Obesity is a multi-layered metabolic disorder characterized by excess fat storage and adipocyte mass, which induces: (i) local changes, including chronic low-grade inflammation and altered adipokine/cytokine’ secretion; and (ii) systemic disorders concerning an imbalance in insulin levels, abnormalities of the IGF-I axis, changes in hormone biosynthesis and pathway, impaired levels of adipokines, and inflammation-related mediators such as Interleukin (IL)-1β, and Tumor Necrosis Factor (TNF)-α and IL-6 (as reviewed in [56]). This evidence concerns the gene TNF and obesity due to melanocortin 4 receptor deficiency.