Increased retinol-binding protein-4 (RBP4) in obesity downregulates phosphatidylinositol-3-OH kinase (PI(3)K) signaling in muscle and promotes gluconeogenic enzyme phosphoenolpyruvate carboxykinase expression in the liver through a retinol-dependent mechanism, which induces insulin resistance [125]. The gene discussed is RBP4; the disease is obesity due to melanocortin 4 receptor deficiency.