Increased regulated on activation, normal T-cell expressed and secreted levels and cysteine–cysteine chemokine receptor 5 upregulation in omental adipose tissue and peripheral blood mononuclear cells are associated with testosterone level and insulin resistance in polycystic ovary syndrome

Polycystic ovary syndrome is a highly frequent reproductive-endocrine disorder affecting up to 8–10% of women worldwide at reproductive age. Although its etiology is not fully understood, evidence suggests that insulin resistance, with or without compensatory hyperinsulinemia, and hyperandrogenism are very common features of the polycystic ovary syndrome phenotype. Dysfunctional white adipose tissue has been identified as a major contributing factor for insulin resistance in polycystic ovary syndrome. Environmental (e.g., chronodisruption) and genetic/epigenetic factors may also play relevant roles in syndrome development. Overweight and/or obesity are very common in women with polycystic ovary syndrome, thus suggesting that some polycystic ovary syndrome and metabolic syndrome female phenotypes share common characteristics. Sleep disturbances have been reported to double in women with PCOS and obstructive sleep apnea is a common feature in polycystic ovary syndrome patients. Maturation of the luteinizing hormone-releasing hormone secretion pattern in girls in puberty is closely related to changes in the sleep-wake cycle and could have relevance in the pathogenesis of polycystic ovary syndrome. This review article focuses on two main issues in the polycystic ovary syndrome-metabolic syndrome phenotype development: (a) the impact of androgen excess on white adipose tissue function and (b) the possible efficacy of adjuvant melatonin therapy to improve the chronobiologic profile in polycystic ovary syndrome-metabolic syndrome individuals. Genetic variants in melatonin receptor have been linked to increased risk of developing polycystic ovary syndrome, to impairments in insulin secretion, and to increased fasting glucose levels. Melatonin therapy may protect against several metabolic syndrome comorbidities in polycystic ovary syndrome and could be applied from the initial phases of patients’ treatment.

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Adiposity and metabolic dysfunction in polycystic ovary syndrome

Hormone Molecular Biology and Clinical Investigation ◽

10.1515/hmbci-2015-0008 ◽

2015 ◽

Vol 21 (2) ◽

Cited By ~ 7

Author(s):

Susan Sam

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Polycystic Ovary Syndrome ◽

Metabolic Disorders ◽

Polycystic Ovary ◽

Reproductive Age ◽

Metabolic Dysfunction ◽

Obese Women ◽

Ovary Syndrome ◽

Insulin Resistant

AbstractPolycystic ovary syndrome (PCOS) is the most common hormonal disorder among reproductive-age women and is associated with a high risk for metabolic disorders. Adiposity and insulin resistance are two prevalent conditions in PCOS and the likely culprits for the heightened metabolic risk. Up to 60% of women with PCOS are considered to be overweight or obese, and even among non-obese women with PCOS there is an increased accumulation of adipose tissue in abdominal depots. Insulin resistance in PCOS is unique and independent of obesity, as even non-obese women with this condition are frequently insulin resistant. However, obesity substantially aggravates the insulin resistance and the metabolic and reproductive abnormalities in women with PCOS. Recently, it has been shown that many aspects of adipose tissue function in PCOS are abnormal, and these abnormalities likely predispose to development of insulin resistance even in the absence of obesity. This review provides an overview of these abnormalities and their impact on development of metabolic disorders. At the end, an overview of the therapeutic options for management of adiposity and its complications in PCOS are discussed.

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The therapeutic effect of interleukin-22 in high androgen-induced polycystic ovary syndrome

Journal of Endocrinology ◽

10.1530/joe-19-0589 ◽

2020 ◽

Vol 245 (2) ◽

pp. 281-289 ◽

Cited By ~ 2

Author(s):

Xinyu Qi ◽

Chuyu Yun ◽

Baoying Liao ◽

Jie Qiao ◽

Yanli Pang

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Polycystic Ovary Syndrome ◽

White Adipose Tissue ◽

Polycystic Ovary ◽

Therapeutic Effects ◽

Ovary Syndrome ◽

Interleukin 22 ◽

Immune Factor ◽

Embryo Number

Polycystic ovary syndrome (PCOS) is a complex syndrome involving both endocrine and metabolic disorders. Gut microbiota and the intestinal immune factor IL-22 play an important role in the pathogenesis of PCOS. However, the therapeutic role of IL-22 in high androgen-induced PCOS mice is not clear. We aimed to determine the therapeutic effects of IL-22 on the DHEA-induced PCOS mouse model and to explore the possible mechanism of IL-22 in regulating hyperandrogenism-associated PCOS. Insulin resistance levels and ovarian functions were investigated in DHEA-induced PCOS mice with or without additional IL-22 treatment. We found that IL-22 could reverse insulin resistance, disturbed estrous cycle, abnormal ovary morphology, and decreased embryo number in DHEA mice. Mechanistically, IL-22 upregulated the browning of white adipose tissue in DHEA mice. This study demonstrated that IL-22-associated browning of white adipose tissue regulated insulin sensitivity and ovarian functions in PCOS, suggesting that IL-22 may be of value for the treatment of PCOS with a hyperandrogenism phenotype.

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Plasmatic and Intracellular Markers of Oxidative Stress in Normal Weight and Obese Patients with Polycystic Ovary Syndrome

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/s-0043-111241 ◽

2017 ◽

Vol 125 (08) ◽

pp. 506-513 ◽

Cited By ~ 3

Author(s):

Chantal Di Segni ◽

Andrea Silvestrini ◽

Romana Fato ◽

Christian Bergamini ◽

Francesco Guidi ◽

...

Keyword(s):

Oxidative Stress ◽

Insulin Resistance ◽

Polycystic Ovary Syndrome ◽

Mononuclear Cells ◽

Polycystic Ovary ◽

Gradient Centrifugation ◽

Normal Weight ◽

Model Assessment ◽

Obese Patients ◽

Ovary Syndrome

Abstract Introduction Insulin resistance (IR) is associated with polycystic ovary syndrome (PCOS). Oxidative stress (OS) is, in turn, related to IR. Studies in PCOS evidenced an increase in OS markers, but they are mainly performed in obese patients, while the complex picture of normal weight PCOS is still poorly investigated. Matherials and Methods To investigate OS in PCOS and relationship with hormonal and metabolic picture, we performed a case-control study in 2 PCOS groups: normal weight (N-PCOS, n=21, age 18–25 ys, mean±SEM BMI 20.7±0.2 kg/m2) and obese (OB-PCOS, n=15, 20–30 ys, BMI 32.8±1.1), compared with control groups matched for BMI: normal (N-C, n=10, 20–30 ys, BMI 21.6±0.9) and obese (OB-C, n=20, 21–31ys, BMI 36.8±1.0). Malondialdehyde (MDA) in blood plasma and peripheral mononuclear cells, obtained by density-gradient centrifugation, was assayed spectrophotometrically by TBARS assay. CoenzymeQ10 (CoQ10) in plasma and cells was assayed by HPLC. Plasma Total Antioxidant Capacity (TAC) was also measured by spectrophotometric method. Results PCOS patients exhibited higher Testosterone levels than controls, but OB-PCOS had highest HOMA (Homeostasis Model Assessment) index, suggesting marked insulin resistance. Despite plasma MDA levels were not significantly different (N-PCOS 3380±346.94 vs. N-C 7 120±541.66; OB-PCOS 5 517.5±853.9 vs. OB. 3 939.66±311.2 pmol/ml), intracellular MDA levels were significantly higher in N-PCOS than controls (mean 3 259±821.5 vs. 458±43.2 pmol/106/cells) and higher than OB-PCOS, although not significantly (1363.1±412.8 pmol/106/cells). Intracellular CoenzymeQ10 was higher in N-PCOS than in N-C, but the highest levels were found in OB-C. Conclusions Our data, while confirming the presence of OS in obese PCOS patients in agreement with literature, suggest that OS could be present also in normal weight PCOS, but it can be revealed in tissue rather than in plasma. The relationship with metabolic status remains to be established, but could be a physiopathological basis for antioxidant treatment in such patients.

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