It was proposed by Frasca and Blomberg (184) that increased hypoxia and CCL-2 expression, along with increased adipocyte-derived TNF-α, IFN-γ, IL-6, and IL-21, prompted an obesity-driven accumulation of pro-inflammatory B-cells, which is exacerbated with ageing (184). The gene discussed is TNF; the disease is obesity due to melanocortin 4 receptor deficiency.