Oncotarget

Research Papers:

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

Mariona Jové, Irene Pradas, Alba Naudí, Susana Rovira-Llopis, Celia Bañuls, Milagros Rocha, Manuel Portero-Otin, Antonio Hernández-Mijares, Victor M. Victor _ and Reinald Pamplona

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Oncotarget. 2018; 9:4522-4536. https://doi.org/10.18632/oncotarget.23393

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Abstract

Mariona Jové1,*, Irene Pradas1,*, Alba Naudí1,*, Susana Rovira-Llopis2, Celia Bañuls2, Milagros Rocha2, Manuel Portero-Otin1, Antonio Hernández-Mijares2,3,4,#, Victor M. Victor2,5,# and Reinald Pamplona1,#

1Department of Experimental Medicine, Lleida University-Institute for Research in Biomedicine of Lleida (UdL-IRBLleida), 25198 Lleida, Spain

2Foundation for the Promotion of Healthcare and Biomedical Research in the Valencian Community (FISABIO), Service of Endocrinology, University Hospital Dr. Peset, 46017 Valencia, Spain

3Fundación Investigación Hospital Clínico Universitario/INCLIVA, Valencia University, 46010 Valencia, Spain

4Department of Medicine, Valencia University, 46010 Valencia, Spain

5Department 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.


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