Secoisolariciresinol Levels in Central Precocious Puberty: A Metabolomic Study on Disease Association and Obesity

Background and Objective: Obesity is a significant risk factor for Central Precocious Puberty (CPP), and dietary phytoestrogens are also implicated. This study aimed to identify differential serum metabolites in girls with CPP. Methods: This case-control study included 100 girls with CPP (CC group) and 100 healthy control girls (NN group). Serum samples were analyzed using a non-targeted metabolomics approach via UHPLC-MS/MS. Statistical analysis, including one-way ANOVA with Tukey’s HSD test, was used to identify differential metabolites. The Comparative Toxicogenomics Database (CTD) and STRING database were utilized to predict disease associations and potential protein-protein interaction (PPI) networks for key metabolites. Results: Principal Component Analysis (PCA) revealed distinct metabolic profile differences between CPP and control groups, with high system stability confirmed by quality control analysis (Pearson r > 0.99). Serum Secoisolariciresinol levels were significantly elevated in all CPP subgroups (COB, COW, C) compared to their non-CPP counterparts (NOB, NOW, N) (P < 0.0001). Within the CPP cohort, Secoisolariciresinol levels were also positively associated with BMI, being significantly higher in obese and overweight girls than in those with normal weight (P < 0.0001). Bioinformatic analysis predicted a strong link between Secoisolariciresinol and obesity and identified key protein targets including EGFR, ESR1, and IGF1R. Molecular docking subsequently confirmed a stable, high-affinity binding between Secoisolariciresinol and the active site of EGFR. Conclusion: Secoisolariciresinol shows strong potential as a biomarker for CPP, correlating with both disease status and body weight. Its predicted interactions with targets like EGFR suggest involvement in CPP pathogenesis via key signaling pathways, offering new insights for diagnosis and intervention.