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 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 Lipid-induced mononuclear cell cytokine secretion in the development of metabolic aberration and androgen excess in polycystic ovary syndrome

2020 ◽  
Vol 35 (5) ◽  
pp. 1168-1177
Author(s):  
F González ◽  
R V Considine ◽  
O A Abdelhadi ◽  
A J Acton
Keyword(s):  
Insulin Sensitivity ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Saturated Fat ◽  
National Institutes Of Health ◽  
Reproductive Age ◽  
Androgen Excess ◽  
Ovary Syndrome ◽  
Reproductive Age Women ◽  
Androgen Secretion

Abstract STUDY QUESTION What is the effect of saturated fat ingestion on mononuclear cell (MNC) TNFα, IL-6 and IL-1β secretion and circulating IL-6 levels in women with polycystic ovary syndrome (PCOS)? SUMMARY ANSWER Women with PCOS exhibit increases in MNC-derived TNFα, IL-6 and IL-1β secretion and circulating IL-6 following saturated fat ingestion even in the absence of obesity, and these increases are linked to metabolic aberration and androgen excess. WHAT IS KNOWN ALREADY Cytokine excess and metabolic aberration is often present in PCOS. STUDY DESIGN, SIZE, DURATION A cross-sectional design was used in this study of 38 reproductive-age women. PARTICIPANTS/MATERIALS, SETTING, METHODS Groups of 19 reproductive-age women with PCOS (10 lean, 9 obese) and 19 ovulatory controls (10 lean, 9 obese) participated in this study that was performed at a tertiary academic medical centre. TNFα, IL-6 and IL-1β secretion was measured from cultured MNC, and IL-6 was measured in plasma from blood sampling while fasting and 2, 3 and 5 h after saturated fat ingestion. Insulin sensitivity was determined using the Matsuda index following an oral glucose tolerance test. Androgen secretion was evaluated with blood sampling while fasting and 24, 48 and 72 h after an HCG injection. MAIN RESULTS AND THE ROLE OF CHANCE Lean and obese women with PCOS exhibited lipid-induced incremental AUC increases in MNC-derived TNFα (489–611%), IL-6 (333–398%) and IL-1β (560–695%) secretion and in plasma IL-6 levels (426–474%), in contrast with lean control subjects. In both PCOS groups, insulin sensitivity was lower (42–49%) and androgen secretion after HCG injection was greater (63–110%) compared with control subjects. The MNC-derived TNFα, IL-6 and IL-1β and circulating IL-6 responses were inversely associated with insulin sensitivity and directly associated with fasting lipids and androgen secretion after HCG injection. LIMITATIONS, REASONS FOR CAUTION The sample size of each of the four study groups was modest following group assignment of subjects by body mass. WIDER IMPLICATIONS OF THE FINDINGS This study showcases the unique pro-inflammatory contribution of circulating MNC in the development of metabolic aberration and androgen excess in PCOS. STUDY FUNDING/COMPETING INTEREST(S) This research was supported by grant R01 DK107605 to F.G. from the National Institutes of Health, the Indiana Clinical and Translational Sciences Institute Clinical Research Center which is funded in part by grant UL1TR002529 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award, and the Indiana University Center for Diabetes and Metabolic Diseases funded by grant P30 DK097512 from the National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. No conflicts of interest, financial or otherwise, are declared by the authors. TRIAL REGISTRATION NUMBER ClinicalTrials.gov NCT01489319

The effects of fish oil on gene expression in patients with polycystic ovary syndrome

2018 ◽  
Vol 48 (3) ◽  
pp. e12893 ◽  
Author(s):  
Elham Rahmani ◽  
Mehri Jamilian ◽  
Bahareh Dadpour ◽  
Zahra Nezami ◽  
Zahra Vahedpoor ◽  
...  
Keyword(s):  
Gene Expression ◽  
Polycystic Ovary Syndrome ◽  
Fish Oil ◽  
Polycystic Ovary ◽  
Ovary Syndrome
Sign in / Sign up

Export Citation Format

Share Document