Determinants of Plasma HDL-Cholesterol Concentrations in Prepubertal Children: Insights from Two Decades of Research in a Spanish Pediatric Cohort
- 1Lipid Research Laboratory, Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD, UAM), 28040 Madrid, Spain
- 2Department of Chemistry and Biochemistry, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, 28660 Madrid, Spain
- 3Department of Pediatrics, Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD, UAM), 28040 Madrid, Spain
Abstract
High-density lipoprotein cholesterol (HDL-C) is a well-established cardiovascular risk marker; however, its determinants in childhood remain incompletely understood. The prepubertal period provides a useful window for studying the determinants of HDL-C because it is free of confounders present in other age groups. In this review, we summarize the findings on the plasma HDL-C determinants in Spanish prepubertal children aged 6–8 years from decades of research in the Four Provinces Study. Children with obesity had lower HDL-C concentrations, but BMI was only weakly associated with HDL-C, whereas markers of adipose tissue function, particularly leptin, showed stronger and potential sex-dependent associations. Among common variants in genes directly involved in HDL metabolism, CETP TaqIB emerged as the main genetic predictor, although it explained less than 5% of HDL-C variability. Variants in genes related to adipose-tissue biology (LEP, PLIN1, PLIN2 and DLK1) were also associated with HDL-C in a sex-specific manner, and some associations were modulated by circulating leptin. Dietary intake made only a modest contribution to HDL-C variability, yet fat intake modified the effect of the LIPC −514C>T variant on HDL-C. Overall, these findings support an integrated adipose tissue–HDL axis in childhood and suggest that sex may influence this relationship even before puberty.
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BibTeX
@article{pomares2026determinants,
title = {{Determinants of Plasma HDL-Cholesterol Concentrations in Prepubertal Children: Insights from Two Decades of Research in a Spanish Pediatric Cohort}},
author = {Olga Pomares and Henar Ortega-Senovilla and Leandro Soriano-Guillén and Carmen Garcés},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = nov,
doi = {10.3390/ijms27219984},
url = {https://www.mdpi.com/1422-0067/27/21/9984},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Determinants of Plasma HDL-Cholesterol Concentrations in Prepubertal Children: Insights from Two Decades of Research in a Spanish Pediatric Cohort
AU - Olga Pomares
AU - Henar Ortega-Senovilla
AU - Leandro Soriano-Guillén
AU - Carmen Garcés
PY - 2026
DA - 2026/11/07
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219984
UR - https://www.mdpi.com/1422-0067/27/21/9984
AB - High-density lipoprotein cholesterol (HDL-C) is a well-established cardiovascular risk marker; however, its determinants in childhood remain incompletely understood. The prepubertal period provides a useful window for studying the determinants of HDL-C because it is free of confounders present in other age groups. In this review, we summarize the findings on the plasma HDL-C determinants in Spanish prepubertal children aged 6–8 years from decades of research in the Four Provinces Study. Children with obesity had lower HDL-C concentrations, but BMI was only weakly associated with HDL-C, whereas markers of adipose tissue function, particularly leptin, showed stronger and potential sex-dependent associations. Among common variants in genes directly involved in HDL metabolism, CETP TaqIB emerged as the main genetic predictor, although it explained less than 5% of HDL-C variability. Variants in genes related to adipose-tissue biology (LEP, PLIN1, PLIN2 and DLK1) were also associated with HDL-C in a sex-specific manner, and some associations were modulated by circulating leptin. Dietary intake made only a modest contribution to HDL-C variability, yet fat intake modified the effect of the LIPC −514C>T variant on HDL-C. Overall, these findings support an integrated adipose tissue–HDL axis in childhood and suggest that sex may influence this relationship even before puberty.
SN - 1422-0067
ER -