NFKB1 and obesity due to melanocortin 4 receptor deficiency: On the one hand, excess lipids in adipose tissue due to obesity stimulate the local production of fetuin-A via the TLR4 and Nf-κB signaling cascade, creating a local microenvironment that stimulates M1 polarization and the release of pro-inflammatory cytokines along the same signaling axis85–87.