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

Abstract

PurposeIn 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.ResultsMultivariate 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.ConclusionsOur study confirms that a lipidomic approach discriminates a specific phenotype from PCOS women without associated pathologies from healthy controls.MethodsIn 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.

Metformin induces lipid changes on sphingolipid species and oxidized lipids in polycystic ovary syndrome women

“…The expanding development of omics approaches has allowed a wider view of the molecular mechanisms underlying human pathology. Indeed, we have recently confirmed a specific plasma lipidomic signature in women with PCOS with respect to healthy individuals 21 . This signature implies changes in the metabolism of glycerolipids, glycerophospholipids and sphingolipids, pointing to changes in the glycerophospholipid biosynthetic pathway and cell signalling.…”

“…In addition to hormonal derangements and altered glucose metabolism, PCOS has traditionally been linked with atherogenic dyslipidemia, a major determinant of cardiovascular diseases 20 . However, a recent study performed with PCOS patients without associated pathologies and presenting a non-pathogenic lipid profile (Total cholesterol, LDL-C, HDL-C and TG) describes the presence of a PCOS lipidomic fingerprint, in which glycerolipid, glycerophospholipid and sphingolipid metabolism is affected 21 , suggesting that these molecules are related to the physiopathology of PCOS and opening up new scenarios in the search for new drugs. Therefore, the lipid profile characterized by high triglycerides 22 , low HDL cholesterol and increased LDL cholesterol, which has been related to androgen excess 22,23 , is a classic profile linked to IR rather than PCOS.…”

“…This signature implies changes in the metabolism of glycerolipids, glycerophospholipids and sphingolipids, pointing to changes in the glycerophospholipid biosynthetic pathway and cell signalling. Besides the documented role of metformin in lipid metabolism, the potential lipidomic changes in response to metformin treatment in PCOS patients has never been addressed and it would be interesting to determine if metformin can restore the previously reported lipidomic profile that is altered during PCOS 21 .…”

Lipid profile of cerebrospinal fluid in multiple sclerosis patients: a potential tool for diagnosis

“…Samples were then shaken vigorously for 2 min. Then methyl tert-butyl ether (MTBE) containing lipid standards 30 (isotopically labelled lipids) was added for external and internal standardization. Samples were then immersed in a water bath (ATU Ultrasonidos, Valencia, Spain) with an ultrasound frequency 40 kHz and power of 100 W, at 10 °C for 30 min.…”

Differences in fatty acid profiles and desaturation indices of abdominal subcutaneous adipose tissue between pregnant women with and without PCOS

“…On the other hand, it has been suggested that FAs are associated with the risk of a wide range of chronic diseases such as PCOS [12,13]. In this regard, trans-FA (TFA) and saturated FA (SFA) are reported to play significant roles in the development of several disorders through their stimulating action and n-3 polyunsaturated fatty acids (PUFA) contribute by their suppressive action [11,[13][14][15]. The increased amounts of linoleic acid (LA; C18:2 n-6) by 136% in the AT over the last half century in the United States [16], and the increase in the dietary n-6:n-3 FA ratio from 1:1 to 20:1 [17], point to their possible roles in chronic diseases such as PCOS.…”