Lipidomics reveals altered biosynthetic pathways of glycerophospholipids and cell signaling as biomarkers of the polycystic ovary syndrome

// Mariona Jove 1, * , Irene Pradas 1, * , Alba Naudi 1, * , Susana Rovira-Llopis 2 , Celia Banuls 2 , Milagros Rocha 2 , Manuel Portero-Otin 1 , Antonio Hernandez-Mijares 2, 3, 4, # , Victor M. Victor 2, 5, # and Reinald Pamplona 1, # 1 Department of Experimental Medicine, Lleida University-Institute for Research in Biomedicine of Lleida (UdL-IRBLleida), 25198 Lleida, Spain 2 Foundation for the Promotion of Healthcare and Biomedical Research in the Valencian Community (FISABIO), Service of Endocrinology, University Hospital Dr. Peset, 46017 Valencia, Spain 3 Fundacion Investigacion Hospital Clinico Universitario/INCLIVA, Valencia University, 46010 Valencia, Spain 4 Department of Medicine, Valencia University, 46010 Valencia, Spain 5 Department of Physiology, Valencia University, 46010 Valencia, Spain * These authors contributed equally to this work # These authors share co-senior authorship Correspondence to: Victor M. Victor, email: victor.victor@uv.es Reinald Pamplona, email: reinald.pamplona@mex.udl.cat Keywords: cell signaling molecules; glycerophospholipids; free fatty acids; lipidomics; lipid de novo biosynthesis Received: October 03, 2017 Accepted: December 04, 2017 Published: December 17, 2017 ABSTRACT Purpose: In this work, a non-targeted approach was used to unravel changes in the plasma lipidome of PCOS patients. The aim is to offer new insights in PCOS patients strictly selected in order to avoid confounding factors such as dyslipemia, obesity, altered glucose/insulin metabolism, cardiovascular disease, or cancer. Results: Multivariate statistics revealed a specific lipidomic signature for PCOS patients without associated pathologies. This signature implies changes, mainly by down-regulation, in glycerolipid, glycerophospholipid and sphingolipid metabolism suggesting an altered biosynthetic pathway of glycerophospholipids and cell signaling as second messengers in women with PCOS. Conclusions: Our study confirms that a lipidomic approach discriminates a specific phenotype from PCOS women without associated pathologies from healthy controls. Methods: In a cross-sectional pilot study, data were obtained from 34 subjects, allocated to one of two groups: a) lean, healthy controls ( n = 20), b) PCOS patients ( n = 14) with diagnosis based on hyperandrogenaemia, oligo-anovulation and abnormal ovaries with small follicular cysts. A detailed biochemical characterization was made and lipidomic profiling was performed via an untargeted approach using LC-ESI-QTOF MS/MS.