MODERN IMMUNOLOGICAL AND BIOMOLECULAR FOUNDATIONS OF METABOLIC SYNDROME IN CHILDREN

Metabolic syndrome in children is a multifactorial disorder characterized by obesity, insulin resistance, and other cardiometabolic risk factors, the pathogenesis of which involves complex immunological and biomolecular mechanisms. Chronic low-grade inflammation and immune system dysregulation are hallmarks of the condition, fostering insulin resistance and vascular dysfunction. Among the key molecular signaling pathways implicated in this process, the nuclear factor-kappa B (NF-κB) cascade and the NLRP3 inflammasome are aberrantly activated in adipose tissue, linking nutrient excess to inflammatory responses. Toll-like receptor 4 (TLR4) serves as a critical upstream sensor connecting innate immune signaling with metabolic stress, triggering NF-κB activation and promoting fatty acid–induced insulin resistance. This sustained innate immune activation leads to overproduction of pro-inflammatory cytokines (e.g., TNF-α, IL-1β) and altered adipokine profiles, whereby leptin levels rise while adiponectin falls — an imbalance that further exacerbates subclinical inflammation and insulin resistance. Genetic predispositions — such as polymorphisms in immunoregulatory genes (e.g., NLRP3, STAT3) — and epigenetic modifications, including diet-induced changes in DNA methylation and gene expression, further shape these immune–metabolic interactions. Emerging evidence in pediatric populations underscores that immunometabolic crosstalk — encompassing adipose tissue macrophage infiltration and adipokine signaling — contributes to the early development of metabolic syndrome. Understanding these mechanisms provides a foundation for identifying biomarkers and developing targeted interventions to prevent or mitigate pediatric metabolic syndrome and its long-term cardiometabolic complications.

Hali tarjima qilinmagan