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

Abstract

Common pathophysiologic characteristics associated with polycystic ovary syndrome (PCOS) include insulin resistance (IR) and hyperinsulinemia. Previous studies have suggested that decreased secretion of high-molecular-weight (HMW) adiponectin from adipocytes contributes to both obesity (elevated body mass index [BMI]) and IR in patients with PCOS. Some investigators have hypothesized that additional variables other than IR and BMI may be involved in the regulation of HMW adiponectin in PCOS. This cross-sectional study investigated potential variables in plasma and adipose tissue that may regulate HMW adiponectin in a cohort of women with PCOS. The study subjects were a well-characterized cohort with PCOS (n = 98) and BMI-matched controls (n = 103). A second cohort included a subset of 136 patients (68 age-, BMI-, and IR-matched pairs of PCOS women and controls). Each participant was given a 75-g oral glucose tolerance test. Gene expression in adipose tissue was examined using biopsied tissue samples from a subset of women with (n = 8) and without PCOS (n = 9). The primary study outcome measures included the relationship between serum levels of HMW adiponectin and variables associated with PCOS for the following: (1) indices of insulin sensitivity, body composition, and plasma androgens and (2) adipose tissue levels of the adiponectin gene (ADIPOQ), peroxisome proliferator-activated receptor γ, tumor necrosis factor α, and androgen receptor(AR). Multiple linear regression analysis was conducted to assess the relationship between HMW adiponectin and variables associated with PCOS. Plasma levels of HMW adiponectin were significantly lower in women with PCOS compared with both BMI-matched controls (P = 0.02) and BMI- and IR-matched controls (P = 0.027). Although BMI and IR were the primary independent predictors of HMW adiponectin, other variables were also involved. A significant interaction occurred between plasma testosterone and waist-to-hip ratio that had a combined influence on plasma levels of HMW adiponectin (P = 0.026). Gene expression analysis in adipose tissue showed that ADIPOQ mRNA levels were not increased in PCOS compared with controls; however, levels of tumor necrosis factor α and androgen receptor mRNA were significantly upregulated (P = 0.003) and P = 0.008, respectively). These findings confirm previous studies showing that plasma HMW adiponectin is reduced in PCOS women compared with controls, independent of BMI and IR. Combined effects of waist-to-hip ratio and plasma testosterone may also regulate HMW adiponectin. In addition, the data suggest that several key genes in adipose tissue may also contribute to reduced HMW adiponectin in PCOS.