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Peer-reviewedCC BY 4.0Metabolites

Pediatric Obesity and Cardiometabolic Health: Integrating Metabolomic Signatures, Biological Mechanisms, and Early-Life Exposures

  • Julio Plaza-Diaz1,2,3
  • Lourdes Herrera-Quintana4
  • Carlos Torres-Villar5,6
  • Jorge Olivares-Arancibia7
  • Lucía Iglesias-Vázquez1,2,3
7 affiliations
  1. 1Departament de Bioquímica i Biotecnologia, ANUT-DSM (Alimentaciò, Nutrició Desenvolupament i Salut Mental), Universitat Rovira i Virgili, 43201 Reus, Spain
  2. 2Institut de Recerca Biomèdica Catalunya Sud, Hospital Universitari Sant Joan de Reus, 43204 Reus, Spain
  3. 3Biomedical Research Networking Center for Physiopathology of Obesity and Nutrition (CIBERObn), Institute of Health Carlos III, 28029 Madrid, Spain
  4. 4Laboratory of Cellular and Molecular Gerontology, Precision Nutrition and Aging, Madrid Institute for Advanced Studies—IMDEA Nutrition, CEI UAM+CSIC, 28049 Madrid, Spain
  5. 5⁠Doctoral Program in Morphological Sciences, Faculty of Medicine, Universidad de La Frontera, Temuco 4780000, Chile
  6. 6Departamento de Ciencias Morfológicas, Facultad de Ciencias, Universidad San Sebastián, Puerto Montt 5501842, Chile
  7. 7AFySE Group, Research in Physical Activity and School Health, School of Physical Education, Faculty of Education, Universidad de Las Américas, Santiago 8370040, Chile
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Abstract

Pediatric obesity is increasingly recognized as a biologically heterogeneous metabolic condition associated with early alterations in cardiometabolic health. Traditional clinical markers provide limited resolution for characterizing this heterogeneity, underscoring the need for more integrative approaches. Metabolomics has emerged as a powerful tool for identifying molecular phenotypes that reflect the interplay between excess adiposity, environmental and lifestyle exposures, and cardiometabolic dysfunction. This narrative review synthesizes current evidence on pediatric obesity and cardiometabolic health, with particular emphasis on metabolomic signatures, potential biological mechanisms, and early-life and lifestyle determinants. Studies using nuclear magnetic resonance spectroscopy and mass spectrometry have identified coordinated alterations in lipoprotein subclasses, triglyceride-rich particles, fatty acids and complex lipids, branched-chain and aromatic amino acids, acylcarnitines, and pathways involved in energy metabolism. These metabolic profiles are associated with insulin resistance and other adverse cardiometabolic traits. Proposed links with adipose tissue dysfunction, inflammation, mitochondrial substrate utilization, and hepatic lipid dysregulation draw partly on adult and experimental mechanistic evidence. Early-life and lifestyle exposures, including maternal health, infant feeding, dietary patterns, physical activity, sleep, and environmental factors, may further shape these metabolic phenotypes. Integrating metabolomic information with clinical and environmental data may improve the characterization of metabolic heterogeneity and help identify biological pathways associated with early cardiometabolic dysfunction. However, classification of current metabolic phenotypes does not establish prediction of future disease. Independent prospective validation, methodological harmonization, and demonstration of incremental clinical utility remain necessary before metabolomic profiling can be incorporated into routine pediatric risk assessment.

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Cite

BibTeXRIS
BibTeX
@article{plazadiaz2026pediatric,
  title = {{Pediatric Obesity and Cardiometabolic Health: Integrating Metabolomic Signatures, Biological Mechanisms, and Early-Life Exposures}},
  author = {Julio Plaza-Diaz and Lourdes Herrera-Quintana and Carlos Torres-Villar and Jorge Olivares-Arancibia and Lucía Iglesias-Vázquez},
  journal = {Metabolites},
  year = {2026},
  month = nov,
  doi = {10.3390/metabo16110846},
  url = {https://www.mdpi.com/2218-1989/16/11/846},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Pediatric Obesity and Cardiometabolic Health: Integrating Metabolomic Signatures, Biological Mechanisms, and Early-Life Exposures
AU  - Julio Plaza-Diaz
AU  - Lourdes Herrera-Quintana
AU  - Carlos Torres-Villar
AU  - Jorge Olivares-Arancibia
AU  - Lucía Iglesias-Vázquez
PY  - 2026
DA  - 2026/11/03
JO  - Metabolites
DO  - 10.3390/metabo16110846
UR  - https://www.mdpi.com/2218-1989/16/11/846
AB  - Pediatric obesity is increasingly recognized as a biologically heterogeneous metabolic condition associated with early alterations in cardiometabolic health. Traditional clinical markers provide limited resolution for characterizing this heterogeneity, underscoring the need for more integrative approaches. Metabolomics has emerged as a powerful tool for identifying molecular phenotypes that reflect the interplay between excess adiposity, environmental and lifestyle exposures, and cardiometabolic dysfunction. This narrative review synthesizes current evidence on pediatric obesity and cardiometabolic health, with particular emphasis on metabolomic signatures, potential biological mechanisms, and early-life and lifestyle determinants. Studies using nuclear magnetic resonance spectroscopy and mass spectrometry have identified coordinated alterations in lipoprotein subclasses, triglyceride-rich particles, fatty acids and complex lipids, branched-chain and aromatic amino acids, acylcarnitines, and pathways involved in energy metabolism. These metabolic profiles are associated with insulin resistance and other adverse cardiometabolic traits. Proposed links with adipose tissue dysfunction, inflammation, mitochondrial substrate utilization, and hepatic lipid dysregulation draw partly on adult and experimental mechanistic evidence. Early-life and lifestyle exposures, including maternal health, infant feeding, dietary patterns, physical activity, sleep, and environmental factors, may further shape these metabolic phenotypes. Integrating metabolomic information with clinical and environmental data may improve the characterization of metabolic heterogeneity and help identify biological pathways associated with early cardiometabolic dysfunction. However, classification of current metabolic phenotypes does not establish prediction of future disease. Independent prospective validation, methodological harmonization, and demonstration of incremental clinical utility remain necessary before metabolomic profiling can be incorporated into routine pediatric risk assessment.
SN  - 2218-1989
ER  -