INS and obesity due to melanocortin 4 receptor deficiency: It was reported that in animal models of obesity/insulin resistance, treatment with recombinant TNF-α receptor protein resulted in a 2- to 3-fold increase in insulin sensitivity [15, 16], and no insulin resistance was observed in obese mice that knocked out TNF-α or TNF-α receptors, indicating that adipose tissue-derived TNF-α is a major contributor of obesity-induced insulin resistance [17, 18].