Other potential pathways by which obesity might induce IR include the action of retinol-binding protein-4 (RBP4) which reduces phosphatidylinositol-3-OH kinase (PI(3)K) signalling in muscle and enhances expression of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase in the liver [39]. This evidence concerns the gene RBP4 and obesity due to melanocortin 4 receptor deficiency.