Concordantly, 4E-BP1 overexpression or activation has been linked to increased glucose tolerance in mice while knockout of 4E-BP1 and 4E-BP2 in mice results in insulin resistance, increased sensitivity to diet-induced obesity, and increased muscle lean mass and lipid accumulation [17–20]. This evidence concerns the gene EIF4EBP1 and obesity due to melanocortin 4 receptor deficiency.