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, p47(Phox) 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 p47(phox) 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 p47(phox) mRNA and protein content as well as plasma TBARS compared with lean control subjects. Both PCOS groups exhibited lower IS(OGTT )and greater HCG-stimulated androgen secretion compared with control subjects. The ROS generation, p47(phox), and TBARS responses were negatively correlated with ISOGTT and positively correlated with HCG-stimulated androgen secretion. Conclusion: In PCOS, increases in ROS generation, p47(phox) 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.