Saturated fat ingestion stimulates proatherogenic inflammation in polycystic ovary syndrome

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.

THE NATURE OF REPRODUCTIVE DISORDERS IN WOMEN WITH HYPERANDROGENISM SYNDROMEq

PCOS occupies a leading place in the population of women with clinical manifestations of excessive androgen secretion and is detected in 72.1-82% of cases, while among women with anovulatory infertility-in 55-91% of cases (Lizneva D. (2016). The criteria, prevalence and phenotypes of PCOS. Fertil.Steril., 106 (1), 6-15). The article discusses the results of a study conducted based on the City Perinatal Center of Tashkent to study the frequency and nature of reproductive disorders in women with symptoms of hyperandrogenism. The study involved women of reproductive age with various menstrual disorders and infertility. The analysis of anamnestic, subjective and objective, clinical and laboratory data of patients was carried out

Salicylate administration suppresses the inflammatory response to nutrients and improves ovarian function in polycystic ovary syndrome

Oxidative stress (OS) and inflammation are often present in polycystic ovary syndrome (PCOS). We examined the effects of salsalate treatment on nutrient-induced OS and inflammation, ovarian androgen secretion, ovulation, and insulin sensitivity in PCOS. Eight lean insulin-sensitive women with PCOS and eight age- and body composition-matched ovulatory controls for baseline comparison participated in the study. The women with PCOS underwent a 12-wk treatment of salsalate, a nonsteroidal anti-inflammatory drug, at a dose of 3 g daily. Markers of OS and inflammation were quantified in mononuclear cells (MNC) and plasma from blood drawn fasting and 2 h after saturated fat ingestion before and after treatment. Ovarian androgen secretion was assessed from blood drawn fasting and 24, 48, and 72 h after human chorionic gonadotropin (HCG) administration before and after treatment. Ovulation was documented based on biphasic basal body temperatures and luteal range progesterone elevations. A two-step pancreatic clamp was performed pre- and posttreatment to measure basal endogenous glucose production (EGP) and the steady-state glucose disposal rate (GDR) during the euglycemic phase and markers of OS and inflammation in MNC and plasma during the hyperglycemic phase. Salsalate administration suppressed lipid- and glucose-stimulated reactive oxygen species generation, activated nuclear factor-κB and circulating tumor necrosis factor-α, normalized basal androgen levels, and lowered HCG-stimulated androgen secretion without altering EGP or GDR. Four salsalate-treated subjects responded with two consecutive ovulations. We conclude that in PCOS, salsalate-induced suppression of OS and inflammation ameliorates ovarian androgen hypersecretion and may induce ovulation while maintaining insulin action.

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

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

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

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.

Androgen secretion in women with threatened miscarriage

Objective. To assess androgen secretion and its possible effect on pregnancy in women with threatened miscarriage in the first trimester. Patients and methods. This prospective observational study included 120 pregnant women divided into four groups. Group I comprised 32 patients with threatened miscarriage and hyperandrogenism who received corticosteroids; Group II was composed of 28 patients with threatened miscarriage and hyperandrogenism who did not receive corticosteroids; Group III included 30 patients with threatened miscarriage and no hyperandrogenism; and Group IV comprised 30 women with normal pregnancy. Serum levels of dehydroepiandrosterone sulfate (DHEA-S), 17-hydroxyprogesterone (17-OHP), and total testosterone were measured on the following weeks of gestation: 5–8, 9–12, 13–18, 19–24, and 25–32. We also evaluated clinical outcomes of pregnancy. Results. We observed no significant differences in 17-ОНР and DHEA-S secretion between women from Group III and controls. Patients from Group II demonstrated higher hormone levels than controls; however, their dynamics of 17-ОНР and testosterone secretion was similar to that in women without hyperandrogenism, so their DHEA-S levels decreased and reached control values by the third trimester. Corticosteroids reduced 17-ONR secretion in the second and third trimesters and DHEA-S secretion in the third trimester. Women receiving corticosteroids demonstrated the poorest clinical pregnancy outcomes. Conclusion. Hyperandrogenism should be considered as one of the risk factors for poor pregnancy outcomes. Administration of corticosteroids to reduce androgen levels impairs normal dynamics of their secretion, does not improve pregnancy outcomes, and is potentially harmful; therefore, these drugs should not be used for such purposes. Key words: pregnancy, hyperandrogenism, corticosteroid therapy, pregnancy outcomes, pregnancy loss, androgen secretion, threatened miscarriage

The Obsidian Impediment - Comedones

Comedones appear as blackheads and whiteheads and implicate cutaneous zones with dense sebaceous follicles, particularly the face, upper chest or dorsal torso. Acne vulgaris is frequently enunciated with comedones. Hyper-proliferation and aberrant desquamation of ductal keratinocytes is enunciated which impedes sebum exudation within a pilo-sebaceous duct, thus engendering comedones. Also, a prototypicpilo-sebaceous duct unit metamorphoses into a comedone when progenitor component of the sebaceous glands differentiate into epithelial-like cells.“Micro-comedone theory” cogitates acne configuration as “comedogenesis” which is contingent to androgen secretion, hyper-proliferating keratinocytes with accumulation of keratin and sebum within the pilo-sebaceous unit. Hyperkeratinisation is also due to secretion of pro-inflammatory cytokines interleukin -1 alpha (IL-1α) produced as a result of cutaneous colonization of Propionibacterium acnes.

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

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.