High-Molecular-Weight Adiponectin Is Selectively Reduced in Women with Polycystic Ovary Syndrome Independent of Body Mass Index and Severity of Insulin Resistance

• Published in: The journal of clinical endocrinology and metabolism Vol. 95; no. 3; pp. 1378 - 1385
• Main Authors: O'Connor, A, Phelan, N, Tun, T. Kyaw, Boran, G, Gibney, J, Roche, H. M
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01.03.2010; Copyright by The Endocrine Society
• Subjects: Adiponectin - blood; Adult; Anthropometry; Biological and medical sciences; Blood Glucose - metabolism; Body Composition - physiology; Body Mass Index; Cross-Sectional Studies; Endocrinopathies; Enzyme-Linked Immunosorbent Assay; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Glucose Tolerance Test; Humans; Insulin Resistance - physiology; Leptin - blood; Medical sciences; Polycystic Ovary Syndrome - blood; Resistin - blood; Reverse Transcriptase Polymerase Chain Reaction; Severity of Illness Index; Sex Hormone-Binding Globulin - metabolism; Statistics, Nonparametric; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology; Endocrinopathy; Pancreatic hormone; Polycystic ovary; Adiponectin; Body mass index; Reduction; Cyst; Adult; Female; Benign neoplasm; Woman; Nutritional status; Human; Obesity; Nutrition; Nutrition disorder; Female sterility; Metabolic diseases; Severity; Insulin; Female genital diseases; Ovarian diseases; Target tissue resistance; High molecular weight; Insulin resistance; Endocrinology
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2009-1557

Context: High-molecular-weight (HMW) adiponectin contributes to insulin resistance (IR), which is closely associated with the pathophysiology of polycystic ovary syndrome (PCOS). Abnormalities in adipocyte function have been identified in PCOS and potentially contribute to lower adiponectin concentrations. Objective: Our objective was to determine which variables in plasma and adipose tissue influence HMW adiponectin in a well characterized cohort of women with PCOS. Design: This was a cross-sectional study. Settings and Participants: A teaching hospital. Women with PCOS (n = 98) and body mass index (BMI)-matched controls (n = 103) (including 68 age-, BMI-, and IR-matched pairs). Interventions: A standard 75-g oral glucose tolerance test was performed for each participant. Subcutaneous adipose tissue samples were taken by needle biopsy for a subset of PCOS women (n = 9) and controls (n = 8). Main Outcome Measures: Serum levels of HMW adiponectin and their relation to indices of insulin sensitivity, body composition, and circulating androgens as well as adipose tissue expression levels of ADIPOQ, TNFα, PPARγ, and AR were assessed. Results: HMW adiponectin was significantly lower in women with PCOS compared with both BMI- and BMI- and IR-matched controls (P = 0.009 and P = 0.027, respectively). Although BMI and IR were the main predictors of HMW adiponectin, an interaction between waist to hip ratio and plasma testosterone contributed to its variance (P = 0.026). Adipose tissue gene expression analysis demonstrated that AR and TNFα (P = 0.008 and P = 0.035, respectively) but not ADIPOQ mRNA levels were increased in PCOS compared with controls. Conclusions: HMW adiponectin is selectively reduced in women with PCOS, independent of BMI and IR. Gene expression analysis suggests that posttranscriptional/translational modification contributes to reduced HMW adiponectin in PCOS. High molecular weight-adiponectin is selectively reduced in PCOS independent of body mass index and severity of insulin resistance; these reduced concentrations are significantly associated with central adiposity and androgenic status.