In obesity, Timp1 (tissue inhibitor of metalloproteinases 1), Spp1 (osteopontin/secreted phosphoprotein 1), PAI-1 (plasminogen activator inhibitor-1) and Igfbp3 (insulin-like growth factor-binding protein 3) significantly increase in adipose tissue and contribute to the insulin resistance (23-27). The gene discussed is SPP1; the disease is obesity due to melanocortin 4 receptor deficiency.