Lipidomic Analysis of Serum Lipid Profiles in Idiopathic Central Precocious Puberty and the Potential Regulatory Role of GnRHa in Lipid Metabolism

Abstract

Idiopathic central precocious puberty (ICPP) is an endocrine disorder increasingly observed in children, commonly treated with gonadotropin-releasing hormone agonists (GnRHa). However, the serum lipid profiles in girls with ICPP and the potential regulatory effects of GnRHa in lipid metabolism remain unclear. This research analyzed lipidomic profiles of serum samples from girls younger than 10 years of age, including 37 patients with ICPP, 32 ICPP patients treated with GnRHa, and 30 age-matched healthy controls. Using UHPLC-Q-Exactive Orbitrap/MS, we identified a total of 898 differential lipids in both positive and negative modes, covering classes such as phosphatidylcholine (PC, including EtherPC), acylcarnitine (CAR), triglyceride (TG), N-acyl ethanolamines (NAEs), diacylglycerol (DG), sphingomyelin (SM), phosphatidylethanolamine (PE), ceramide (Cer), and fatty acids (FAs). In the ICPP cohort, 105 lipids exhibited significant differences compared with controls, with increased levels of CAR, SM, PC, PE, TG, and FA (p < 0.05), and notably decreased NAE levels (p < 0.05). Specifically, NAE 20:1 (AUC: 1.0), NAE 18:2 (AUC: 0.948), and NAE 20:0 (AUC: 0.895) were identified as potential diagnostic biomarkers for ICPP. Following GnRHa treatment, serum peak LH and FSH levels decreased, alongside reversible changes in 44 lipids, predominantly CAR, NAE, and TG. In conclusion, this study demonstrates that ICPP is associated with significant alterations in lipid metabolism. The lipidomic changes induced by GnRHa therapy suggest a potential link between ICPP treatment and lipid homeostasis, which warrants further investigation to refine therapeutic approaches for ICPP and potentially mitigate associated metabolic disorders.