It is reasonable to suggest that obesity-induced low-grade inflammation, chronic lipolysis, increased FFA and insulin levels are a driving force responsible for the key pathogenic shift from lipogenesis to local activation of the catabolic program, in part lipolysis-stimulated IR and hepatic gluconeogenesis, promoting hyperglycemia through increased glycerol and FFA delivery to the liver [25]. This evidence concerns the gene INS and obesity due to melanocortin 4 receptor deficiency.