Abnormal expression of genes involved in inflammation, lipid metabolism, and Wnt signaling in the adipose tissue of polycystic ovary syndrome

Context: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women. Objective: Our objective was to compare gene expression pattern in sc abdominal adipose tissue in nonobese PCOS patients vs. body mass index-matched controls. Research Design and Methods: Eleven PCOS subjects and 12 controls (body mass index 20-28 kg/m²) were recruited. Total RNA was isolated, and gene expression profiling was performed using Affymetrix Human Genome U133 arrays. Differentially expressed genes were classified by gene ontology. Microarray results for selected genes were confirmed by quantitative real-time PCR (RT-qPCR). Frequently sampled iv glucose tolerance tests were used to assess dynamic insulin sensitivity. Results: Ninety-six genes were identified with altered expression of at least 2-fold in nonobese PCOS adipose tissues. Inflammatory response genes were significantly down-regulated. RT-qPCR confirmed decreases in expression of IL6 (12.3-fold), CXCL2(18.3-fold), and SOCS3(22.6-fold). Lipid metabolism genes associated with insulin resistance were significantly up-regulated, with confirmed increases in DHRS9 (2.5-fold), UCLH1 (2.6-fold), and FADS1 (2.8-fold) expression. Wnt signaling genes (DKK2, JUN, and FOSB) were differentially expressed. RT-qPCR confirmed significant expression changes in DKK2 (1.9-fold increase), JUN (4.1-fold decrease), and FOSB (60-fold decrease). Conclusions: Genes involved in inflammation, lipid metabolism, and Wnt signaling are differentially expressed in nonobese PCOS adipose tissue. Because these genes are known to affect adipogenesis and insulin resistance, we hypothesize that their dysregulation may contribute to the metabolic abnormalities observed in women with PCOS.