ESPE Yearbook of Paediatric Endocrinology

Nat Med. 2025 Jan;31(1):294-305. PMID: 39304782. doi: 10.1038/s41591-024-03279-x. https://pubmed.ncbi.nlm.nih.gov/39304782/

Brief Summary: This cross-sectional study offers a significant contribution to pediatric metabolic research by using comprehensive lipidomics to identify early, modifiable biomarkers of cardiometabolic risk. In a cohort of 1,331 children (including 958 with overweight or obesity), the study found a distinct lipidomic signature that was strongly associated with insulin resistance, hepatic steatosis, and hypertension. Some associations not only persisted after adjusting for BMI, highlighting the added predictive value of lipid profiling, but also changed in response to a one-year family-based lifestyle intervention, demonstrating responsiveness to behavioural change. A specific 3-lipid panel predicted hepatic steatosis with high accuracy, rivalling or surpassing traditional liver enzyme tests.

This work builds on a growing body of adult literature linking ceramides and other lipid classes to metabolic and cardiovascular diseases [1-4]. However, few studies have translated these findings to pediatric populations [5-8]. Huang et al. bridge this gap by demonstrating that lipid profiles not only correlate with current metabolic risk but also change in response to lifestyle intervention.

Study strengths include its large sample size, advanced analytical techniques, and integration of both cross-sectional and longitudinal data. Limitations include lack of causal inference due to its observational design and limited demographic and ethnic diversity. Nonetheless, it advances the field by identifying modifiable lipid signatures with potential as early indicators and therapeutic targets. Future research should focus on validating these biomarkers in more diverse populations and integrating them into clinical screening protocols.

References: 1. Rauschert S, Uhl O, Koletzko B, Kirchberg F, Mori TA, Huang RC, Beilin LJ, Hellmuth C, Oddy WH. Lipidomics Reveals Associations of Phospholipids With Obesity and Insulin Resistance in Young Adults. J Clin Endocrinol Metab. 2016 Mar;101(3):871-9. PMID: 26709969.2. Guo K, Savelieff MG, Rumora AE, Alakwaa FM, Callaghan BC, Hur J, Feldman EL. Plasma Metabolomics and Lipidomics Differentiate Obese Individuals by Peripheral Neuropathy Status. J Clin Endocrinol Metab. 2022 Mar 24;107(4):1091-1109. PMID: 34878536.3. Bellot PENR, Braga ES, Omage FB, da Silva Nunes FL, Lima SCVC, Lyra CO, Marchioni DML, Pedrosa LFC, Barbosa F Jr, Tasic L, Sena-Evangelista KCM. Plasma lipid metabolites as potential biomarkers for identifying individuals at risk of obesity-induced metabolic complications. Sci Rep. 2023 Jul 20;13(1):11729. PMID: 37474543.4. Yu B, Hu M, Jiang W, Ma Y, Ye J, Wu Q, Guo W, Sun Y, Zhou M, Xu Y, Wu Z, Wang Y, Lam SM, Shui G, Gu J, Li JZ, Fu Z, Gong Y, Zhou H. Ceramide d18:1/24:1 as a potential biomarker to differentiate obesity subtypes with unfavorable health outcomes. Lipids Health Dis. 2023 Oct 4;22(1):166. PMID: 37794463.5. Yin R, Wang X, Li K, Yu K, Yang L. Lipidomic profiling reveals distinct differences in plasma lipid composition in overweight or obese adolescent students. BMC Endocr Disord. 2021 Oct 13;21(1):201. PMID: 34641844.6. Liang X, Tang X, Xi B, Qu P, Ren Y, Hao G. Abdominal obesity-related lipid metabolites may mediate the association between obesity and glucose dysregulation. Pediatr Res. 2023 Jan;93(1):183-188. z. PMID: 35437306.7. Sharma S, Subrahmanyam YV, Ranjani H, Sidra S, Parmar D, Vadivel S, Kannan S, Grallert H, Usharani D, Anjana RM, Balasubramanyam M, Mohan V, Jerzy A, Panchagnula V, Gokulakrishnan K. Circulatory levels of lysophosphatidylcholinespecies in obese adolescents: Findings from cross-sectional and prospective lipidomics analyses. Nutr Metab Cardiovasc Dis. 2024 Jul;34(7):1807-1816. PMID: 38503619.8. García-Hermoso A, Huerta-Uribe N, Izquierdo M, González-Ruíz K, Correa-Bautista JE, Ramírez-Vélez R. Comparative lipidomic profiling in adolescents with obesity and adolescents with type 1 diabetes. Curr Probl Cardiol. 2025 Mar;50(3):102991. PMID: 39828111.