Saturated Fat Ingestion Promotes Lipopolysaccharide-Mediated Inflammation and Insulin Resistance in Polycystic Ovary Syndrome

Abstract

Context Inflammation and insulin resistance (IR) are often present in polycystic ovary syndrome (PCOS). Objective We determined the effect of saturated fat ingestion on circulating lipopolysaccharide (LPS) and mononuclear cell (MNC) toll-like receptor-4 (TLR-4) and suppressor of cytokine signaling-3 (SOCS-3) in women with PCOS. Design Cross-sectional study. Setting Academic medical center. Patients Nineteen reproductive-Age women with PCOS (10 lean, 9 obese) and 19 ovulatory control subjects (10 lean, 9 obese). Main Outcome Measures LPS and TNFα levels were measured in plasma. TLR-4 and SOCS-3 mRNA and protein content were quantified in MNC from blood collected after fasting and 2, 3, and 5 hours after saturated fat ingestion. Insulin sensitivity was derived from an oral glucose tolerance test (IS OGTT). Androgen secretion was assessed from blood collected after fasting and 24, 48, and 72 hours after human chorionic gonadotropin (HCG) administration. Results Regardless of PCOS status, subjects who were obese had lipid-induced increases in circulating LPS and TLR-4 protein content compared with subjects who were lean. Lean and obese women with PCOS had lipid-induced increases in plasma TNFα and SOCS-3 mRNA and protein content compared with lean control subjects. Both PCOS groups had lower IS OGTT and greater HCG-stimulated androgen secretion compared with control subjects. The LPS and SOCS-3 responses were negatively correlated with IS OGTT and positively correlated with HCG-stimulated androgen secretion. Conclusion In PCOS, lipid-induced LPS-mediated inflammation through TLR-4 is associated with obesity and worsened by PCOS, whereas lipid-induced increases in SOCS-3 may represent an obesity-independent, TNFα-mediated mechanism of IR.