Preuss ◽

Susanne Tan ◽

Tiina Dietz ◽

...

Keyword(s):

Insulin Resistance ◽

Glucose Metabolism ◽

Polycystic Ovary Syndrome ◽

Body Fat ◽

Polycystic Ovary ◽

Retinol Binding Protein ◽

Healthy Controls ◽

Impaired Glucose Metabolism ◽

Ovary Syndrome ◽

Retinol Binding Protein 4

Objective: Insulin resistance and obesity are common features of the polycystic ovary syndrome (PCOS). Retinol-binding protein 4 (RBP4), a new fat-derived adipokine, has been described to be elevated in obesity and type 2 diabetes. The aim of the present study was to investigate whether serum RBP4 levels are correlated with metabolic parameters, indices of insulin resistance, and endocrine variables in German PCOS women. Design: We assessed the correlation between metabolic and endocrine parameters with RBP4 levels in 200 PCOS patients and 64 healthy controls. Methods: Serum RBP4 was measured by enzyme-linked immunosorbent assay (Immundiagnostik AG, Bensheim, Germany). In addition, anthropometric variables, clinical signs of hyperandrogenism, and body fat were evaluated, and a glucose tolerance test was performed to assess parameters of insulin resistance and glucose metabolism. Results: Taking the entire PCOS cohort, RBP4 levels were positively correlated with body mass index (BMI), body fat, waist circumference, fasting glucose, and area under the curve for glucose (all P<0.05), but not with indices of insulin resistance. On the other hand, PCOS women with impaired glucose metabolism had higher RBP4 levels than PCOS women with normal glucose metabolism (median 30.6, range 23.3–73.9 versus median 26.3, range 6.4–61.4, P<0.05). Furthermore, no differences were found in RBP4 levels between lean PCOS women and BMI-matched healthy controls. Conclusion: In German PCOS women, serum RBP4 levels are associated with obesity and parameters of glucose metabolism but not with PCOS per se.

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