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

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. 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. 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. Our findings showed that females with both PCOS and obesity have significantly increased abnormalities in immunity and metabolism.