Serum metabolomics study of polycystic ovary syndrome based on UPLC-QTOF-MS coupled with a pattern recognition approach

Abstract

Metabolomics has become an important tool in distinguishing changes in metabolic pathways and the diagnosis of human disease. Polycystic ovary syndrome (PCOS) is a relatively complicated, heterogeneous endocrine disorder. The etiology and pathogenesis of PCOS remain uncertain. In this study, based on the platform of ultra performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) and the method of pattern recognition, a comprehensive metabolomics approach has been applied to explore the changes in metabolic profiling between PCOS patients (n = 20) and controls (n = 15) as well as insulin-resistance (IR) PCOS patients (n = 11) and non-IR PCOS subjects (n = 9) in serum. In total, 36 metabolites were found significantly different between PCOS and controls, and 9 metabolites were discovered significantly different between IR and non-IR PCOS patients. Significant increases in the levels of saturated and unsaturated fatty acids (myristic acid, linoleic acid, 9-/13-HODE, etc.), fatty amides (palmitic amide, oleamide), dehydroepiandrosterone sulfate, L-glutamic acid, azelaic acid, L-glyceric acid, pyroglutamic acid, and decreases in the levels of lysophosphatidylethanolamine, lysophosphatidylcholine, uridine, and L-carnitine were found in PCOS patients compared with controls. In IR PCOS patients, linoleic acid, myristic acid, palmitoleic acid, and vaccenic acid also increased significantly compared with non-IR PCOS patients. All these changed metabolites showed abnormalities of steroid hormone biosynthesis, amino acids and nucleosides metabolism, glutathione metabolism, and lipids and carbohydrates metabolism in PCOS patients. The subgroup IR PCOS patients exhibited greater metabolic deviations than non-IR PCOS patients. These findings may help yield promising insights into the pathogenesis and advance the diagnosis and prevention of PCOS. Graphical Abstract Serum metabolomics signature of polycystic ovary syndrome.

Combining a nontargeted and targeted metabolomics approach to identify metabolic pathways significantly altered in polycystic ovary syndrome

“…The 25(OH)D 2 concentrations measured in PCOS and MetS were indicative of vitamin D deficiency (<20 ng/mL), as defined by the Institute of Medicine (47) and seen in other studies of PCOS (21, 48, 49). Vitamin D deficiency has also been associated with metabolic disturbances such as obesity, insulin resistance, and dyslipidemia (50, 51).…”

“…Escobar-Morreale et al (15) demonstrated that obese women with PCOS had a different profile of fatty acid metabolites suggestive of increased lipolysis compared with nonobese women with PCOS who demonstrated suppression of lipolysis. When comparing obese women with PCOS to nonobese women with PCOS or to BMI-matched controls without PCOS, long-chain fatty acids such as linoleic acid were elevated only in the obese women with PCOS (15); this finding was corroborated by other groups that did not match control groups by BMI (19, 21). The lack of significant differences in the lipid metabolite profile in the current study may be attributable to matching our control group for both obesity and MetS.…”

“…Comparisons to previous studies of plasma metabolomics profiles in PCOS are limited by small sample sizes, further diluted by subgroups of BMI and insulin resistance status (14, 15, 21), as well as by different analytic techniques, including less-sensitive nuclear magnetic resonance or nontargeted metabolomics and lack of BMI matching in control groups (13, 14, 16, 18). Most prior studies used the Rotterdam criteria for PCOS and did not restrict study participants to those with the more severe phenotype of oligomenorrhea and anovulation.…”

“…To date, metabolomic studies in PCOS have evaluated small samples of women or evaluated the effect of multidrug therapy on PCOS (14, 15, 17, 21). In addition, many studies could not examine or control for obesity or differences in insulin sensitivity (12–15, 18, 19).…”

Untargeted metabolomics analysis of adipogenic transformation in OP9‐DL1 cells using liquid chromatography‐mass spectrometry: Implications for thymic adipogenesis

“…Metabolites with a variable importance in the projection (VIP) value >1 by PLS-DA modeling and a P value <0.05 by Student's t-test were considered to be significantly altered (Gao et al, 2013;Dong et al, 2015). The samples were normalized by sum to total peak intensity.…”