There is growing scientific evidence that the risk of developing metabolic diseases, such as obesity, can begin before birth – during pregnancy – through subtle changes in gene function, known as epigenetic modifications. In this context, the Maternal-Fetal Metabolic Research Group of the Girona Biomedical Research Institute Dr. Josep Trueta (IDIBGI) has led a study analyzing whether epigenetic changes in the placenta could help predict childhood obesity.

The research was recently published in the journal “International Journal of Molecular Sciences”, with postdoctoral researcher Dr. Ariadna Gómez and predoctoral researcher Maria Niubó as first co-authors, and the group leader Dr. Judit Bassols as last author.

The study analyzed DNA methylation, a type of epigenetic modification that regulates gene activation or silencing and can alter gene expression. Specifically, 24 placenta samples were used to study DNA methylation marks associated with a higher risk of childhood obesity [higher body mass index (BMI) at 6 years of age]. The IRS1 gene (Insulin Receptor Substrate 1), which encodes a key protein in the insulin signaling pathway, emerged as a candidate and was further studied in a larger cohort of 147 placenta samples and also in the children’s blood at 6 years of age.

“Our results show that the methylation levels of the IRS1 gene, both in the placenta and in the blood of children, are associated with various indicators of metabolic risk,” says Dr. Gómez. Furthermore, using artificial intelligence models, the research team shows that methylation of this gene in the placenta can accurately predict which children are more likely to develop obesity in childhood.

These findings suggest that the IRS1 gene could serve as an early epigenetic marker for identifying children at higher risk of developing metabolic disorders. This could pave the way for much earlier and more personalized prevention strategies.

The study also involved the Pediatric Endocrinology Research Group at IDIBGI, led by Dr. Abel López-Bermejo, and a team from the Sant Joan de Déu Research Institute, led by Dr. Lourdes Ibáñez. This research was supported by grants from the Ministerio de Ciencia e Innovación and the Instituto de Salud Carlos III (ISCIII), Madrid, Spain (PI20/00399 and PI23/00545), as part of a project co-funded by the FEDER (European Regional Development Fund).

Reference article: Gómez-Vilarrubla A, Niubó-Pallàs M, Mas-Parés B, Bonmatí-Santané A, Martínez-Calcerrada JM, López B, Peñas-Cruz A, de Zegher F, Ibáñez L, López-Bermejo A, Bassols J. Longitudinal Analysis of Placental IRS1 DNA Methylation and Childhood Obesity. Int J Mol Sci. 2025 Mar 28;26(7):3141. doi: 10.3390/ijms26073141. PMID: 40243885; PMCID: PMC11988732.