PCOS combined with obesity aggravates the metabolic and immune abnormality in females.

INTRODUCTION: Polycystic ovary syndrome (PCOS) appears to be closely correlated with obesity; however, no studies have compared the difference between PC-Ob (PCOS plus obesity), obesity-only, and PCOS-only patients at a multi-omics level. In the present study, we aimed to explore this through sEV proteomics and metabolomics on female plasma. METHODS: We recruited 79 females based on BMI, AMH, LH, T, P, Fasting insulin, and HOMA-IR; next, we categorized them into four groups: 20 Control (Ctr), 21 PCOS, 19 Obesity (Ob), and 19 PCOS with Obesity (PC-Ob) and collected plasma samples. Next, we randomly sent 10 from each group for quantitative sEV proteomics and untargeted metabolomics on female plasma. RESULTS: There were significant changes in multiple metabolites and proteins between each of three patient (PCOS, Ob, and PC-Ob) groups and Ctr group. Particularly, compared with PCOS or Ob group, PC-Ob group have more DEPs (differentially-expressed proteins) and MLDs (metabolites with level difference), and the proteins are largely involved in immunity and metabolism. Cross-omics associations analysis showed that two immunity and metabolism-related DEPs, A2M and BCHE, changes in high correlation with multiple lipids between the upper four groups. DISCUSSION: Our findings showed that females with both PCOS and obesity have significantly increased abnormalities in immunity and metabolism.