Epigenetic insights into pediatric obesity: microRNA profiling across puberty and insulin resistance-related stratification.

OBJECTIVE: Pediatric obesity is a major global health challenge due to its increasing prevalence and elevated risk of early metabolic disease, yet the molecular mechanisms underlying adipose tissue dysfunction in childhood remain poorly understood. METHODS: In this cohort-based study, we profiled the expression of 10 obesity-associated microRNAs (miRNAs) and four target genes in subcutaneous adipose tissue from 29 children classified as normal-weight (NW) or overweight/obese (OW/OB). Molecular data were integrated with anthropometric, pubertal, and metabolic parameters, including the homeostatic model assessment for insulin resistance (HOMA-IR) as a fasting surrogate index of insulin resistance. RESULTS: OW/OB children exhibited a distinct miRNA and gene expression signature that accurately discriminated them from NW subjects. Physiological correlations between miRNAs and clinical parameters observed in NW were largely disrupted in OW/OB. In NW children, miR-221 and miR-26b correlated with growth and lipid parameters, whereas in OW/OB children miR-130a-3p, miR-34a and let-7d associated with pubertal stage and HOMA-IR. Pubertal stratification revealed distinct molecular profiles in prepubertal OW/OB subjects, identifying puberty as a critical window for obesity-related molecular remodeling. Notably, miRNA alterations were detectable in OW/OB children in the lower HOMA-IR stratum, suggesting that adipose tissue molecular dysregulation precedes systemic metabolic impairment. CONCLUSION: These findings identify a puberty- and HOMA-IR-associated miRNA signature in pediatric adipose tissue, highlighting early epigenetic remodeling in obesity. Because these signatures were identified in adipose tissue, future studies should determine whether comparable molecular profiles can also be detected in blood before any clinical application is considered. This molecular profile may represent a promising candidate for investigation in early risk stratification and targeted intervention in pediatric populations.