Inflammation triggered by saturated fat ingestion is linked to insulin resistance and hyperandrogenism in polycystic ovary syndrome

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-βB (NFβB) activation; NFβB, inhibitory-βBa (IβBa), and tumor necrosis factor-a(TNFa) 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 20ovulatory controls (10 lean, 10 with obesity).Main Outcome Measures: Activated NFβB, NFβB heterodimer subunits, IβBa and TNFamessenger ribonucleic acid content and NFβB p65 and IβBa protein content were quantified inmononuclear 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 tolerancetesting (ISOGTT). Androgen secretion was assessed from blood drawn fasting and 24, 48, and 72 hafter human chorionic gonadotropin (HCG) administration.Results: In response to saturated fat ingestion, women with PCOS regardless of weight classexhibited lipid-induced increases in activated NFβB, NFβB, and TNFa gene expression and plasmaCRP and decreases in IβBa protein compared with lean control subjects. Both PCOS groupsexhibited lower ISOGTT and greater HCG-stimulated androgen secretion compared with controlsubjects. Lipid-stimulated NFβB activation was negatively correlated with ISOGTT, and positivelycorrelated with HCG-stimulated androgen secretion.Conclusion: In PCOS, increases in NFβB activation and circulating CRP and decreases in IβBaprotein following saturated fat ingestion are independent of obesity. Circulating MNC andexcess adipose tissue are separate and distinct contributors to inflammation in this disorder.