Epigenetic regulation in pediatric obesity: adipose tissue microRNA profiling across pubertal development and insulin resistance

Background: Paediatric obesity is a growing global health problem associated with early metabolic complications, yet the molecular mechanisms underlying adipose tissue dysfunction during childhood remain insufficiently defined. MicroRNAs (miRNAs) are key post-transcriptional regulators and may represent early biomarkers of metabolic risk, with a role in adipogenesis, inflammation, and insulin signalling. Methods: This study investigated the expression of 10 obesity-related miRNAs and four target genes in subcutaneous adipose tissue from 29 children classified as normal weight (NW) or overweight/obese (OW/OB). Quantitative RT-qPCR and integrative statistical analyses were used to explore associations with anthropometric, metabolic, and developmental parameters, including pubertal stage and insulin resistance (HOMA-IR). Results: OW/OB children displayed a distinct miRNA–gene expression profile that clearly differentiated them from NW subjects. In particular, miR-22-5p and inflammatory markers (IL-6, VEGFA) were significantly upregulated in OW/OB samples, suggesting early adipose tissue remodelling. Correlation analyses revealed physiological associations between miRNAs and growth or lipid parameters in NW children that were largely disrupted in OW/OB. In lean subjects, miR-221 and miR-26b correlated with developmental and lipid variables, whereas in OW/OB children miR-130a-3p, miR-34a, and let-7d were linked to pubertal stage and insulin resistance. Stratification by Tanner stage highlighted a specific molecular signature in prepubertal OW/OB children, indicating that puberty represents a critical window for obesity-related epigenetic remodelling. Notably, several miRNA alterations were detectable in OW/OB children without overt insulin resistance, suggesting that adipose tissue molecular dysregulation precedes systemic metabolic impairment. Conclusions: These findings identify a puberty- and insulin-resistance-modulated miRNA signature in paediatric adipose tissue and support the potential use of miRNAs as early biomarkers of metabolic risk and targets for precision-medicine approaches in childhood obesity.