TNF and obesity due to melanocortin 4 receptor deficiency: Obesity-associated hypoxia was proposed as a key initiator of AT dysregulation (Trayhurn, 2013) and meta-inflammation, through up-regulation of proinflammatory mediators in adipocytes and macrophages, such as TNFα, IL-1, IL-6, CCL2, inducible nitric oxide synthase (iNOS), and others (Quintero et al., 2012; Wood et al., 2009; Ye et al., 2007).