INS and obesity due to melanocortin 4 receptor deficiency: In lean/healthy animals, mTORC1 critically mediates insulin signaling in metabolic tissues (to coordinate postprandial nutrient storage), but in obesity, chronic nutrient excess leads to an aberrant increase in mTORC1 activity that contributes directly to insulin resistance and metabolic dysregulation (Laplante and Sabatini, 2012).