González, FrankConsidine, Robert V.Abdelhadi, Ola A.Acton, Anthony J.2022-07-152022-07-152020-06-01González F, Considine RV, Abdelhadi OA, Acton AJ. Inflammation Triggered by Saturated Fat Ingestion Is Linked to Insulin Resistance and Hyperandrogenism in Polycystic Ovary Syndrome. J Clin Endocrinol Metab. 2020;105(6):e2152-e2167. doi:10.1210/clinem/dgaa108https://hdl.handle.net/1805/29596Context: 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.en-USPublisher PolicyHyperandrogenismInsulin resistancePolycystic ovary syndromeSaturated fatArticle