Hyperglycemia-induced oxidative stress is independent of excess abdominal adiposity in normal-weight women with polycystic ovary syndrome

The pathophysiology of Polycystic Ovary Syndrome (PCOS) is quite complex and different mechanisms could contribute to hyperandrogenism and anovulation, which are the main features of the syndrome. Obesity and insulin-resistance are claimed as the principal factors contributing to the clinical presentation; in normal weight PCOS either, increased visceral adipose tissue has been described. However, their role is still debated, as debated are the biochemical markers linked to obesity per se. Oxidative stress (OS) and low-grade inflammation (LGI) have recently been a matter of researcher attention; they can influence each other in a reciprocal vicious cycle. In this review, we summarize the main mechanism of radical generation and the link with LGI. Furthermore, we discuss papers in favor or against the role of obesity as the first pathogenetic factor, and show how OS itself, on the contrary, can induce obesity and insulin resistance; in particular, the role of GH-IGF-1 axis is highlighted. Finally, the possible consequences on vitamin D synthesis and activation on the immune system are briefly discussed. This review intends to underline the key role of oxidative stress and low-grade inflammation in the physiopathology of PCOS, they can cause or worsen obesity, insulin-resistance, vitamin D deficiency, and immune dyscrasia, suggesting an inverse interaction to what is usually considered.

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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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Overweight and Obesity in Polycystic Ovary Syndrome: Association with Inflammation, Oxidative Stress and Dyslipidemia

British Journal Of Nutrition ◽

10.1017/s0007114521003585 ◽

2021 ◽

pp. 1-22

Author(s):

Iva M. Perovic Blagojevic ◽

Jelena Z. Vekic ◽

Djuro P. Macut ◽

Svetlana D. Ignjatovic ◽

Milica M. Miljkovic-Trailovic ◽

...

Keyword(s):

Oxidative Stress ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Normal Weight ◽

Overweight And Obesity ◽

Paraoxonase 1 ◽

Pon1 Activity ◽

Ovary Syndrome ◽

Lipoprotein Subclasses ◽

Ldl Particles

Abstract Objective: Polycystic ovary syndrome (PCOS) is associated with altered lipid profile and increased small, dense LDL particles (sdLDL). Considering that paraoxonase 1 (PON1) is an anti-oxidative enzyme located on high-density lipoprotein (HDL) particles, the aim of this study was to investigate the connection between oxidative stress (OS) and PON1 activity with lipoprotein subclasses in PCOS depending on obesity. Methods: In 115 PCOS patients lipoprotein subclasses distributions were determined by gradient gel electrophoresis. OS status was assessed by total oxidative status (TOS), advanced oxidation protein products (AOPP), malondialdehyde (MDA), prooxidant-antioxidant balance (PAB), total antioxidant status (TAS) and superoxide dismutase (SOD) and PON1 activity. Results: Overweight/obese PCOS patients (n=55) had increased OS compared to normal weight patients (n=60). In addition, overweight/obese group had lower HDL size and higher proportion of HDL 3a subclasses (P<0.05). PAB was in negative correlation with HDL 2a (P<0.001), whereas MDA and SOD correlated positively with HDL 3 subclasses (P<0.05). Serum PON1 activity was positively associated with proportions of PON1 activity on HDL 2b (P<0.05) and 2a (P<0.01), but negatively with the proportion on HDL 3 particles (P<0.01). LDL B phenotype patients had increased TAS, SOD and PON1 activity on HDL 2b, but decreased PON1 activity on HDL 3 subclasses. Conclusion: OS is associated with altered lipoprotein subclasses distribution in PCOS patients. Obesity in PCOS affects the profile of HDL subclasses, reflected through the reduced proportion of PON1 activity on HDL 3 subclasses in the presence of sdLDL particles.

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