http://www.revistadechimie.ro REV.CHIM.(Bucharest)♦70♦ No. 10 ♦2019 3644 Metabolic Analysis in Women with Polycystic Ovary Highlight Specific Biomarkers of Insulin Resistance CAMELIA LARISA VONICA 1 , ADRIANA FODOR 1,3 , GABRIELA ROMAN 1,3 , ANDRADA ALINA MUREASAN 1 , ANCA DANIELA FARCAS 2,4 *,GEORGETA VICTORIA INCEU 1 , ADRIANA RUSU 1 , CARMEN EMANUELA GEORGESCU 1,5 1 Iuliu Hatieganu University of Medicine and Pharmacy, 6 th Department of Medical Specialities, 8 Victor Babes Str., 400012, Cluj Napoca, Romania 2 Iuliu Hatieganu University of Medicine and Pharmacy, 5 th Department of Internal Medicine, 8 Victor Babes Str., 400012, Cluj Napoca, Romania 3 Emergency County Hospital, Diabetes, Nutrition and Metabolic Diseases Clinic, 3-5 Clinicilor Str, 400006, Cluj Napoca, Romania 4 Emergency County Hospital, Cardiology Department, 3-5 Clinicilor Str, 400006, Cluj Napoca, Romania 5 Emergency County Hospital, Endocrinology, 3-5 Clinic, Clinicilor Str, 400006, Cluj Napoca, Romania The aim of the paper is to detect insulin resistance (IR) biomarkers via metabolomics. It is important to understand the PCOS pathophysiology, diagnosis measures and, subsequently, to improve treatment type and time of IR in PCOS. In most cases, almost half of the women with PCOS have IR which is triggered by inflammation, glucotoxicity and lipotoxicity. In this work was conducted a systematic review of all the papers that used metabolomics for detecting IR biomarkers in PCOS women. The exclusion criteria were: reviews, study population with women bellow 18 years of age, studies including animals and articles not in English, remaining 4 records. The results from the literature shown that phosphatidylcholines were decreased in IR PCOS women when compared to controls. Nonetheless, trans-2-hexenoylcoa, linoleic acid, leucine, myristic acid and palmitic acid regarding lipid metabolism and tyrosine, lysine, phenylalanine α-aminoadipic acid regarding amino acid metabolism were also corelated to IR in PCOS women when compared with healthy or IR controls. Lactate was the only increased metabolite related to glucose metabolism in IR PCOS women. Metabolic alteration in PCOS women with IR when are compared with controls and results that those are brought by both PCOS and IR. Lyso-phosphatidylcholine have an important pro-inflammatory and altered insulin signaling effect, both alterations being considered hallmarks of PCOS women. Serine hyperphosphorylation of the receptor accentuates IR by decreasing the signaling of insulin receptor. Moreover, high levels of lactate correlated with IR in PCOS women may indicate high muscle glycolysis, hepatic glucose production and peripheral glucose uptake. IR biomarkers in PCOS women were evidenced by metabolomics technique. Keywords: Polycystic ovary syndrome, insulin resistance, metabolomics, women, plasma, metabolism, biomarkers. Polycystic ovary syndrome (PCOS) is considered a most frequent endocrine pathology, highly heterogeneous, of women at the childbearing age. Last decades have focused on defining clinical and biochemical characteristics of this syndrome, and also pathophysiological mechanisms and possible causes [1-3]. This syndrome is later diagnosed than its debut. Many women refer to an endocrinologist or gynecologist when they trying to conceive and not succeed. In this case, after pharmacological treatment fails, they try invasive procedures and even in vitro fertilization [4, 5]. Nonetheless, important steps were made regarding the impact of metabolic comorbidities in PCOS women. Between those factors, insulin resistance (IR) and obesity have been linked to the pathogenesis of PCOS, and to the susceptibility of developing early impaired glucose tolerance and cardio-vascular diseases [6]. The metabolic incapacity to adapt to energy requirements or substrate streams leads over time, to organ dysfunction and eventually disease [7]. The omic techniques (Figure 1) have identified various pathways and disease biomarkers in chronic metabolic pathologies like type 2 diabetes mellitus (DM2), IR, dyslipidemia and obesity [8-10]. Of these techniques, metabolomics has recently emerged, being used in small groups also in PCOS women. * email: ancafarcas@yahoo.com, Phone: + 40 744780873 The biomarkers associated with chronic metabolic diseases in terms of branched-chain amino acid catabolism (BCAA), lipid and glucose metabolism [11]. The existing metabolomic studies, which are focused on the study of PCOS, all suggest metabolic alterations regarding carbohydrates, proteins and lipids, all of these are tangled to energy metabolic pathways [12]. Thus, not all studies have focused their attention to eliminate the influence of obesity or insulin resistance in their different stages. Given the strong association of IR with chronic anovulation in PCOS and all the metabolic diseases previously mentioned, all of these are not a consistent diagnostic criterion. In most cases IR is associated with PCOS, independently of obesity and age. Nonetheless, IR is yet scarcely investigated in the absence of impaired glucose tolerance, or in the case of lean PCOS pathology [13]. Consequently, IR assessment in lean PCOS pathology could be underestimated due to the absence of obesity. Hence, the detection of plasma biomarkers which influence insulin signaling, is important for clinical diagnosis a better perception of the mechanisms leading to IR and, better IR treatment for women with PCOS. We have focused the study on metabolomic biomarkers that could define a specific metabolic fingerprint to distinguish between PCOS women with and without IR.