Canonical NF-κB Pathway as a Central Regulator of Obesity-Associated Inflammation: A Narrative Review.

Obesity is characterized by a chronic inflammation driven primarily by sustained activation of the canonical NF-κB signaling pathway. This persistent inflammatory state originates in hypertrophic adipose tissue and progressively affects multiple organ systems, contributing to systemic metabolic dysfunction. This review explores the molecular architecture and regulatory components of the canonical NF-κB pathway and outline how metabolic stressors, cytokines, chemokines, adhesion molecules, and dysregulated microRNAs influence its activity in obesity. Clinically relevant NF-κB linked biomarkers are characterized, those that reflect the degree of inflammation and may support risk stratification in metabolic disease. Finally, we discuss emerging therapeutic strategies, including small-molecule inhibitors, monoclonal antibodies, and miRNA-based approaches designed to modulate NF-κB activity while preserving its essential physiological roles. Together, these insights emphasize the central involvement of NF-κB in obesity-associated inflammation and highlight potential targets for selective intervention.