Predictive epigenetic biomarkers of successful weight-loss intervention in pre-pubertal children with obesity.

Childhood obesity represents a major public health challenge, increasing long-term risks such as type 2 diabetes and cardiovascular disease. Lifestyle interventions in prepubertal children are often more effective, but individual responses can vary, highlighting the need for predictive biomarkers to personalize treatment. This study investigated DNA methylation profiles in prepubertal children living with obesity to identify possible epigenetic markers that could predict the success of weight loss interventions. We analyzed a cohort of 26 children who underwent a six-month lifestyle intervention focused on dietary modifications. From 214 differentially methylated CpG sites between high and low responders, we narrowed these to eight key markers. These markers were used to develop a predictive model with a precision 84% in classifying children based on their BMI normalized to changes in the z-score of the age. CpGs were found in genes such as GSDMD, GFRA1 and NRP2, all linked to pathways involved in inflammation, metabolic regulation, and lipid metabolism, which are crucial in the development of obesity. The results suggest that DNA methylation signatures can predict weight loss responses in prepubertal children, offering a novel approach to early-stage obesity intervention. These findings hold promise for the development of personalized treatment strategies in pediatric obesity. However, larger and more diverse cohort studies are needed to confirm the generalizability of these markers and refine the predictive model for broader clinical use.