Alterations of Sphingolipid Metabolism in Different Types of Polycystic Ovary Syndrome

Juan Li,Jin-Long Song,Hong-Xia Ma,Wan-Ting Wu,Jing-Rong Wang,Zhi-Hong Jiang,Chun-Ren Zhang,Lee-Fong Yau,Jia-Ning Mi,Li-Min Xie,Mao-Hua Lai

doi:10.1038/s41598-019-38944-6

Abstract

The roles of sphingolipids in polycystic ovary syndrome (PCOS) are still unknown. This study aimed to investigate the sphingolipid characteristics for different types of PCOS using liquid chromatography-mass spectrometry (LC-MS). A total of 107 women with PCOS and 37 healthy women as normal controls were studied. PCOS patients were further classified into non-obesity with insulin resistance (IR) (NOIR), obesity with IR (OIR), and non-obesity and non-IR (NIR) subgroups. A total of 87 serum sphingolipids, including 9 sphingosines, 3 sphinganines, 1 sphingosine-1-phosphate (S1P), 19 ceramides (Cers), 1 ceramide-1-phosphate, 44 sphingomyelins (SMs), 4 hexosylceramides, and 6 lactosylceramides (LacCers) were analyzed using an improved sphingolipidomic approach based on LC-MS. Notable elevations in the levels of S1P, Cer, and SM were observed in PCOS patients when compared with healthy women, and SM species with long saturated acyl chains showed potential as novel biomarkers of PCOS. In addition, the level of LacCer was only elevated in NIR, and there was almost no change in NOIR and OIR. This study is the first to report the comprehensive sphingolipidomic profiling of different subgroups of PCOS with or without IR or obesity and suggests that serum sphingolipids might be useful as diagnostic biomarkers for different types of PCOS.

Highlights

The etiology of polycystic ovary syndrome (PCOS) remains unclear[9]
We explored the potential of sphingolipids as biomarkers for PCOS using an integrated sphingolipid analytical platform that combined the advantages of ultra-high performance liquid chromatography (UHPLC)-quadrupole time-of-flight mass spectrometry and UHPLC coupled with triple quadrupole mass spectrometry (UHPLC-QQQ-MS) to qualitatively and quantitatively analyze the sphingolipids in serum samples from healthy women and from different subgroups of PCOS patients
(31.8%) of the 107 PCOS patients presented with a body mass index (BMI) < 25 kg/m2 and homeostatic model assessment of insulin resistance (HOMA-IR) ≥ 2.14 (the non-obesity with IR (NOIR) group), 41 patients (38.3%) had BMI ≥ 25 kg/m2 and HOMA-IR ≥ 2.14 kg/m2 (the obesity with IR (OIR) group), and 32 patients (29.9%) had BMI < 25 kg/m2 and HOMA-IR < 2.14 kg/m2 (the non-obesity and non-IR (NIR) group)

Summary

Introduction

The etiology of PCOS remains unclear[9]. Pathophysiological changes include hypothalamus-pituitary-ovarian axis dysfunction, hyperandrogenism, hyperinsulinemia, insulin resistance (IR), endocrine dysfunction, adrenal dysfunction, etc.[10,11,12]. A lipidomic analysis of serum/plasma samples from PCOS patients was recently performed, and disturbances in fatty acid, glycerolipid, and glycerophospholipid metabolism were shown to be related to the www.nature.com/scientificreports/. We explored the potential of sphingolipids as biomarkers for PCOS using an integrated sphingolipid analytical platform that combined the advantages of ultra-high performance liquid chromatography (UHPLC)-quadrupole time-of-flight mass spectrometry and UHPLC coupled with triple quadrupole mass spectrometry (UHPLC-QQQ-MS) to qualitatively and quantitatively analyze the sphingolipids in serum samples from healthy women and from different subgroups of PCOS patients

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Discussion

Conclusion