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 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 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 stimulates proatherogenic inflammation in polycystic ovary syndrome

2021 ◽  
Author(s):  
Frank Gonzalez ◽  
Robert V Considine ◽  
Ola A. Abdelhadi ◽  
Jiaping Xue ◽  
Anthony J. Acton
Keyword(s):  
Gene Expression ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Saturated Fat ◽  
Oral Glucose ◽  
Abdominal Adiposity ◽  
Hsp 70 ◽  
Ovary Syndrome ◽  
Tlr2 Gene ◽  
Androgen Secretion

Inflammation and dyslipidemia are often present in Polycystic Ovary Syndrome (PCOS). We determined the effect of saturated fat ingestion on circulating heat shock protein-70 (HSP-70) and mononuclear cell (MNC) toll-like receptor-2 (TLR2) gene expression, activator protein-1 (AP-1) activation and matrix matalloproteinase-2 (MMP-2) protein in women with PCOS. Twenty reproductive-age women with PCOS (10 lean, 10 with obesity) and 20 ovulatory controls (10 lean, 10 with obesity) participated in the study. HSP-70 was measured in serum and TLR2 mRNA and protein, AP-1 activation and MMP-2 protein were quantified in MNC from blood drawn 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 fasting and 24, 48 and 72 hours after HCG administration. In response to saturated fat ingestion, serum HSP-70, TLR2 gene expression, activated AP-1 and MMP-2 protein were greater in lean women with PCOS compared with lean controls, and in women with PCOS and obesity compared with controls with obesity. Both PCOS groups exhibited lower ISOGTT and greater HCG-stimulated androgen secretion compared with control subjects. Lipid-stimulated proatherogenic inflammation marker responses were negatively correlated with ISOGTT, and positively correlated with abdominal adiposity and HCG-stimulated androgen secretion. In PCOS, saturated fat ingestion stimulates proatherogenic inflammation independent of obesity. This effect is greater when PCOS is combined with obesity compared with obesity alone. Abdominal adiposity and hyperandrogenism may perpetuate proatherogenic inflammation.

scholarly journals Racial and Ethnic Differences in Metabolic Disease in Adolescents With Obesity and Polycystic Ovary Syndrome

2021 ◽  
Vol 5 (4) ◽  
Author(s):  
Stanley Andrisse ◽  
Yesenia Garcia-Reyes ◽  
Laura Pyle ◽  
Megan M Kelsey ◽  
Kristen J Nadeau ◽  
...  
Keyword(s):  
Metabolic Disease ◽  
Insulin Resistance ◽  
General Population ◽  
Polycystic Ovary Syndrome ◽  
Race And Ethnicity ◽  
Polycystic Ovary ◽  
Sex Hormone Binding Globulin ◽  
Oral Glucose ◽  
Model Assessment ◽  
Ovary Syndrome

Abstract Context Polycystic ovary syndrome (PCOS) is common and associated with metabolic syndrome. In the general population, metabolic disease varies by race and ethnicity. Objective This work aimed to examine in depth the interaction of race and ethnicity with PCOS-related metabolic disease in adolescent youth. Methods A secondary analysis was conducted of data from girls (age 12-21 years) with overweight or obesity (> 90 body mass index [BMI] percentile) and PCOS. Measurements included fasting hormone and metabolic measures, a 2-hour oral glucose tolerance test (OGTT), and magnetic resonance imaging for hepatic fat. Groups were categorized by race or ethnicity. Results Participants included 39 non-Hispanic White (NHW, age 15.7 ± 0.2 years; BMI 97.7 ± 0.2 percentile), 50 Hispanic (HW, 15.2 ± 0.3 years; 97.9 ± 0.3 percentile), and 12 non-Hispanic Black (NHB, 16.0 ± 0.6 years; 98.6 ± 0.4 percentile) adolescents. Hepatic markers of insulin resistance were worse in NHW, including lower sex hormone–binding globulin and higher triglycerides over high-density lipoprotein cholesterol (TGs/HDL-C) ratio (P = .002 overall, HW vs NHB [P = .009] vs NHW [P = 0.020]), although homeostasis model assessment of estimated insulin resistance was worst in NHB (P = .010 overall, NHW vs NHB P = .014). Fasting and 2-hour OGTT glucose were not different between groups, although glycated hemoglobin A1c (HbA1c) was lowest in NHW (overall P < .001, NHW 5.2 ± 0.3 vs HW 5.5 ± 0.3 P < .001 vs 5.7 ± 0.4%, P < .001). The frequency of hepatic steatosis (HW 62%, NHW 42%, NHB 25%, P = .032); low HDL-C < 40 mg/dL (HW 82%, NHW 61%, NHB 50%, P < .001) and prediabetes HbA1c 5.7% to 6.4% (NHB 50%, HW 36%, NHW 5%, P < .001) were different between the groups. Conclusion Adolescents with PCOS appear to show similar racial and ethnic variation to the general population in terms of metabolic disease components.

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.

Bone Mineral Density is Unaltered in Women with Polycystic Ovary Syndrome

2018 ◽  
Vol 50 (10) ◽  
pp. 754-760 ◽  
Author(s):  
Mohd Ganie ◽  
Semanti Chakraborty ◽  
Ashish Sehgal ◽  
M. Sreejith ◽  
Devasenathipathy Kandasamy ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Bone Mineral ◽  
Young Women ◽  
Polycystic Ovary ◽  
Oral Glucose ◽  
Model Assessment ◽  
Mineral Density ◽  
Ovary Syndrome

Abstract Context The effects of endocrine aberrations associated with polycystic ovary syndrome (PCOS) on bone mineral density (BMD) in young women is a matter of debate. Objectives To compare BMD in young women with PCOS to age and body mass index (BMI) matched controls and to elucidate its correlation to BMI, insulin resistance and serum testosterone. Design and Methods We recruited 60 women with PCOS aged 14-24 years, diagnosed based on Rotterdam 2003 criteria, and 58 age matched controls. BMD was measured by dual energy X-ray absorptiometry. In addition, these subjects underwent biochemical and hormonal analysis including oral glucose tolerance test, calculation of Homeostatic Model Assessment–Insulin Resistance Index, measurement of serum thyroxine, thyrotropin, prolactin, total testosterone, dehydroepiandrosterone sulfate, follicular phase luteinizing hormone and follicle stimulating hormone. Results There was no difference of BMD between women with PCOS and control women (1.103±0.08 vs 1.126±0.083 g/cm2; p=0.122). In subgroup analysis based on BMI, BMD in obese women with PCOS was significantly higher than their overweight and lean counterparts at lumbar spine (p<0.001), neck of femur (p=0.005) and total hip (p<0.001). BMD was not different at any site between oligomenorrheic and non-oligomenorrheic women with PCOS. It positively correlated with BMI, waist and hip circumference in women with PCOS. No correlation was found with HOMA-IR or Testosterone. Conclusions BMI is the most important determinant of BMD in women with PCOS. BMD is not different between healthy young women and those with PCOS.

scholarly journals STUDY OF GLYCATED HEMOGLOBIN LEVELS IN POLYCYSTIC OVARY SYNDROME

2018 ◽  
Vol 11 (5) ◽  
pp. 191 ◽  
Author(s):  
Renuka Pangaluri ◽  
Shakthiya T ◽  
Vinodhini Vm
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Glycated Hemoglobin ◽  
Polycystic Ovary ◽  
Resistance Index ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Model Assessment ◽  
Ovary Syndrome ◽  
Hba1c Levels

 Objective: Polycystic ovarian syndrome (PCOS) is often accompanied by insulin resistance, obesity, and cardiometabolic risk factors. Androgen excess-PCOS recommends oral glucose tolerance test or glycated hemoglobin (HbA1C) to evaluate dysglycemia in PCOS subjects. We undertook this study to evaluate the prevalence of elevated HbA1C levels in PCOS women.Methods: The study was carried out among 100 PCOS patients from SRM Hospital, 100 healthy individuals were included as controls. Fasting glucose, HbA1C, Insulin and Homeostasis Model Assessment-Insulin Resistance Index were estimated.Results: Patients with polycystic ovary syndrome showed a significant increase in HbA1C levels (5.799±1.022; 4.96±0.625, p=0.001) when compared to the control group.Conclusion: We found elevated HbA1C levels in PCOS women categorizing 26% as prediabetes and 28% as having type 2 diabetes mellitus.

scholarly journals Insulin sensitizing drugs increase the endogenous dopaminergic tone in obese insulin-resistant women with polycystic ovary syndrome

2005 ◽  
Vol 184 (1) ◽  
pp. 233-239 ◽  
Author(s):  
C Ortega-González ◽  
L Cardoza ◽  
B Coutiño ◽  
R Hidalgo ◽  
G Arteaga-Troncoso ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Polycystic Ovary Syndrome ◽  
Fasting Glucose ◽  
Polycystic Ovary ◽  
Serum Insulin ◽  
Oral Glucose ◽  
Obese Women ◽  
Ovary Syndrome ◽  
Insulin Resistant

To investigate whether the long-term administration of metformin or pioglitazone to women with polycystic ovary syndrome (PCOS) could induce changes in their hypothalamic dopaminergic (DA) tone and to analyze whether these changes correlated with modifications in insulin resistance, we originally studied 57 obese hyperinsulinemic, non-diabetic, insulin resistant women with PCOS, but only 34 completed the study. They were randomly divided into two groups: group one (n=17) received pioglitazone (30 mg/day) and group 2 (n=17) received metformin (850 mg, three times a day) over 24 weeks. All women were identically studied before (basal) and 6 months after (T6) drug administration, including clinical evaluations, a 2 h oral glucose tolerance test (75 g) (OGTT) for glucose and insulin measurements, followed a week later by a 2 h intravenous metoclopramide test (10 mg bolus) for prolactin (PRL) determinations. The areas under the insulin (AUC-insulin) and PRL (AUC-PRL) curves were calculated, along with the index of insulin resistance (HOMA-IR) and the indexes of insulin sensitivity (QUICKI and fasting glucose–insulin ratio). At baseline, women in both groups were of similar age, body weight, body mass index (BMI) and Ferriman-Gallwey hirsutism score (F-G score). At completion of the study, body weight and BMI remained unchanged but the F-G score significantly decreased. Fasting serum insulin concentrations and the AUC-insulin significantly decreased by the end of the trial in a similar fashion in both groups, while the AUC-PRL significantly increased at the end of the trial in both groups. At no time were significant correlations between AUC-PRL and AUC-insulin or the indexes HOMA-IR, QUICKI or fasting glucose–insulin ratio observed. The present results suggests that either pioglitazone or metformin administration was associated with a clear improvement in the endogenous hypothalamic DA tone, simultaneously with an amelioration of the insulin resistance status in these obese women with PCOS.

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

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