Journal Article Epublish
PubMed: 40764579 DOI: 10.1186/s12916-025-04282-w
Insulin resistance as a potential driving force of parental obesity-induced adverse metabolic programming mechanisms in children with obesity.
BMC Med 23(1):458
Authors: Lucía Jurado-Sumariva, Álvaro González-Domínguez, Otto Savolainen, Jesús Domínguez-Riscart, Rikard Landberg, Raúl González-Domínguez
Affiliations
- Instituto de Investigación e Innovación Biomédica de Cádiz (INiBICA), Hospital Universitario Puerta del Mar, Universidad de Cádiz, Cádiz, 11009, Spain.
- Instituto de Investigación e Innovación Biomédica de Cádiz (INiBICA), Hospital Universitario Puerta del Mar, Universidad de Cádiz, Cádiz, 11009, Spain.
- Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York City, NY, 10029, USA.
- Division of Food and Nutrition Science, Department of Life Sciences, Chalmers University of Technology, Gothenburg, SE-412 96, Sweden.
- Unidad de Endocrinología Pediátrica y Diabetes, Servicio de Pediatría, Hospital Universitario Puerta del Mar, Cádiz, 11009, Spain.
- Instituto de Investigación e Innovación Biomédica de Cádiz (INiBICA), Hospital Universitario Puerta del Mar, Universidad de Cádiz, Cádiz, 11009, Spain.
Abstract
BACKGROUND
Parental obesity has been identified as one of the most important early risk factors for childhood obesity, but molecular mechanisms driving this greater predisposition remain to be elucidated.
METHODS
In this study, we recruited a cohort comprising children with obesity (body mass index over two z-scores above the age/sex-adjusted mean of the Spanish reference population, age range: 6-12 years), born to parents with obesity (N = 18) or without obesity (N = 41), as well as matched healthy controls (N = 26). Plasma and erythrocyte samples were collected for comprehensive biochemical and metabolomics analyses, this latter by applying high-throughput liquid chromatography-mass spectrometry. Then, a combination of multivariate and univariate statistical tools was applied to unravel the molecular pathogenic impairments that parental obesity may imprint in the offspring.
RESULTS
Interestingly, we found parental obesity to be associated with exacerbated unhealthy metabolic outcomes in the offspring with obesity, as mirrored in higher fasting insulin levels (p = 2.8 × 10 -8) and HOMA-IR scores (p = 1.3 × 10 -8). This was in turn accompanied by altered concentrations in 87 plasma and 51 erythroid metabolites (p < 0.05) involved in a variety of obesity-related pathways that are known to be tightly regulated by insulin action, namely energy-related metabolism, branched-chain amino acids, nitrogen homeostasis, redox systems, and steroid synthesis (i.e., steroid hormones, bile acids). Additional analyses demonstrated that most metabolomics associations were largely attenuated after adjusting for the HOMA-IR scores.
CONCLUSIONS
Therefore, we hypothesize that insulin resistance could be a major driving force in mediating deleterious programming mechanisms induced by parental obesity in the offspring.
MeSH
Insulin Resistance, Insulin, Metabolomics, Obesity, Steroids, Child