linoleic-acid and Polycystic-Ovary-Syndrome

Polycystic ovary syndrome (PCOS) is a variable disorder characterized by a broad spectrum of anomalies, including hyperandrogenemia, insulin resistance, dyslipidemia, body adiposity, low-grade inflammation and increased cardiovascular disease risks. Recently, a new polytherapy consisting of low-dose flutamide, metformin and pioglitazone in combination with an estro-progestagen resulted in the regulation of endocrine clinical markers in young and non-obese PCOS women. However, the metabolic processes involved in this phenotypic amelioration remain unidentified. In this work, we used NMR and MS-based untargeted metabolomics to study serum samples of young non-obese PCOS women prior to and at the end of a 30 months polytherapy receiving low-dose flutamide, metformin and pioglitazone in combination with an estro-progestagen. Our results reveal that the treatment decreased the levels of oxidized LDL particles in serum, as well as downstream metabolic oxidation products of LDL particles such as 9- and 13-HODE, azelaic acid and glutaric acid. In contrast, the radiuses of small dense LDL and large HDL particles were substantially increased after the treatment. Clinical and endocrine-metabolic markers were also monitored, showing that the level of HDL cholesterol was increased after the treatment, whereas the level of androgens and the carotid intima-media thickness were reduced. Significantly, the abundance of azelaic acid and the carotid intima-media thickness resulted in a high degree of correlation. Altogether, our results reveal that this new polytherapy markedly reverts the oxidant status of untreated PCOS women, and potentially improves the pro-atherosclerosis condition in these patients.

Topics: Abdominal Fat; Biomarkers; Carotid Intima-Media Thickness; Chromatography, Gas; Chromatography, Liquid; Dicarboxylic Acids; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Flutamide; Health; Humans; Linoleic Acid; Lipoproteins; Magnetic Resonance Spectroscopy; Metabolomics; Metformin; Multivariate Analysis; Oxidation-Reduction; Pioglitazone; Polycystic Ovary Syndrome; Spectrometry, Mass, Electrospray Ionization; Thiazolidinediones; Young Adult

Polycystic ovary syndrome (PCOS) is a complex syndrome showing clinical features of an endocrine/metabolic disorder, including hyperinsulinemia and hyperandrogenism. Polyunsaturated fatty acids (PUFAs) and their derivatives, both tightly linked to PCOS and obesity, play important roles in inflammation and reproduction.. This study aimed to investigate serum lipid profiles in newly diagnosed patients with PCOS using lipidomics and correlate these features with the hyperinsulinemia and hyperandrogenism associated with PCOS and obesity.. Thirty-two newly diagnosed women with PCOS and 34 controls were divided into obese and lean subgroups. A PCOS rat model was used to validate results of the human studies.. Serum lipid profiles, including phospholipids, free fatty acids (FFAs), and bioactive lipids, were analyzed using gas chromatography-mass spectrometry (MS) and liquid chromatography-MS.. Elevation in phosphatidylcholine and a concomitant decrease in lysophospholipid were found in obese patients with PCOS vs lean controls. Obese patients with PCOS had decreased PUFA levels and increased levels of long-chain saturated fatty acids vs lean controls. Serum bioactive lipids downstream of arachidonic acid were increased in obese controls, but reduced in both obese and lean patients with PCOS vs their respective controls.. Patients with PCOS showed abnormal levels of phosphatidylcholine, FFAs, and PUFA metabolites. Circulating insulin and androgens may have opposing effects on lipid profiles in patients with PCOS, particularly on the bioactive lipid metabolites derived from PUFAs. These clinical observations warrant further studies of the molecular mechanisms and clinical implications of PCOS and obesity.

Topics: Adult; Androgens; Animals; Arachidonic Acid; Blood Glucose; Case-Control Studies; Ceramides; Cholesterol, HDL; Cholesterol, LDL; Chromatography, Liquid; Dehydroepiandrosterone Sulfate; Diet, High-Fat; Disease Models, Animal; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fatty Acids; Fatty Acids, Unsaturated; Female; Gas Chromatography-Mass Spectrometry; Humans; Hyperandrogenism; Hyperinsulinism; Insulin; Linoleic Acid; Lipid Metabolism; Mass Spectrometry; Obesity; Phosphatidic Acids; Phosphatidylglycerols; Polycystic Ovary Syndrome; Rats; Rats, Sprague-Dawley; Sex Hormone-Binding Globulin; Testosterone; Triglycerides; Young Adult