Lipidomics reveals ceramide biomarkers for detecting central precocious puberty in girls - 09/08/24

Doi : 10.1016/j.orcp.2024.07.005

Ngan Thi Kim Nguyen ^a,^b, Shih-Yi Huang ^b,^c,^d, Hsien-Yu Fan ^b,^e, Te-Hsuan Tung ^b, Quynh Thi Vu Huynh ^f,^g, Chen Yang ^h, Yang Ching Chen ^b,^c,^d,^i,^j,^⁎,^{^{1
ORCID ID: 0000–0002-0682–3716}}
^a Undergraduate and Graduate Programs of Nutrition Science, College of Life Science, National Taiwan Normal University, Taipei, Taiwan
^b School of Nutrition and Health Sciences, Taipei Medical University, Taipei, Taiwan
^c Graduate Institute of Metabolism and Obesity Sciences, Taipei Medical University, Taipei, Taiwan
^d Nutrition Research Center, Taipei Medical University Hospital, Taipei, Taiwan
^e Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan
^f Department of Pediatrics, Faculty of Medicine, University of Medicine and Pharmacy at Ho Chi Minh city, Vietnam
^g Department of Nephrology and Endocrinology, Children’s Hospital 2, Ho Chi Minh city, Vietnam
^h Department of Pediatrics, Taipei Medical University Hospital, Taipei, Taiwan
ⁱ Department of Family Medicine, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan
^j Department of Family Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

^⁎Corresponding author at: Department of Family Medicine, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan.Department of Family Medicine, Wan Fang Hospital, Taipei Medical UniversityTaipei116Taiwan

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Abstract

Background

Pubertal timing is modulated by complex interactions between the pituitary and gonadal sex steroid hormones. Evidence indicates that sphingolipids are involved in the biosynthesis of steroid hormones at multiple levels.

Method

This study recruited adolescent female patients from pubertal and pediatric endocrine clinics in Northern and Southern Taiwan from the Taiwan Puberty Longitudinal Study. A total of 112 plasma samples (22 healthy control, 29 peripheral precocious puberty (PPP), and 61 CPP samples) were collected. We extracted lipids from the plasma samples using the modified Folch method. The un-targeted ultrahigh-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was employed for the lipid analysis.

Results

We identified sphingolipid-linked metabolites, including Cer(18:0/15:0), Cer(18:1/16:0), and Cer(18:1/26:0) as candidate biomarkers for distinguishing girls with CPP from the control group by using an excellent discrimination model (AUC = 0.964). Moreover, Cer(18:0/22:0) and Cer(d18:0/18:1) were identified as potential biomarkers of PPP, with an AUC value of 0.938. Furthermore, CerP(18:1/18:0) was identified as the sole candidate biomarker capable of differentiating CPP from PPP.

Conclusions

The biomarkers identified in this study can facilitate the accurate detection of CPP in girls, provide insights into lipid-linked pathophysiology, and present a novel method of monitoring the progression of this disorder.

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Abbreviations : AUC, CPP, Cer, CerP, C1P, FSH, FDR, GH, GluCer, hCG, KEGG, LH, LacCer, S1P, SM, TPLS, PLS-DA, PPP, ROC, UPLC-MS/MS, VIP