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-kappa B (NF kappa B) activation; NF kappa B, inhibitory-kappa Ba (I kappa B alpha), and tumor necrosis factor-alpha (TNF alpha) 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 NF kappa B, NF kappa B heterodimer subunits, I kappa B alpha and TNF alpha messenger ribonucleic acid content and NF kappa B p65 and I kappa B alpha 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 NF kappa B, NF kappa B, and TNF alpha gene expression and plasma CRP and decreases in I kappa B alpha protein compared with lean control subjects. Both PCOS groups exhibited lower ISOGTT and greater HCG-stimulated androgen secretion compared with control subjects. Lipid-stimulated NF kappa B activation was negatively correlated with ISOGTT, and positively correlated with HCG-stimulated androgen secretion. Conclusion: In PCOS, increases in NF kappa B activation and circulating CRP and decreases in I kappa B alpha 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.