TNF and obesity due to melanocortin 4 receptor deficiency: This switch from anti-inflammatory M2 Mφ, that are dominant in the adipose tissue of lean individuals, to M1 Mφ during obesity promotes the production of pro-inflammatory cytokines (e.g.,TNF-α and IL-1β) that can directly inhibit insulin signaling and lead to cardiovascular and metabolic complications related to obesity (8).