Differential Gene Expression Profile in Omental Adipose Tissue in Women with Polycystic Ovary Syndrome

Cortón, Marta; Botella-Carretero, José I.; Benguría, Alberto; Villuendas, Gemma; Zaballos, Ángel; Millán, José L. San; Escobar-Morreale, Héctor F.; Peral, Belén

doi:10.1210/jc.2006-1665

Cited by 161 publications

(129 citation statements)

References 56 publications

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“…In contrast, a recent study found that adipose 11b-HSD1 was increased in women suffering from PCOS compared with healthy controls. 34 Two other studies have failed to show any polymorphisms in the HSD11B1 gene, and our results do not indicate reduced adipose cortisol production. 35,36 These results are not in line with our findings, possibly because of differences in study populations and methodology.…”

Section: Discussionsupporting

confidence: 46%

Expression of 11β-hydroxysteroid dehydrogenase 1 and 2 in subcutaneous adipose tissue of lean and obese women with and without polycystic ovary syndrome

et al. 2009

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Objective: To investigate the expression of 11b-hydroxysteroid dehydrogenase (11b-HSD) type 1 and 2 and hexose-6-phosphate dehydrogenase (H6PDH) mRNA in subcutaneous abdominal tissue from lean and obese women with and without polycystic ovary syndrome (PCOS), and to investigate the association between these enzymes and different measures of insulin sensitivity. Design: Cross-sectional study. Subjects: A total of 60 women, 36 women with PCOS, 17 lean (lean PCOS, LP) and 19 obese (obese PCOS, OP) and 24 age-and weight-matched control women, 8 lean (lean controls, LC) and 16 obese (obese controls, OC). Subcutaneous adipose tissue was collected from the abdomen. Peripheral insulin sensitivity was assessed by the euglycemic hyperinsulinemic clamp and determined as glucose disposal rate and insulin sensitivity index. Whole-body insulin sensitivity was calculated using homeostasis model assessment insulin resistance index. Body composition was evaluated by dual X-ray absorptiometry. Adipose mRNA expression of leptin and adiponectin were determined by real-time PCR. Results: Polycystic ovary syndrome (Po0.05) and obesity (Po0.05) were independently associated with increased expression of 11b-HSD1 mRNA. The subgroups LP and OC had increased 11b-HSD1 and 11b-HSD2 mRNA expression compared with LC (Po0.05, Po0.05). There were no effects of PCOS or obesity on11b-HSD2 or H6PDH mRNA expression. Decreased peripheral insulin sensitivity (Po0.001) and increased upper body fat distribution (Po0.01) were associated with increased expression of 11b-HSD1, but neither 11b-HSD2 nor H6PDH. Conclusion: Polycystic ovary syndrome and obesity are independently associated with increased expression of 11b-HSD1. This may lead to increased conversion of cortisone to cortisol in the peripheral adipose tissue and subsequently increased glucocorticoid activity. Decreased peripheral insulin sensitivity and central obesity was associated with increased expression of 11b-HSD1.

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Section: Discussionsupporting

confidence: 46%

Expression of 11β-hydroxysteroid dehydrogenase 1 and 2 in subcutaneous adipose tissue of lean and obese women with and without polycystic ovary syndrome

et al. 2009

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“…Another limitation is that only adipose tissue biopsies from one anatomical location were available for this study. Recently, genomic and proteomic profiling studies of morbidly obese PCOS omental adipose tissue have revealed changes in components of several biological pathways (34,35). Hence, there might be differences in the inflammatory status of visceral adipose tissue in women with PCOS (36).…”

Section: Discussionmentioning

confidence: 99%

Expression of the CD11c gene in subcutaneous adipose tissue is associated with cytokine level and insulin resistance in women with polycystic ovary syndrome

Tao

Zhao

et al. 2012

European Journal of Endocrinology

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Objective: Alterations in the phenotypes of macrophages in adipose tissue play a key role in inflammation and insulin resistance (IR). The phenotypes of macrophages in subcutaneous adipose tissue (SAT) and the relationship between proinflammation markers and IR in women with polycystic ovary syndrome (PCOS) remain unclear. The objectives of this study are to characterize the gene expression of macrophage markers and cytokines in the SAT of PCOS women and to estimate their relationships with circulating levels of cytokines and IR. Methods: The cross-sectional study involves 16 PCOS women and 18 normal control women. Cytokines and macrophage markers in the circulation and SAT were determined using ELISA, quantitative PCR, or immunofluorescence staining. IR was estimated using the homeostasis model assessment (HOMA-IR). Results: The gene expression levels of CD11c along with TNFa and leptin in SAT remained significantly higher in PCOS women than in normal women (P!0.05). However, no significant differences were found in CD68 mRNA expression in SAT between women with and without PCOS (PO0.05). Furthermore, CD11c mRNA abundance provided a stronger contribution to models predicting serum levels of TNFa (sTNFa) than did CD68 mRNA abundance. Lastly, increased sTNFa was associated with increased HOMA-IR in PCOS women, and this association was independent of both overall and visceral adiposity. Conclusion: The high expression level of CD11c mRNA in SAT was proved to be an important feature in PCOS women. Furthermore, CD11c mRNA abundance made a stronger contribution to models predicting sTNFa in which existing proinflammatory properties might significantly contribute to the pathogenesis of IR in PCOS women.

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“…Page 20 of 41 A c c e p t e d M a n u s c r i p t 20 As reported above, it is well known that ghrelin levels are negatively associated with obesity and positively with the insulin resistance state (Cortón et al, 2007;Shiiya et al, 2002).…”

Section: Ghrelin and The Polycystic Ovary Syndromementioning

confidence: 99%

“…Insulin resistance is very common in women with PCOS, particularly in the presence of obesity, and there is strong evidence this metabolic disorder, often associated with compensatory hyperinsulinemia, may play a triggering role in the pathophysiology of ovarian and adrenal hyperandrogenism, through different mechanisms described in detail elsewhere (Ehrmann 2005). Hyperandrogenism, in turn, may contribute to the generation of insulin resistance through the stimulation of lipolysis, and therefore the increased blood availability of FFA, and specific changes in muscle morphology, by increasing less insulin sensitive type 2 muscle fibers and decreasing the density of capillaries and glycogen content (Cortón et al, 2007). In addition, androgen excess may favor the enlargement of the visceral adipose tissue, which directly worsens insulin sensitivity.…”

Section: Ghrelin and The Polycystic Ovary Syndromementioning

confidence: 99%

Ghrelin and reproductive disorders

Repaci

Gambineri

Pagotto

et al. 2011

Molecular and Cellular Endocrinology

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Ghrelin is an important factor involved in most of the metabolic and hormonal signals which adapt the reproductive functions in conditions of altered energy balance. Moreover, the coordinated role of leptin and ghrelin appears in fact to have a specific role in the regulation of puberty. Systemic action of ghrelin on the reproductive axis involves the control of the hypothalamic-pituitary-gondal axis. In addition, it has been shown that ghrelin may directly act at a gonadal level in both females and males. Available data also demonstrate that sex steroid hormones and gonadotropins may in turn regulate the gonadal effect of ghrelin, as documented by studies performed in females with the polycystic ovary syndrome and in hypogonadal men. Notably, recent studies also confirm a potentially important role for ghrelin in fetal and neonatal energy balance, and specifically in allowing fetal adaptation to an adverse intrauterine environment.

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Differential Gene Expression Profile in Omental Adipose Tissue in Women with Polycystic Ovary Syndrome

Cited by 161 publications

References 56 publications

Expression of 11β-hydroxysteroid dehydrogenase 1 and 2 in subcutaneous adipose tissue of lean and obese women with and without polycystic ovary syndrome

Expression of 11β-hydroxysteroid dehydrogenase 1 and 2 in subcutaneous adipose tissue of lean and obese women with and without polycystic ovary syndrome

Expression of the CD11c gene in subcutaneous adipose tissue is associated with cytokine level and insulin resistance in women with polycystic ovary syndrome

Ghrelin and reproductive disorders

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