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Differential Gene Expression Profile in Omental Adipose Tissue in Women with Polycystic Ovary Syndrome

Instituto de Investigaciones Biomédicas (M.C., B.P.), Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, E-28029 Madrid, Spain; Department of Endocrinology (J.I.B.-C., G.V., H.F.E.-M.), Hospital Ramón y Cajal and Universidad de Alcalá, and Department of Molecular Genetics (J.L.S.M.), Hospital Universitario Ramón y Cajal, E-28034 Madrid, Spain; and Centro Nacional de Biotecnología (A.B., A.Z.), Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, E-28049 Madrid, Spain

Address all correspondence to: Héctor F. Escobar-Morreale, M.D., Ph.D., Department of Endocrinology, Hospital Ramón y Cajal & University of Alcalá, Carretera de Colmenar km 9'1, E-28034 Madrid, Spain. E-mail: hescobarm.hrc{at}salud.madrid.org. Address all requests for reprints to: Belén Peral, Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas & Universidad Autónoma de Madrid, Arturo Duperier, 4, E-28029 Madrid, Spain. E-mail: bperal{at}iib.uam.es.

Context: The polycystic ovary syndrome (PCOS) is frequently associated with visceral obesity, suggesting that omental adipose tissue might play an important role in the pathogenesis of the syndrome.

Objective: The objective was to study the expression profiles of omental fat biopsy samples obtained from morbidly obese women with or without PCOS at the time of bariatric surgery.

Design: This was a case-control study.

Settings: We conducted the study in an academic hospital.

Patients: Eight PCOS patients and seven nonhyperandrogenic women submitted to bariatric surgery because of morbid obesity.

Interventions: Biopsy samples of omental fat were obtained during bariatric surgery.

Main Outcome Measure: The main outcome measure was high-density oligonucleotide arrays.

Results: After statistical analysis, we identified changes in the expression patterns of 63 genes between PCOS and control samples. Gene classification was assessed through data mining of Gene Ontology annotations and cluster analysis of dysregulated genes between both groups. These methods highlighted abnormal expression of genes encoding certain components of several biological pathways related to insulin signaling and Wnt signaling, oxidative stress, inflammation, immune function, and lipid metabolism, as well as other genes previously related to PCOS or to the metabolic syndrome.

Conclusion: The differences in the gene expression profiles in visceral adipose tissue of PCOS patients compared with nonhyperandrogenic women involve multiple genes related to several biological pathways, suggesting that the involvement of abdominal obesity in the pathogenesis of PCOS is more ample than previously thought and is not restricted to the induction of insulin resistance.

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