Three mechanisms linking obesity to insulin resistance include: (1) increased production of cytokines, including tumour necrosis factor-α, resistin and retinol-binding protein 4, leading to reduced levels of adiponectin and subsequent insulin resistance;32 (2) ectopic fat deposition in the liver and in the skeletal muscle;33 and (3) mitochondrial dysfunction leading to decreased insulin sensitivity. Here, INS is linked to obesity due to melanocortin 4 receptor deficiency.