TNF and obesity due to melanocortin 4 receptor deficiency: From a pathophysiological point of view, MS and obesity have at least three distinctive pathways in common that are not mutually exclusive but may overlap: (1) chronic inflammation (i.e., increased circulating levels of TNF-α, IL-6, IL-1β, IFN-γ, and many others [31,32]), (2) endocrine alterations (disturbed secretion of adipokines), and (3) alterations in the gut microbiome (extensively reviewed elsewhere [33]).