In peripheral tissues, such as the adipose tissue, of diabetes and obesity models, TNF-α release also activates stress kinases IκB kinase (IKK) and double-stranded RNA-dependent protein kinase (PKR), promoting inflammation and inducing endoplasmic reticulum stress besides insulin signaling deregulation (Hotamisligil et al., 1993; Wellen and Hotamisligil, 2005; Yang et al., 2009). This evidence concerns the gene TNF and obesity due to melanocortin 4 receptor deficiency.