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Adiponectin Levels in Women with Polycystic Ovary Syndrome

Department of Molecular and Clinical Endocrinology and Oncology (F.O., T.C., A.C., G.L.), University "Federico II," 80131 Naples; Chair of Obstetrics and Gynecology (S.P., F.Z.), University of Catanzaro, 88100 Catanzaro; and Department of Internal Medicine, Department of Medical and Surgical Sciences (G.M., R.M., C.P., R.V.), University of Padova, 35128 Padova, Italy

Address all correspondence and requests for reprints to: Dr. Francesco Orio, Jr., Via Giovanni Santoro n.14, 84123 Salerno, Italy. E-mail: f.orio{at}tin.it.

	Abstract

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Serum adiponectin levels were evaluated in 60 women with polycystic ovary syndrome (PCOS), 30 normal-weighted and 30 obese women, and 60 healthy women age and body mass index (BMI) matched with the patients. The homeostasis model assessment (HOMA) score was also calculated. Both in PCOS and controls, serum adiponectin levels were significantly (P < 0.05) lower in obese than normal-weight women, without any difference between PCOS and controls. The HOMA score was significantly (P < 0.05) higher in obese than normal-weight women both in PCOS and controls; additionally, the HOMA score was significantly (P < 0.05) higher in normal-weight PCOS than normal-weight controls. Both in PCOS and controls, adiponectin levels were significantly correlated with BMI (r = -0.51, P < 0.01 in PCOS; r = -0.45, P < 0.01 in controls) and HOMA values (r = -0.39, P < 0.05 in PCOS; r = -0.35, P < 0.05 in controls); HOMA was correlated with BMI (r = 0.51, P < 0.01 in PCOS, r = 0.61, P < 0.001 in controls). In conclusion, our results confirm that adiponectin concentrations change according to variations of fat mass. They further suggest that insulin sensitivity per se probably does not play any pivotal role in the control of adiponectin levels in PCOS women.

	Introduction

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POLYCYSTIC OVARY SYNDROME (PCOS) is one of the most common endocrine-metabolic diseases, affecting up to 10% of women of reproductive age (1, 2). Obesity is present in approximately 44% of women with PCOS, and it is characterized by central distribution of fat. In women with PCOS, hyperinsulinemia, dyslipidemia, and/or hypertension are highly dependent on obesity, which worsens the clinical presentation of PCOS (1, 3).

The adipose tissue not only stores a large quantity of fat as an energy source (4) but also expresses a variety of genes of secretory proteins (5, 6, 7, 8, 9). The human apM1 gene has been recently discovered, and it is exclusively expressed in white adipose tissue (10). The product of this gene is called adiponectin, a 244-amino acid protein with high structural homology to collagen VIII, X, complement C1q, and TNF (11, 12). Adiponectin expression is increased by peroxisome proliferator-activated receptor agonists (13, 14).

Although the physiological role of adiponectin still has to be clarified, recent findings have indicated that it may be a kind of matrix protein with potential antiatherogenic and antiinflammatory effects (15, 16, 17, 18). Because adiponectin is a fat cell product, secreted into the circulating blood, it might be responsible for the metabolic and neuroendocrine derangements characteristic of obesity and obesity-related disease, such as PCOS.

Despite adiponectin being secreted only from adipose tissue, its plasma levels in obese subjects are, paradoxically, lower than in nonose subjects (19). Reductions of body weight increase adiponectin concentrations (20), suggesting that adiponectin expression is down-regulated by adipose tissue (21).

Moreover, serum adiponectin concentrations correlate inversely with the severity of insulin resistance (22, 23, 24) and plasma levels of low-density lipoprotein cholesterol, and triglycerides (21, 25, 26, 27, 28).

At the present no data are available on adiponectin levels in women with PCOS. In this view the aim of the present study was to evaluate serum adiponectin levels in a population of normal-weight and obese PCOS women.

	Subjects and Methods

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All the procedures used in this study were in accordance with the guidelines of the Helsinki Declaration on Human Experimentations. The study was approved by local ethical committee; the purpose of the protocol was explained to both the patients and control women, and written informed consent was obtained from them before beginning the study.

Subjects

Sixty women with PCOS, 30 normal-weight [body mass index (BMI), 18–25 kg/m²], and 30 obese (BMI, >30 kg/m²) were enrolled for the study. The diagnosis of PCOS was made using the following criteria: 1) anovulatory infertility and normal serum FSH levels (normal range, 1.0–10.0 IU/liter), and 2) at least two of the following features: hirsutism (Ferriman and Gallwey score, >8); elevated serum androgen levels [total testosterone (T), >2 nmol/liter], and/or androstenedione (A) greater than 15 nmol/liter, and/or dehydroepiandrosterone sulfate (DHEA-S) greater than 10 µmol/liter); LH/FSH ratio above 2; and polycystic ovaries identified by transvaginal ultrasonography (TV-USG) examination (29, 30).

Sixty healthy women matched for age and BMI with the patients agreed to participate to this study as controls. All controls were evaluated by a medical history, physical and pelvic examination, and complete blood chemistry. Women with a menstrual cycle less than 26 d or more than 30 d were excluded. The normal ovulatory state was confirmed by TV-USG and plasma progesterone (P) assay during the luteal phase of the cycle.

Exclusion criteria for all subjects were pregnancy, hypothyroidism, hyperprolactinemia, Cushing’s syndrome, congenital adrenal hyperplasia, current or previous (within the last 6 months) use of oral contraceptives, glucocorticoids, antiandrogens, ovulation induction agents, antidiabetic and antiobesity drugs, or other hormonal drugs. None of the patients was affected by neoplastic, metabolic, and cardiovascular disorder or other concurrent relevant medical illness. All subjects were nonsmokers, and none drank alcoholic beverages.

Study protocol

Patients were studied during early follicular phase (second to fifth day) of the spontaneous or P-induced menstrual cycle. Blood samples were collected after an overnight fasting from all subjects for biochemical and hormonal determinations.

All subjects underwent TV-USG and anthropometric measurements. In particular, in each woman weight and height were measured to calculate BMI. Waist to hip circumference ratio was also measured (29).

Biochemical and hormonal analysis

Plasma LH, FSH, 17ß-estradiol (E₂), P, 17OH-progesterone (17OH-P), T, A, DHEA-S, prolactin (PRL), SHBG, glucose, insulin, and adiponectin levels were evaluated in each subjects in duplicate. LH, FSH, E₂, P, T, A, DHEA-S, 17OH-P, and PRL were measured by specific RIA as previously described (30, 31). SHBG was measured using an immunoradiometric assay (30). Plasma glucose was determined by the glucose oxidase method (30), and serum insulin was measured by a solid-phase chemiluminescent enzyme immunoassay (30). Adiponectin was measured in serum using a commercially available RIA kit (Linco Research, Inc., St. Charles, MO) in which ¹²⁵I-labeled murine adiponectin and a multispecies adiponectin rabbit antiserum was used to determine the level of adiponectin in serum by the double-antibody/PEG. Adiponectin standards were prepared using recombinant human adiponectin with a sensitivity of 1 ng/ml and intraassay and interassay coefficient of variation of 3.1% and 5%, respectively. The free androgen index was calculated using the following formula: T (nmol/liter)/SHBG (nmol/liter) x 100 (32). The estimate of insulin resistance by homeostasis model assessment (HOMA) score was also calculated in all subjects as described by Matthews et al. (33).

Statistical analysis

The statistical analysis was performed using the SPSS 9.0 (SPSS, Inc., Chicago, IL) package by the unpaired t test. The Pearson’s correlation coefficients were calculated. Data are presented as mean ± SE. Statistical significance was set at 5%.

	Results

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Table 1 shows anthropometric, biochemical, and endocrine data in PCOS and control women, according to BMI. As expected, LH, P, 17OH-P, T, A, DHEA-S, SHBG, and insulin differ in PCOS, compared with controls (Table 1). Additionally, insulin levels were lower (P < 0.05) in normal-weight than obese women of both groups (Table 1).

View larger version (11K): [in this window] [in a new window]   Figure 1. Adiponectin levels in 60 PCOS and 60 healthy women, grouped according to BMI in 30 subjects/group.

View larger version (11K): [in this window] [in a new window]   Figure 2. HOMA values in 60 PCOS and 60 healthy women, grouped according to BMI in 30 subjects/group.

	Discussion

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Adiponectin is probably one of the most important adipocytokines of the adipose tissue (25). It is highly expressed and actively secreted by adipocytes (34); it is abundantly present in the human circulation and displays a variety of functions, including antiatherogenic, antiinflammatory, and insulin-sensitizing properties (15, 35, 36).

This is the first study evaluating serum adiponectin concentrations in obese and normal-weight PCOS women. Our data confirm that obese women have adiponectin levels significantly lower than normal-weight healthy controls (37, 38). In addition, fasting serum adiponectin levels in patients with PCOS were comparable to those observed in control women matched for age and BMI. Obese PCOS women also exhibit reduced adiponectin levels when compared with normal-weight women with PCOS. Lastly, adiponectin levels were inversely correlated with BMI both in PCOS and healthy women.

Plasma adiponectin concentrations were decreased in insulin-resistant obese (19) and type 2 diabetic patients (39). PCOS is characterized by insulin resistance, which may lead to major metabolic consequences with an increased risk of developing type 2 diabetes in respect to the general female population (40). PCOS patients often display an increased basal insulin level, likely caused by an increased insulin secretion and a reduced hepatic insulin clearance (40); impairment of peripheral insulin-stimulated glucose utilization is also present. It has been shown that these abnormalities are independent of obesity, which, when present, displays a further worsening effect on insulin sensitivity (41).

In the present study, insulin levels were higher and insulin sensitivity, as assessed by HOMA, lower in normal-weight PCOS group than in controls; serum adiponectin concentrations did not differ between the two groups. Therefore, the high degree of insulin resistance in women with PCOS (42) does not influence (is unlikely to modify) adiponectin levels, despite the evidence that adiponectin levels have been widely recognized to be decreased in an insulin resistant state (22). The link between adiponectin and insulin sensitivity was further enforced by the observation that this adipocytokine is able to stimulate glucose utilization (43) and reduce the hepatic glucose production (44). Furthermore, adiponectin expression in rodents was shown to be highly affected by changes in adiposity and insulin sensitivity (45).

The low adiponectin level in obesity probably is due to its down-regulation by the increased adipose tissue. An amelioration of insulin sensitivity, which occurs during reduction of body weight (46), is likely linked to this phenomenon because the increase of insulin sensitivity could be associated with the increase of adiponectin levels. In fact, adiponectin has been shown to be suppressed in states of insulin resistance, such as type 2 diabetes (22) and obesity (47). Additionally, in a large series of Japanese subjects (48) and adult Pima Indians (22), adiponectin levels were negatively related to the indices of insulin resistance even after the adjustment for age and BMI; in Pima Indian children, these levels decreased with increasing adiposity, without any correlation with obesity-induced insulin resistance (36).

It is worth noting, however, that normal-weight PCOS women, who have increased insulin secretion, compared with normal-weight controls, have normal adiponectin levels, ruling out a relevant role of insulin on adiponectin secretion. Thus, our data suggest that adiponectin variations result mainly by changes in the adipose tissue more than by changes of insulin levels and/or insulin sensitivity.

As further support of our clinical data, recent studies in adiponectin knockout mice report a substantial lack of effects on insulin sensitivity, measured by a hyperinsulinemic-euglycemic clamp (49). However, when adiponectin knockout mice were infected with adenovirus producing full-length adiponectin, insulin sensitivity increased (50). All these data taken together suggest that the complex puzzle of adiponectin regulation at the adipose tissue is still to be fully elucidated.

In conclusion, our results further confirm that adiponectin concentrations change according to variations of fat mass in healthy women as well as women with PCOS. They also suggest that insulin sensitivity per se is unlikely to play a pivotal role in the control of adiponectin levels in PCOS women.

	Footnotes

 
Abbreviations: 17OH-P, 17OH-progesterone; A, androstenedione; BMI, body mass index; DHEA-S, dehydroepiandrosterone sulfate; E₂, 17ß-estradiol; HOMA, homeostasis model assessment; P, progesterone; PCOS, polycystic ovary syndrome; PRL, prolactin; T, testosterone; TV-USG, transvaginal ultrasonography.

Received December 26, 2002.

Accepted February 24, 2003.

	References

Top Abstract Introduction Subjects and Methods Results Discussion References

 

1. Carmina E, Lobo RA 1999 Polycystic ovary syndrome (PCOS): arguably the most common endocrinopathy is associated with significant morbidity in women. J Clin Endocrinol Metab 84:1897–1899[Free Full Text]
2. Legro RS 2001 Polycystic ovary syndrome: the new millennium. Mol Cell Endocrinol 184:87–93[CrossRef][Medline]
3. Elting MW, Korsen TJM, Shoemaker J 2001 Obesity, rather than menstrual cycle pattern or follicle cohort size, determines hyperinsulinemia, dyslipidemia and hypertension in ageing women with polycystic ovary syndrome. Clin Endocrinol 55:767–776[CrossRef][Medline]
4. Trayhurn P, Beattie JH 2001 Physiological role of adipose tissue: white adipose tissue as an endocrine and secretory organ. Proc Nutr Soc 60:329–339[Medline]
5. Maeda K, Okubo K, Shimomura I, Mizuno K, Matsuzawa K 1997 Analysis of an expression profile of genes in the human adipose tissue. Gene 190:227–235[CrossRef][Medline]
6. Koutnikowa H, Auwerx J 2001 Regulation of adipocyte differentiation. Ann Med 33:556–561[Medline]
7. McTernan PG, McTernan CL, Chetty R, Jenner K, Fisher FM, Lauren MN, Crocker J, Barnett AH, Kumar S 2002 Increased resistin gene and protein expression in human abdominal adipose tissue. J Clin Endocrinol Metab 87:2407–2410[Abstract/Free Full Text]
8. Wasim A, Haque WA, Shimomura I, Matsuzawa Y, Garg A 2002 Serum adiponectin and leptin levels in patients with lipodystrophies. J Clin Endocrinol Metab 87:2395–2398[Abstract/Free Full Text]
9. Matsuzawa Y, Funahashi T, Nakamura T 2002 Molecular mechanism of metabolic syndrome X: contribution of adipocytokines, adipocyte-derived bioactive substances. Ann N Y Acad Sci 892:146–154
10. Saito K, Tobe T, Minoshima S, Asakawa S, Sumiya J, Yoda M, Nakano Y, Shimizu N, Tomita M 1999 Organization of the gene for gelatin-binding protein (GBP28). Gene 229:67–73[CrossRef][Medline]
11. Halleux CM, Takahashi M, Delporte ML, Detry R, Funahashi T, Matsuzawa Y, Brichard SM 2001 Secretion of adiponectin and regulation of apM1 gene expression in human visceral adipose tissue. Biochem Biophys Res Commun 288:1102–1007[CrossRef][Medline]
12. Takahashi M, Arita Y, Yamagata K, Matsuzawa Y, Okutomi K, Horie M, Shimomura I, Hotta K, Kuriyama H, Kihara S, Nakamura T, Yamashita S, Funahashi T, Matsuzawa Y 2000 Genomic structure and mutations in adipose-specific gene, adiponectin. Int J Obes 24:861–868[CrossRef][Medline]
13. Maeda N, Takahashi M, Funahashi T, Kihara S, Nishizawa H, Kishida K, Nagaretani H, Matsuda M, Komuro R, Ouchi N, Kuriyama H, Hotta K, Nakamura T, Shimomura I, Matsuzawa Y 2001 PPARy ligands increase expression and plasma concentrations of adiponectin, an adipose-derived protein. Diabetes 50:2094–2099[Abstract/Free Full Text]
14. Yang WS, Leng CY, Wu TJ, Tanaka S, Funahashi T, Matsuzawa Y, Wang JP, Chen CL, Tai TY, Chuang LM 2002 Synthetic peroxisome proliferator-activated receptor agonist, rosiglitazone, increases plasma levels of adiponectin in type 2 diabetic patients. Diabetes Care 25:376–380[Abstract/Free Full Text]
15. Ouchi N, Kihara S, Arita Y, Maeda K, Kuriyama H, Okamoto Y, Hotta K, Nishida M, Takahashi M, Nakamura T, Yamashita S, Funahashi T, Matsuzawa Y 1999 Novel modulator for endothelial adhesion molecules adipocyte-derived plasma protein adiponectin. Circulation 100:2473–2476[Abstract/Free Full Text]
16. Matsubara M, Maruoka S, Katayose S 2002 Decreased plasma adiponectin concentrations in women with dyslipidemia. J Clin Endocrinol Metab 87:2764–2769[Abstract/Free Full Text]
17. Arita Y, Kihara S, Ouchi N, Maeda K, Kuriyama H, Okamoto Y, Kumada M, Hotta K, Nishida M, Takahashi M, Nakamura T, Shimomura I, Muraguchi M, Ohmoto Y, Funahashi T, Matsuzawa Y 2002 Adipocyte-derived plasma protein adiponectin acts as a platelet-derived growth factor-BB-binding protein and regulates growth factor-induced common postreceptor signal in vascular smooth muscle cell. Circulation 105:2893–2898[Abstract/Free Full Text]
18. Yang WS, Lee WJ, Funahashi T, Tanaka S, Matsazawa Y, Chao CL, Chen CL, Tai TY, Chuang LM 2001 Weight reduction increases plasma levels of an adipose-derived anti-inflammatory protein, adiponectin. J Clin Endocrinol Metab 86:3815–3819[Abstract/Free Full Text]
19. Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa JI, Hotta K, Shimomura I, Nakamura T, Miyaoka K, Kuriyama H, Nishida M, Yamashita S, Okubo K, Matsubara K, Muraguchi M, Ohmoto Y, Funahashi T, Matsuzawa Y 1999 Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun 257:79–83[CrossRef][Medline]
20. Yang WS, Lee WJ, Funahashi T, Tanaka S, Matsazawa Y, Chao CL, Chen CL, Tai TY, Chuang LM 2001 Weight reduction increases plasma levels of an adipose-derived anti-inflammatory protein, adiponectin. J Clin Endocrinol Metabol 86:3815–3819
21. Matsubara M, Maruoka S, Katayose S 2002 Decreased plasma adiponectin concentrations in women with dyslipidemia. J Clin Endocrinol Metab 87:2764–2769
22. Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley RE, Tateranni A 2001 Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab 86:1930–1935[Abstract/Free Full Text]
23. Kubota N, Terauchi Y, Yamauchi T, Kubota T, Moroi M, Matsui J, Eto K, Yamashita T, Kamon J, Satoh H, Yano W, Froge P, Nagai R, Rimura S, Kadiwaki T, Noda T 2002 Disruption of adiponectin causes insulin resistance and neointimal formation. J Biol Chem 277:25863–25866[Abstract/Free Full Text]
24. Kondo H, Shimomura I, Matsukawa Y, Takahashi M, Matsuda M, Ouchi N, Kihara S, Kanamoto T, Sumitsuji S, Funahashi T, Matsuzawa Y 2002 Association of adiponectin mutation with type 2 diabetes. Diabetes 51:2325–2328[Abstract/Free Full Text]
25. Berg AH, Combs TP, Scherer PE 2002 ACRP30/adiponectin: an adipokine regulating glucose and lipid metabolism. Trends Endocrinol Metab 13:84–89[CrossRef][Medline]
26. Comuzzie AG, Funahashi T, Sonnenberg G, Martin LJ, Jacob HJ, Kwitek Black AE, Maas D, Takahashi M, Kihara S, Tanaka S, Matsuzawa Y, Blangero J, Cohen D, Kissebah A 2001 The genetic basis of plasma variation in adiponectin, a global endophenotype for obesity and the metabolic syndrome. J Clin Endocrinol Metab 86:4321–4325[Abstract/Free Full Text]
27. Menzaghi C, Ercolino T, Di Paola R, Berg AH, Warram JH, Scherer PE, Trischitta V, Doria A 2002 A haplotype at the adiponectine locus is associated with obesity and other features of the insuline resistance syndrome. Diabetes 51:2306–2312[Abstract/Free Full Text]
28. Kazumi T, Kawaguchi A, Sakai K, Hirano T, Yoshino G 2002 Young men with high-normal blood pressure have lower serum adiponectin, smaller LDL size, and higher elevated heart rate than those with optimal blood pressure. Diabetes Care 25:971–976[Abstract/Free Full Text]
29. Orio Jr F, Lucidi P, Palomba S, Tauchmanovà L, Cascella T, Russo T, Zullo F, Colao A, Lombardi G, De Feo P 2003 Circulating ghrelin concentrations in the polycystic ovary syndrome. J Clin Endocrinol Metab 88:942–945[Abstract]
30. Orio Jr F, Palomba S, Di Biase S, Colao A, Tauchmanovà L, Savastano S, Labella D, Russo T, Zullo F, Lombardi G 2003 Homocysteine levels and C677T polymorphism of methylenetetrahydrofolate reductase in women with polycystic ovary syndrome. J Clin Endocrinol Metab 88:673–679[Abstract/Free Full Text]
31. Orio Jr F, Palomba S, Colao A, Tenuta M, Dentico C, Peretta M, Lombardi G, Nappi C, Orio F 2001 Growth hormone secretion after baclofen administration in different phases of the menstrual cycle in healthy women. Horm Res 55:131–136[CrossRef][Medline]
32. Morley JE, Patrick P, Perry III HM 2002 Evaluation of assays available to measure free testosterone. Metabolism 5:554–559
33. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC 1985 Homeostasis model assessment: insulin resistance and ß-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419[CrossRef][Medline]
34. Tsao TS, Lodish HF, Fruebis J 2002 ACRP30, a new hormone controlling fat and glucose metabolism. Eur J Pharmacol 440:213–221[CrossRef][Medline]
35. Ouchi N, Kihara S, Arita Y, Okamoto Y, Maeda K, Kuriyama H, Hotta K, Nishida M, Takahashi M, Muraguchi M, Ohmoto Y, Nakamura T, Yamashita S, Funahashi T, Matsuzawa Y 2000 Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF-kappaB signaling through a cAMP-dependent pathway. Circulation 102:1296–1301[Abstract/Free Full Text]
36. Stefan N, Bunt JC, Salbe AD, Funahashi T, Matsuzawa Y, Tataranni PA 2002 Plasma adiponectin concentrations in children: relationships with obesity and insulinemia. J Clin Endocrinol Metab 87:4652–4656[Abstract/Free Full Text]
37. Yang WS, Lee WJ, Funahashi T, Tanaka S, Matsazawa Y, Chao CL, Chen CL, Tai TY, Chuang LM 2001 Weight reduction increases plasma levels of an adipose-derived anti-inflammatory protein, adiponectin. J Clin Endocrinol Metab 86:3815–3819
38. Berg AH, Combs TP, Scherer PE 2002 ACRP30/adiponectin: an adipokine regulating glucose and lipid metabolism. Trends Endocrinol Metab 13:84–89
39. Hotta K, Funahashin T, Arita Y, Takahashi M, Matsuda M, Okamoto Y, Iwahashi H, Kuriyama H, Ouchi N, Maeda K, Nishida M, Kihara S, Sakai N, Nakajima T, Hasegawa K, Muraguchi M, Ohmoto Y, Nakamura T, Yamashita S, Hanafusa T, Matsuzawa Y 2000 Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol 20:1595–1599[Abstract/Free Full Text]
40. Legro RS, Kunselman AR, Dodson WC, Dunaif A 1999 Prevalence and predictors of risk for type 2 diabetes mellitus and impaired glucose tolerance in polycystic ovary syndrome: a prospective, controlled study in 254 affected women. J Clin Endocrinol Metab 84:165–169[Abstract/Free Full Text]
41. O’Meara NM, Blackman JD, Ehrmann DA, Barnes RB, Jaspan JB, Rosenfield RL, Polonsky KS 1993 Defects in beta-cell function in functional ovarian hyperandrogenism. J Clin Endocrinol Metab 76:1241–1247[Abstract]
42. Dunaif A 1997 Insuline resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr Rev 18:774–800[Abstract/Free Full Text]
43. Yamauchi T, Kamon J, Minokoshi Y, Ito Y, Waki H, Uchida S, Yamashita S, Noda M, Kita S, Ueki K, Eto K, Akanuma Y, Froguel P, Foufelle F, Ferre P, Carling D, Kimura S, Nagai R, Kahn BB, Kadowaki T 2002 Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med 8:1288–1295[CrossRef][Medline]
44. Combs TP, Berg AH, Obici S, Scherer PE, Rossetti L 2001 Endogenous glucose production is inhibited by the adipose-derived protein Acrp-30. J Cin Invest 108:1875–1881[CrossRef][Medline]
45. Milan G, Granzotto M, Scarda A, Calcagno A, Pagano C, Federspil G, Vettor R 2002 Resistin and adiponectin expression in visceral fat of obese rats: effect of weight loss. Obes Res 10:1095–1103[Medline]
46. Houmard JA, Tanner CJ, Yu C, Cunningham PG, Pories WJ, MacDonald KG, Shulman GI 2002 Effect of weight loss on insulin sensitivity and intramuscular long-chain fatty acyl-CoAs in morbidly obese subjects. Diabetes 51:2959–2963[Abstract/Free Full Text]
47. Hu E, Liang P, Spiegelman BM 1996 AdipoQ is a novel adipose-specific gene dysregulated in obesity. J Biol Chem 271:10697–10703[Abstract/Free Full Text]
48. Yamamoto Y, Hirose H, Saito I, Tomita M, Taniyama M, Matsubara K, Okazaki Y, Ishii T, Nishikai K, Saruta T 2002 Correlation of the adipocyte-derived protein adiponectin with insulin resistance index and serum high-density lipoprotein-cholesterol, independent of body mass index, in the Japanese population. Clin Sci 103:137–142[Medline]
49. Ma K, Cabrero A, Saha PK, Kojima H, Li L, Chang BH, Paul A, Chan L 2002 Increased beta-oxidation but no insulin resistance or glucose intolerance in mice lacking adiponectin. J Biol Chem 277:34658–34661[Abstract/Free Full Text]
50. Maeda N, Shimomura I, Kishida K, Nishizawa H, Matsuda M, Nagaretani H, Furuyama N, Kondo H, Takahashi M, Arita Y, Komuro R, Ouchi N, Kihara S, Tochino Y, Okutomi K, Horie M, Takeda S, Aoyama T, Funahashi T, Matsuzawa Y 2002 Diet-induced insulin resistance in mice lacking adiponectin/ACRP30. Nat Med 8:731–737[CrossRef][Medline]

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				M. Yilmaz, N. Bukan, R. Ersoy, A. Karakoc, I. Yetkin, G. Ayvaz, N. Cakir, and M. Arslan Glucose intolerance, insulin resistance and cardiovascular risk factors in first degree relatives of women with polycystic ovary syndrome Hum. Reprod., September 1, 2005; 20(9): 2414 - 2420. [Abstract] [Full Text] [PDF]

				E Carmina, F Orio, S Palomba, T Cascella, R A Longo, A M Colao, G Lombardi, and R A Lobo Evidence for altered adipocyte function in polycystic ovary syndrome Eur. J. Endocrinol., March 1, 2005; 152(3): 389 - 394. [Abstract] [Full Text] [PDF]

				V. Sepilian and M. Nagamani Adiponectin Levels in Women With Polycystic Ovary Syndrome and Severe Insulin Resistance Reproductive Sciences, February 1, 2005; 12(2): 129 - 134. [Abstract] [PDF]

				N. Xita, I. Georgiou, A. Chatzikyriakidou, M. Vounatsou, G.-P. Papassotiriou, I. Papassotiriou, and A. Tsatsoulis Effect of Adiponectin Gene Polymorphisms on Circulating Adiponectin and Insulin Resistance Indexes in Women with Polycystic Ovary Syndrome Clin. Chem., February 1, 2005; 51(2): 416 - 423. [Abstract] [Full Text] [PDF]

				J. P. Thyfault, E. M. Hedberg, R. M. Anchan, O. P. Thorne, C. M. Isler, E. R. Newton, G. L. Dohm, and J. E. deVente Gestational Diabetes is Associated with Depressed Adiponectin Levels Reproductive Sciences, January 1, 2005; 12(1): 41 - 45. [Abstract] [PDF]

				F. Orio Jr., S. Palomba, T. Cascella, S. Di Biase, F. Manguso, L. Tauchmanova, L. G. Nardo, D. Labella, S. Savastano, T. Russo, et al. The Increase of Leukocytes as a New Putative Marker of Low-Grade Chronic Inflammation and Early Cardiovascular Risk in Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., January 1, 2005; 90(1): 2 - 5. [Abstract] [Full Text] [PDF]

				F. Orio Jr., S. Palomba, T. Cascella, S. Di Biase, D. Labella, T. Russo, S. Savastano, F. Zullo, A. Colao, R. Vettor, et al. Lack of an Association between Peroxisome Proliferator-Activated Receptor-{gamma} Gene Pro12Ala Polymorphism and Adiponectin Levels in the Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., October 1, 2004; 89(10): 5110 - 5115. [Abstract] [Full Text] [PDF]

				F. Orio Jr., S. Palomba, T. Cascella, B. De Simone, S. Di Biase, T. Russo, D. Labella, F. Zullo, G. Lombardi, and A. Colao Early Impairment of Endothelial Structure and Function in Young Normal-Weight Women with Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., September 1, 2004; 89(9): 4588 - 4593. [Abstract] [Full Text] [PDF]

				A. Bottner, J. Kratzsch, G. Muller, T. M. Kapellen, S. Bluher, E. Keller, M. Bluher, and W. Kiess Gender Differences of Adiponectin Levels Develop during the Progression of Puberty and Are Related to Serum Androgen Levels J. Clin. Endocrinol. Metab., August 1, 2004; 89(8): 4053 - 4061. [Abstract] [Full Text] [PDF]

				D. Panidis, A. Kourtis, A. Kukuvitis, D. Farmakiotis, N. Xita, I. Georgiou, and A. Tsatsoulis Association of the T45G polymorphism in exon 2 of the adiponectin gene with polycystic ovary syndrome: role of {Delta}4-androstenedione Hum. Reprod., August 1, 2004; 19(8): 1728 - 1733. [Abstract] [Full Text] [PDF]

				M. A. Williams, C. Qiu, M. Muy-Rivera, S. Vadachkoria, T. Song, and D. A. Luthy Plasma Adiponectin Concentrations in Early Pregnancy and Subsequent Risk of Gestational Diabetes Mellitus J. Clin. Endocrinol. Metab., May 1, 2004; 89(5): 2306 - 2311. [Abstract] [Full Text] [PDF]

				J. Hoffstedt, E. Arvidsson, E. Sjolin, K. Wahlen, and P. Arner Adipose Tissue Adiponectin Production and Adiponectin Serum Concentration in Human Obesity and Insulin Resistance J. Clin. Endocrinol. Metab., March 1, 2004; 89(3): 1391 - 1396. [Abstract] [Full Text] [PDF]

				W. A. Hsueh and D. Bruemmer Peroxisome Proliferator-Activated Receptor {gamma}: Implications for Cardiovascular Disease Hypertension, February 1, 2004; 43(2): 297 - 305. [Abstract] [Full Text] [PDF]

				F. Orio, S. Palomba, F. Zullo, A. Colao, and G. Lombardi Are serum adiponectin levels really reduced in obese women with polycystic ovary syndrome? Hum. Reprod., January 1, 2004; 19(1): 215 - 215. [Full Text] [PDF]

				D. Panidis, D. Farmakiotis, A. Kourtis, and D. Rousso Reply: adiponectin levels in women with polycystic ovary syndrome reflect increased adiposity rather than insulin resistance Hum. Reprod., January 1, 2004; 19(1): 215 - 216. [Full Text] [PDF]

				F. Orio Jr., G. Matarese, S. Di Biase, S. Palomba, D. Labella, V. Sanna, S. Savastano, F. Zullo, A. Colao, and G. Lombardi Exon 6 and 2 Peroxisome Proliferator-Activated Receptor-{gamma} Polymorphisms in Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., December 1, 2003; 88(12): 5887 - 5892. [Abstract] [Full Text] [PDF]

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