To explore the role of the canonical NF-κB signaling pathway as a central regulator of obesity-associated inflammation, a structured and comprehensive literature search was conducted across several major scientific databases, including PubMed, Scopus, Web of Science, Google Scholar, MDPI, Nature Publishing Group, Elsevier, and SpringerLink. This evidence concerns the gene NFKB1 and obesity due to melanocortin 4 receptor deficiency.