TNF and obesity due to melanocortin 4 receptor deficiency: Additionally, the elevated circulating LPS levels in obesity serve as additional systemic inflammatory stimuli, signaling through Toll-like receptor 4 (TLR4), leading to the activation of NFκB [63,64] and STAT3 [65], and resulting in the increased production of inflammatory mediators (e.g., TNFα, IL-6, MCP-1, etc.).