scholarly journals Oxidative Stress in Response to Saturated Fat Ingestion Is Linked to Insulin Resistance and Hyperandrogenism in Polycystic Ovary Syndrome

2019 ◽  
Vol 104 (11) ◽  
pp. 5360-5371 ◽  
Author(s):  
Frank González ◽  
Robert V Considine ◽  
Ola A Abdelhadi ◽  
Anthony J Acton
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Protein Content ◽  
Polycystic Ovary ◽  
Saturated Fat ◽  
Ros Generation ◽  
Ovary Syndrome ◽  
Control Subjects ◽  
Androgen Secretion

Abstract Context Oxidative stress and insulin resistance are often present in polycystic ovary syndrome (PCOS). Objective We determined the effect of saturated fat ingestion on leukocytic reactive oxygen species (ROS) generation, p47phox expression, and circulating thiobarbituric acid–reactive substances (TBARS) in women with PCOS. Design Cross-sectional study. Setting Academic medical center. Patients Twenty women of reproductive age with PCOS (10 lean, 10 with obesity) and 19 ovulatory control subjects (10 lean, 9 with obesity). Main Outcome Measures ROS generation and p47phox mRNA and protein content were quantified in leukocytes, and TBARS was measured in plasma from blood drawn while the subjects were fasting and 2, 3, and 5 hours after saturated fat ingestion. Insulin sensitivity was derived from an oral glucose tolerance test (ISOGTT). Androgen secretion was assessed from blood drawn while the subjects were fasting and 24, 48, and 72 hours after human chorionic gonadotropin (HCG) administration. Results Regardless of weight class, women with PCOS exhibited lipid-induced increases in leukocytic ROS generation and p47phox mRNA and protein content as well as plasma TBARS compared with lean control subjects. Both PCOS groups exhibited lower ISOGTT and greater HCG-stimulated androgen secretion compared with control subjects. The ROS generation, p47phox, and TBARS responses were negatively correlated with ISOGTT and positively correlated with HCG-stimulated androgen secretion. Conclusion In PCOS, increases in ROS generation, p47phox gene expression, and circulating TBARS in response to saturated fat ingestion are independent of obesity. Circulating mononuclear cells and excess adipose tissue are separate and distinct contributors to oxidative stress in this disorder.

scholarly journals Saturated Fat Ingestion Promotes Lipopolysaccharide-Mediated Inflammation and Insulin Resistance in Polycystic Ovary Syndrome

2018 ◽  
Vol 104 (3) ◽  
pp. 934-946 ◽  
Author(s):  
Frank González ◽  
Robert V Considine ◽  
Ola A Abdelhadi ◽  
Anthony J Acton
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Protein Content ◽  
Polycystic Ovary ◽  
Saturated Fat ◽  
Cytokine Signaling ◽  
Oral Glucose ◽  
Ovary Syndrome ◽  
Control Subjects ◽  
Androgen Secretion

Abstract Context Inflammation and insulin resistance (IR) are often present in polycystic ovary syndrome (PCOS). Objective We determined the effect of saturated fat ingestion on circulating lipopolysaccharide (LPS) and mononuclear cell (MNC) toll-like receptor-4 (TLR-4) and suppressor of cytokine signaling-3 (SOCS-3) in women with PCOS. Design Cross-sectional study. Setting Academic medical center. Patients Nineteen reproductive-age women with PCOS (10 lean, 9 obese) and 19 ovulatory control subjects (10 lean, 9 obese). Main Outcome Measures LPS and TNFα levels were measured in plasma. TLR-4 and SOCS-3 mRNA and protein content were quantified in MNC from blood collected after fasting and 2, 3, and 5 hours after saturated fat ingestion. Insulin sensitivity was derived from an oral glucose tolerance test (ISOGTT). Androgen secretion was assessed from blood collected after fasting and 24, 48, and 72 hours after human chorionic gonadotropin (HCG) administration. Results Regardless of PCOS status, subjects who were obese had lipid-induced increases in circulating LPS and TLR-4 protein content compared with subjects who were lean. Lean and obese women with PCOS had lipid-induced increases in plasma TNFα and SOCS-3 mRNA and protein content compared with lean control subjects. Both PCOS groups had lower ISOGTT and greater HCG-stimulated androgen secretion compared with control subjects. The LPS and SOCS-3 responses were negatively correlated with ISOGTT and positively correlated with HCG-stimulated androgen secretion. Conclusion In PCOS, lipid-induced LPS-mediated inflammation through TLR-4 is associated with obesity and worsened by PCOS, whereas lipid-induced increases in SOCS-3 may represent an obesity-independent, TNFα-mediated mechanism of IR.

scholarly journals Inflammation Triggered by Saturated Fat Ingestion Is Linked to Insulin Resistance and Hyperandrogenism in Polycystic Ovary Syndrome

2020 ◽  
Vol 105 (6) ◽  
pp. e2152-e2167 ◽  
Author(s):  
Frank González ◽  
Robert V Considine ◽  
Ola A Abdelhadi ◽  
Anthony J Acton
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Saturated Fat ◽  
Oral Glucose ◽  
Weight Class ◽  
Ovary Syndrome ◽  
Control Subjects ◽  
Androgen Secretion

Abstract Context Inflammation and insulin resistance are often present in polycystic ovary syndrome (PCOS). Objective We determined the effect of saturated fat ingestion on mononuclear cell (MNC) nuclear factor-κB (NFκB) activation; NFκB, inhibitory-κBα (IκBα), and tumor necrosis factor-α (TNFα) gene expression; and circulating C-reactive protein (CRP) in women with PCOS. Design Cross-sectional study. Setting Academic medical center. Patients Twenty reproductive-age women with PCOS (10 lean, 10 with obesity) and 20 ovulatory controls (10 lean, 10 with obesity). Main Outcome Measures Activated NFκB, NFκB heterodimer subunits, IκBα and TNFα messenger ribonucleic acid content and NFκB p65 and IκBα protein content were quantified in mononuclear cells (MNC), and CRP was measured in plasma from blood drawn fasting and 2, 3, and 5 h after saturated fat ingestion. Insulin sensitivity was derived from oral glucose tolerance testing (ISOGTT). Androgen secretion was assessed from blood drawn fasting and 24, 48, and 72 h after human chorionic gonadotropin (HCG) administration. Results In response to saturated fat ingestion, women with PCOS regardless of weight class exhibited lipid-induced increases in activated NFκB, NFκB, and TNFα gene expression and plasma CRP and decreases in IκBα protein compared with lean control subjects. Both PCOS groups exhibited lower ISOGTT and greater HCG-stimulated androgen secretion compared with control subjects. Lipid-stimulated NFκB activation was negatively correlated with ISOGTT, and positively correlated with HCG-stimulated androgen secretion. Conclusion In PCOS, increases in NFκB activation and circulating CRP and decreases in IκBα protein following saturated fat ingestion are independent of obesity. Circulating MNC and excess adipose tissue are separate and distinct contributors to inflammation in this disorder.

scholarly journals Reactive Oxygen Species-Induced Oxidative Stress in the Development of Insulin Resistance and Hyperandrogenism in Polycystic Ovary Syndrome

2006 ◽  
Vol 91 (1) ◽  
pp. 336-340 ◽  
Author(s):  
Frank González ◽  
Neal S. Rote ◽  
Judi Minium ◽  
John P. Kirwan
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Reactive Oxygen Species ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Reactive Oxygen ◽  
Ros Generation ◽  
Oxygen Species ◽  
Ovary Syndrome ◽  
Percent Change

Abstract Context: Insulin resistance and chronic low level inflammation are often present in women with polycystic ovary syndrome (PCOS). Objective: The purpose of this study was to determine the effects of hyperglycemia on reactive oxygen species (ROS) generation from mononuclear cells (MNCs) in PCOS. Design: This was a prospective controlled study. Setting: The study was conducted at an academic medical center. Patients: The study population consisted of 16 women with PCOS (eight lean, eight obese) and 15 age- and body composition-matched controls (eight lean, seven obese). Main Outcome Measures: Insulin sensitivity was derived from a 2-h, 75-g oral glucose tolerance test (ISOGTT). ROS generation and p47phox protein expression were quantitated from MNCs obtained from blood drawn fasting and 2 h after glucose ingestion. Results: ISOGTT was lower in PCOS, compared with controls (3.1 ± 0.3 vs. 6.3 ± 0.9, P < 0.003). The percent change in ROS generation from MNCs was higher in lean and obese PCOS, compared with lean controls (138.8 ± 21.3 and 154.2 ± 49.1 vs. 0.6 ± 12.7, P < 0.003). The percent change in ROS generation from MNCs correlated positively with glucose area under the curve (r = 0.38, P < 0.05), and plasma levels of testosterone (r = 0.59, P < 0.002) and androstenedione (r = 0.50, P < 0.009). The percent change in p47phox from MNCs was also higher in lean and obese PCOS, compared with lean controls (36.2 ± 18.2 and 39.1 ± 8.0 vs. −13.7 ± 8.7, P < 0.02), and correlated negatively with ISOGTT (r = −0.39, P < 0.05). Conclusion: ROS generation from MNCs in response to hyperglycemia is increased in PCOS independent of obesity. The resultant oxidative stress may contribute to a proinflammatory state that induces insulin resistance and hyperandrogenism in women with this disorder.

Oxidative stress markers in women with polycystic ovary syndrome without insulin resistance

2018 ◽  
Author(s):  
Reveka Gyftaki ◽  
Sofia Gougoura ◽  
Nikolaos Kalogeris ◽  
Vasiliki Loi ◽  
George Koukoulis ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Oxidative Stress Markers ◽  
Ovary Syndrome ◽  
Stress Markers

scholarly journals Increased oxidative stress is associated with insulin resistance and infertility in polycystic ovary syndrome

2016 ◽  
Vol 87 (11) ◽  
pp. 733-738 ◽  
Author(s):  
Alev Özer ◽  
Murat Bakacak ◽  
Hakan Kıran ◽  
Önder Ercan ◽  
Bülent Köstü ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Ovary Syndrome

scholarly journals A COMPARATIVE STUDY OF INSULIN RESISTANCE IN PATIENTS OF POLYCYSTIC OVARY SYNDROME

2021 ◽  
Vol 71 (5) ◽  
pp. 1746-50
Author(s):  
Amena Arif ◽  
Palvasha Waheed ◽  
Robina Anees ◽  
Amir Rashid ◽  
Saleem Ahmed Khan
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Comparative Study ◽  
Polycystic Ovary ◽  
Serum Insulin ◽  
Insulin Level ◽  
Normal Weight ◽  
Ovary Syndrome ◽  
Cross Sectional ◽  
Control Subjects

Objective: To assess the relationship between obesity and insulin resistance in polycystic ovary syndrome affected women. Study Design: Cross sectional comparative study. Place and Duration of Study: Multidisciplinary Lab-I of Department of Biochemistry, Army Medical College, Rawalpindi, in collaboration with Pakistan Naval Ship Hafeez Hospital, Islamabad from Feb 2018 to Jan 2019. Methodology: One hundred and five selected females (puberty till 25 years of age) were divided into three groups of 35 each. Blood samples were collected an overnight fast (from 8-11 AM). Serum level of insulin was measured and insulin resistance was calculated based on HOMA-IR. Results: HOMA-IR concentrations correlated directly with Basal Metabolic Index, fasting plasma glucose and serum insulin levels. Mean serum insulin level was also elevated in patients with polycystic ovary syndrome (normal weight & overweight) as compared to control subjects (7.4 ± 1.2 mIU/L & 9.1 ± 0.8 mIU/L vs 6.3 ± 1.1 mIU/L; p as 0.003). The insulin resistance was slightly higher in patients with polycystic ovary syndrome as compared to the control subjects (1.4 ± 0.3 & 1.7 ± 0.2 vs. 1.1 ± 0.3; p<0.001). Conclusion: HOMA-IR levels are positively associated with BMI, the intensity of peripheral insulin resistance in polycystic ovary syndrome-affected females, indicating that normal weight, and overweight patients with polycystic ovary syndrome have tendency towards insulin resistance.

Insulin Resistance in Non-Obese Women with Polycystic Ovary Syndrome: Relation to Byproducts of Oxidative Stress

2011 ◽  
Vol 119 (07) ◽  
pp. 451-455 ◽  
Author(s):  
D. Macut ◽  
T. Simic ◽  
A. Lissounov ◽  
M. Pljesa-Ercegovac ◽  
I. Bozic ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Obese Women ◽  
Ovary Syndrome

No changes of peripheral insulin resistance in polycystic ovary syndrome after long-term reduction of endogenous androgens with leuprolide

1995 ◽  
Vol 133 (6) ◽  
pp. 718-722 ◽  
Author(s):  
Antonino Lasco ◽  
Domenico Cucinotta ◽  
Alfonso Gigante ◽  
Giulia Denuzzo ◽  
Marilena Pedulla ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Obese Women ◽  
Ovary Syndrome ◽  
Control Subjects ◽  
Peripheral Insulin Resistance ◽  
Androgen Levels

Lasco A, Cucinotta D, Gigante A, Denuzzo G, Pedulla M, Trifiletti A, Frisina N. No changes of peripheral insulin resistance in polycystic ovary syndrome after long-term reduction of endogenous androgens with leuprolide. Eur J Endocrinol 1995;133:718–22. ISSN 0804–4643 The aim of this study was to investigate the relationship between plasma insulin levels, peripheral insulin sensitivity and androgen secretion in ten patients with polycystic ovary syndrome and in six obese women as compared with six normal-weight control subjects. During a euglycemic–hyperinsulinemic clamp no significant change of testosterone, androstenedione or dehydroepiandrosterone sulfate plasma levels was observed in the two groups of patients or in the control subjects; insulin sensitivity was clearly reduced and was similar in polycystic ovary patients and in obese women, in spite of the different plasma androgen levels. A long-term (5 months) androgen suppression with the gonadotropin-releasing hormone agonist leuprolide was not able to improve significantly the insulin sensitivity. These results demonstrate that the short-term hyperinsulinemia achieved with the clamp technique does not affect androgen secretion and that insulin resistance, measured with the same technique, is not influenced by long-term suppression of plasma androgen levels in polycystic ovary syndrome. A Lasco, Via Faustina e Tertullo 19, 98100 Messina, Italy

scholarly journals Oxidative Stress and Low-Grade Inflammation in Polycystic Ovary Syndrome: Controversies and New Insights

2021 ◽  
Vol 22 (4) ◽  
pp. 1667 ◽  
Author(s):  
Antonio Mancini ◽  
Carmine Bruno ◽  
Edoardo Vergani ◽  
Claudia d’Abate ◽  
Elena Giacchi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Vitamin D ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Normal Weight ◽  
Low Grade ◽  
Ovary Syndrome ◽  
Low Grade Inflammation

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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