As reviewed by Newgard [25], increased circulating levels of BCAA likely activating the mTOR pathway are associated with the incidence of higher obesity and type 2 diabetes in humans as widely evidenced during the last decades in several studies, and it has been established that high BCAA can indirectly undermine insulin sensitivity through the chronic activation of the mTOR pathway, inducing an over phosphorylation of the insulin receptor substrate [26, 27]. This evidence concerns the gene INS and obesity due to melanocortin 4 receptor deficiency.