Serum Pigment Epithelium-Derived Factor Is Elevated in Women with Polycystic Ovary Syndrome and Correlates with Insulin Resistance

Yang, Sen; Li, Qifu; Zhong, Li; Song, Ying; Tian, Bo; Cheng, Qingfeng; Qing, Hua; Xia, Wei; Luo, Mei; Mei, Mei

doi:10.1210/jc.2010-2140

Cited by 41 publications

(43 citation statements)

References 26 publications

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“…Data from our group on circulating PEDF levels reported no difference between obese women with PCOS and age-and BMI-matched controls (Lecke et al 2013a), in accordance with a previous study with obese PCOS patients (Joham et al 2012). In normal-weight PCOS Chinese women, higher PEDF values were associated with insulin resistance (Yang et al 2011) and ultra-sensitive CRP (Cheng et al 2013). Recently, we have reported that PEDF mRNA in SC adipose tissue of PCOS women was similar to that found in age-and BMI-matched controls.…”

Section: Visfatinsupporting

confidence: 90%

Adipose tissue dysfunction, adipokines, and low-grade chronic inflammation in polycystic ovary syndrome

Spritzer¹,

Lecke²,

Satler³

et al. 2015

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Polycystic ovary syndrome (PCOS), a complex condition that affects women of reproductive age, is characterized by ovulatory dysfunction and androgen excess. Women with PCOS present higher prevalence of obesity, central adiposity, and dyslipidemia, and face increased risk of type 2 diabetes. PCOS is closely linked to functional derangements in adipose tissue. Adipocytes seem to be prone to hypertrophy when exposed to androgen excess, as experienced by women with PCOS, and both adipose tissue hypertrophy and hyperandrogenism are related to insulin resistance. Hypertrophic adipocytes are more susceptible to inflammation, apoptosis, fibrosis, and release of free fatty acids. Disturbed secretion of adipokines may also impact the pathophysiology of PCOS through their influence on metabolism and on sex steroid secretion. Chronic low-grade inflammation in PCOS is also related to hyperandrogenism and to the hypertrophy of adipocytes, causing compression phenomena in the stromal vessels, leading to adipose tissue hypoperfusion and altered secretion of cytokines. Lifestyle changes are the first-line intervention for reducing metabolic risks in PCOS and the addition of an insulin-sensitizing drug might be required. Nevertheless, there is not sufficient evidence in favor of any specific pharmacologic therapies to directly oppose inflammation. Further studies are warranted to identify an adipokine that could serve as an indirect marker of adipocyte production in PCOS, representing a reliable sign of metabolic alteration in this syndrome.

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Section: Visfatinsupporting

confidence: 90%

Adipose tissue dysfunction, adipokines, and low-grade chronic inflammation in polycystic ovary syndrome

Spritzer¹,

Lecke²,

Satler³

et al. 2015

Reproduction

258

206

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“…Insulin resistance is associated with elevated plasma PEDF in humans (32,38), and PEDF causes glucose intolerance and insulin resistance in cultured cells and mice (5,13,20). Fasting blood glucose and insulin were similar in WT and PEDF-aP2 mice (Table 2), and adipose-specific PEDF overexpression did not significantly affect glucose tolerance (Fig.…”

Section: Resultsmentioning

confidence: 91%

“…Much less is known regarding the antiangiogenic factors secreted locally and the role they play in the regulation of angiogenesis in expanding adipose tissue. PEDF is a major endogenous inhibitor of angiogenesis, circulating levels of PEDF are tightly correlated with obesity (25,26,30,32,37,38), and adipocytes are a major source of PEDF (13,20). Studies of human primary adipocytes have demonstrated that PEDF secretion is eightfold greater than adiponectin secretion and 140-fold greater than VEGF secretion (20).…”

Section: Discussionmentioning

confidence: 99%

Augmented expression and secretion of adipose-derived pigment epithelium-derived factor does not alter local angiogenesis or contribute to the development of systemic metabolic derangements

Lakeland

Borg

Matzaris

et al. 2014

American Journal of Physiology-Endocrinology and Metabolism

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Lakeland TV, Borg ML, Matzaris M, Abdelkader A, Evans RG, Watt MJ. Augmented expression and secretion of adipose-derived pigment epithelium-derived factor does not alter local angiogenesis or contribute to the development of systemic metabolic derangements. Am J Physiol Endocrinol Metab 306: E1367-E1377, 2014. First published April 23, 2014; doi:10.1152/ajpendo.00046.2014.-Impaired coupling of adipose tissue expansion and vascularization is proposed to lead to adipocyte hypoxia and inflammation, which in turn contributes to systemic metabolic derangements. Pigment epithelium-derived factor (PEDF) is a powerful antiangiogenic factor that is secreted by adipocytes, elevated in obesity, and implicated in the development of insulin resistance. We explored the angiogenic and metabolic role of adipose-derived PEDF through in vivo studies of mice with overexpression of PEDF in adipocytes (PEDF-aP2). PEDF expression in white adipocytes and PEDF secretion from adipose tissue was increased in transgenic mice, but circulating levels of PEDF were not increased. Overexpression of PEDF did not alter vascularization, the partial pressure of O 2, cellular hypoxia, or gene expression of inflammatory markers in adipose tissue. Energy expenditure and metabolic substrate utilization, body mass, and adiposity were not altered in PEDF-aP2 mice. Whole body glycemic control was normal as assessed by glucose and insulin tolerance tests, and adipocyte-specific glucose uptake was unaffected by PEDF overexpression. Adipocyte lipolysis was increased in PEDF-aP2 mice and associated with increased adipose triglyceride lipase and decreased perilipin 1 expression. Experiments conducted in mice rendered obese by high-fat feeding showed no differences between PEDF-aP2 and wild-type mice for body mass, adiposity, whole body energy expenditure, glucose tolerance, or adipose tissue oxygenation. Together, these data indicate that adipocyte-generated PEDF enhances lipolysis but question the role of PEDF as a major antiangiogenic or proinflammatory mediator in adipose tissue in vivo. pigment epithelium-derived factor; lipolysis; obesity; insulin sensitivity ADIPOCYTES SECRETE PROTEINS AND METABOLITES that play major roles in the regulation of metabolism, appetite, energy expenditure, and inflammation.

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“…It was performed 6-8 day after oral glucose tolerance test as described previously [18][19][20]: after fasting overnight, subjects were admitted to the hospital, where iv cannulas were placed in both arms for insulin and glucose infusion and for blood sampling. A priming dose of insulin was given followed by an infusion (120mIU/ m 2 /min) of short-acting human insulin (Lilly, Humulin, USA) for 120 min.…”

Section: Hyperinsulinemic-euglycemic Clampmentioning

confidence: 99%

Dysregulation of glucose metabolism even in Chinese PCOS women with normal glucose tolerance

2012

Endocr J

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Polycystic ovary syndrome (Pcos) is the most common endocrine disturbance in women of reproductive age [1]. It is important to prevent glucose metabolic disorder of PCOS as early as possible since more than 40% of PCOS women might develop impaired glucose tolerance or type 2 diabetes [2,3]. However, the early interventions of improving glucose metabolism were seldom adopted because the glucose levels of PCOS women were normal before developing impaired glucose tolerance.Insulin resistance is a common feature of PCOS [4][5][6], and when insulin secretion from β cell becomes inadequate in relation to insulin resistance, impaired glucose tolerance and type 2 diabetes will eventually develop [7,8]. However, few studies investigated glucose levels distribution of PCOS before developing impaired glu- In conclusion, insulin resistance and dysregulation of glucose metabolism were common in Chinese PCOS women with normal glucose tolerance. BMI ≥ 25.545kg/m 2 indicated impaired β cell function in PCOS women with normal glucose tolerance.Key words: Polycystic ovary syndrome, β cell function, Insulin resistance, Normal glucose tolerance cose tolerance and the association between β cell function and PCOS is still disputable. Especially for PCOS women with normal glucose tolerance, lots of studies (in particular from North American) found impaired β cell function [4,8,9], while other studies reported preserved β cell function [7,10,11]. The difference of β cell function in previous studies might be related to failing to take into account the effect of confounding variables, such as ethnicity [12], medication history [13], a family history of type 2 diabetes [14]. In addition, the methods of evaluating β cell function could vary between different studies, with important consequences on metabolic results.To clarify the necessity of preventing glucose metabolic disorder of PCOS as early as possible and to understand why PCOS women with normal glucose tolerance show such heterogeneous levels of β cell function, the present study investigated glucose levels distribution, insulin sensitivity by euglycemic-hyperinsulinemic clamp and β cell function by homeostatic model assessment (HOMA)-β index after adjusting insulin sensitivity (HOMA-βad index) in Chinese PCOS women with normal glucose tolerance after excluding the effect of

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Serum Pigment Epithelium-Derived Factor Is Elevated in Women with Polycystic Ovary Syndrome and Correlates with Insulin Resistance

Abstract: The serum PEDF level is elevated in women with PCOS and is associated with IR. PEDF may play a role in the pathogenesis of IR in PCOS.

Cited by 41 publications

References 26 publications

Adipose tissue dysfunction, adipokines, and low-grade chronic inflammation in polycystic ovary syndrome

Adipose tissue dysfunction, adipokines, and low-grade chronic inflammation in polycystic ovary syndrome

Augmented expression and secretion of adipose-derived pigment epithelium-derived factor does not alter local angiogenesis or contribute to the development of systemic metabolic derangements

Dysregulation of glucose metabolism even in Chinese PCOS women with normal glucose tolerance

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