INS and obesity due to melanocortin 4 receptor deficiency: The first direct evidence of the connection existing between obesity, inflammation, and T2DM has been the elevation of TNF-α, a well-known proinflammatory molecule, in the plasma and adipose tissue of obese rodents, whose levels were proportional to insulin resistance, whose blockade ameliorated insulin sensitivity [83] and whose delivery recapitulated insulin resistance [84].