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Serum metabolomics reveals metabolic profiling for women with hyperandrogenism and insulin resistance in polycystic ovary syndrome

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Abstract

Introduction

Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder. Hyperandrogenism (HA) and insulin resistance (IR) are two important pathogenic factors.

Objective

We aimed to investigate the inherent disturbed metabolic profiles for women with HA or IR in PCOS as well as discover diagnostic biomarkers.

Methods

A total of 286 subjects were recruited for the study. They constituted the following groups: healthy women (C), those with HA (B1), those with IR but not obese (B2) and obese women with IR (B3) in PCOS. Nine cross-comparisons with PCOS were performed to characterize metabolic disturbances. Serum metabolomic profiles were determined by gas chromatography–mass spectrometry.

Results and conclusion

We found a total of 59 differential metabolites. 28 metabolites for B1 vs C, 32 for B2 vs C and 25 for B3 vs C were discovered. Among them, palmitic acid, cholesterol, myo-inositol, d-allose, 1,5-anhydro-d-sorbitol, 1-monopalmitin, 1-monostearin, glycerol 1-phosphate, malic acid and citric acid, were the common differential metabolites among B1 vs C, B2 vs C and B3 vs C, which related to biosynthesis of unsaturated fatty acids, citrate cycle etc. Besides, 9-biomarker panel can diagnose well between HA and IR in PCOS. They provided areas under the receiver operating characteristic curve of 0.8511 to 1.000 in the discovery phase, and predictive values of 90% to 92% in the validation set. The result indicated that the differential metabolites can reflect the underlying mechanism of PCOS and serve as biomarkers for complementary diagnosis of HA and IR in PCOS.

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Acknowledgements

This work is financially supported by the National Natural Science Foundation of China (Project Reference Nos. 81803694, 81703691) and the Natural Science Foundation of Jiangsu province (No. BK20151006). We thank Dr. Raphael N. Alolga from China Pharmaceutical University for the editorial services rendered.

Author information

Author notes

  1. Zhihao Zhang and Yanli Hong share co-first authorship. Shijia Liu, Xiaowei Nie, and Wei Zhou share co-senior authorship.

Authors and Affiliations

  1. State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 210009, China

    Zhihao Zhang, Minmin Chen, Ninghua Tan & Wei Zhou

  2. Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, Jiangsu, China

    Yanli Hong, Shijia Liu & Xiaowei Nie

  3. School of Traditional Chinese Pharmacy, China Pharmaceutical University, #639 Longmian Avenue, Jiangning District, Nanjing, 211198, China

    Wei Zhou

  4. Department of Reproductive Center, Affiliated Hospital of Nanjing University of Chinese Medicine, #155 Hanzhong Road, Qinhuai District, Nanjing, 210029, China

    Xiaowei Nie

  5. Department of Clinical Pharmacology, Affiliated Hospital of Nanjing University of Chinese Medicine, #155 Hanzhong Road, Qinhuai District, Nanjing, 210029, China

    Shijia Liu

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  1. Zhihao Zhang
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Contributions

WZ and ZZ designed the study, analyzed the data and wrote the draft of the manuscript. NT designed the study. SL acquired data and applied for ethics. MC handled the GC–MS. XN and YH collected the clinical samples and were part of the study. All authors contributed to the review of the manuscript and approved the final version for publication.

Corresponding authors

Correspondence to Shijia Liu, Xiaowei Nie or Wei Zhou.

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Conflict of interest

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Ethical approval

All procedures were approved by the medical ethics committee of the Affiliated Hospital of Nanjing University of Chinese Medicine and followed the tenets of the Declaration of Helsinki (2018NL-106-02).

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Zhang, Z., Hong, Y., Chen, M. et al. Serum metabolomics reveals metabolic profiling for women with hyperandrogenism and insulin resistance in polycystic ovary syndrome. Metabolomics 16, 20 (2020). https://doi.org/10.1007/s11306-020-1642-y

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