Thus, in a manner similar to other cytokines [28] and pathological situations associated with obesity-related insulin resistance, such as hypoxia [21] or hyperinsulinemia [22], ZAG produces paradoxical effects on glucose uptake in human adipocytes: it increases glucose uptake but also impairs insulin signaling, affecting insulin-stimulated glucose uptake. This evidence concerns the gene INS and obesity due to melanocortin 4 receptor deficiency.