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      Lipidomic analysis of plasma samples from women with polycystic ovary syndrome

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          Abstract

          Polycystic ovary syndrome (PCOS) is a common disorder affecting between 5 and 18 % of females of reproductive age and can be diagnosed based on a combination of clinical, ultrasound and biochemical features, none of which on its own is diagnostic. A lipidomic approach using liquid chromatography coupled with accurate mass high-resolution mass-spectrometry (LC-HRMS) was used to investigate if there were any differences in plasma lipidomic profiles in women with PCOS compared with control women at different stages of menstrual cycle. Plasma samples from 40 women with PCOS and 40 controls aged between 18 and 40 years were analysed in combination with multivariate statistical analyses. Multivariate data analysis (LASSO regression and OPLS-DA) of the sample lipidomics datasets showed a weak prediction model for PCOS versus control samples from the follicular and mid-cycle phases of the menstrual cycle, but a stronger model (specificity 85 % and sensitivity 95 %) for PCOS versus the luteal phase menstrual cycle controls. The PCOS vs luteal phase model showed increased levels of plasma triglycerides and sphingomyelins and decreased levels of lysophosphatidylcholines and phosphatidylethanolamines in PCOS women compared with controls. Lipid biomarkers of PCOS were tentatively identified which may be useful in distinguishing PCOS from controls especially when performed during the menstrual cycle luteal phase.

          Electronic supplementary material

          The online version of this article (doi:10.1007/s11306-014-0726-y) contains supplementary material, which is available to authorized users.

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          Most cited references 23

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          Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome.

            (2003)
          Since the 1990 National Institutes of Health-sponsored conference on polycystic ovary syndrome (PCOS), it has become appreciated that the syndrome encompasses a broader spectrum of signs and symptoms of ovarian dysfunction than those defined by the original diagnostic criteria. The 2003 Rotterdam consensus workshop concluded that PCOS is a syndrome of ovarian dysfunction along with the cardinal features hyperandrogenism and polycystic ovary (PCO) morphology. PCOS remains a syndrome, and as such no single diagnostic criterion (such as hyperandrogenism or PCO) is sufficient for clinical diagnosis. Its clinical manifestations may include menstrual irregularities, signs of androgen excess, and obesity. Insulin resistance and elevated serum LH levels are also common features in PCOS. PCOS is associated with an increased risk of type 2 diabetes and cardiovascular events.
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            Metabonomics reveals plasma metabolic changes and inflammatory marker in polycystic ovary syndrome patients.

            Polycystic ovary syndrome (PCOS) is a common, clinically heterogeneous endocrine disorder affecting women of reproductive age, associated with endocrinopathy and metabolic abnormalities. Although some metabolic parameters have been investigated, very little information has been reported on the changes of small metabolites in biofluids. The aim of this study was to establish the metabolic profile of PCOS and compare it with that of controls. In this cross-sectional study of 34 women with PCOS and 36 controls, contents of small metabolites and lipids in plasma samples were measured using nuclear magnetic resonance (NMR)-based techniques and analyzed using multivariate statistical methods. Significant decrease (P < 0.05) in the levels of amino acids (leucine, isoleucine, methionine, glutamine, and arginine), citrate, choline, and glycerophosphocholine/phosphocholine (GPC/PC), and increase (P < 0.05) in the levels of lactate, dimethylamine (DMA), creatine, and N-acetyl glycoproteins were observed in PCOS patients compared with the controls. Subgroups of patients with obesity, metabolic syndrome, or hyperandrogenism exhibited greater metabolic deviations than their corresponding subgroups without these factors. PCOS patients have perturbations in amino acid metabolism, the tricarboxylic acid (TCA) cycle, and gut microflora, as well as mild disturbances in glucose and lipid metabolism. The elevated level of N-acetyl glycoproteins demonstrates the existence of low-grade chronic inflammation in PCOS patients.
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              Lipidomics is providing new insight into the metabolic syndrome and its sequelae.

              The metabolic syndrome incorporating obesity, hypertension, dyslipidaemia and elevated plasma glucose has reached epidemic proportions in many Western countries leading to a dramatic increase in insulin resistance, steatosis and type 2 diabetes. Lipidomics presents a new set of tools to unravel the relationship between hyper-caloric diets and other environmental and genetic factors with the metabolic syndrome and disease progression. Plasma lipidomic studies are providing detailed characterisation of the dyslipidaemia associated with obesity and the metabolic syndrome. Combined with lipoprotein fractionation and dynamic modelling we are gaining a new comprehension of lipoprotein composition structure and function. At the population level genome-wide association studies are identifying potential loci linking lipid metabolism with disease pathogenesis. Analysis of tissue, cell and even organelle lipidomes are unravelling the complex relationships between lipotoxicity, inflammation, oxidative stress and cellular function. The global view of lipid metabolism offered by lipidomics is accelerating our understanding of disease processes and identifying new avenues of research into metabolic syndrome and its sequelae. The ongoing identification and validation of lipid biomarkers will likely see their introduction into clinical practice for improved quantification of disease risk, earlier identification of disease and improved patient management in the near future.
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                Author and article information

                Contributors
                david.barrett@nottingham.ac.uk
                0115 82 30712 , william.atiomo@nottingham.ac.uk
                Journal
                Metabolomics
                Metabolomics
                Metabolomics
                Springer US (New York )
                1573-3882
                1573-3890
                17 August 2014
                17 August 2014
                2015
                : 11
                : 3
                : 657-666
                Affiliations
                [ ]Centre for Analytical Bioscience, School of Pharmacy, University of Nottingham, Nottingham, UK
                [ ]School of Medicine, Queen’s Medical Centre, University of Nottingham, Nottingham, NG7 2UH UK
                [ ]School of Biosciences, University of Nottingham, Nottingham, LE12 5RD UK
                [ ]MetaboConsult UK, Derby, UK
                Article
                726
                10.1007/s11306-014-0726-y
                4419155
                © The Author(s) 2014

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.

                Categories
                Original Article
                Custom metadata
                © Springer Science+Business Media New York 2015

                Molecular biology

                polycystic ovary syndrome, lipidomics, biomarkers, menstrual cycle

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