TNF and obesity due to melanocortin 4 receptor deficiency: Metabolic disorder and inflammation cause IR and promote leukocytes to secrete proinflammatory cytokines, including IL-6 and tumor necrosis factor-α (TNF-α) (Feve and Bastard, 2009; Wen et al., 2011; Wensveen et al., 2015), which provides a framework to understand how physiological stress, obesity, and diet promote IR.