In contrast, obesity- and T2D-related disorders, such as increased production of FFAs and intracellular lipid deposition, mitochondrial dysfunction and increased oxidative stress, and increased production of proinflammatory cytokines, may promote insulin resistance by acting at different points of the PI3K/Akt pathway, especially in skeletal muscle, where the majority of insulin-stimulated glucose utilization takes place [104]. This evidence concerns the gene PIK3CG and obesity due to melanocortin 4 receptor deficiency.