Although obesity in PWS was found to be unrelated to defective leptin production and/or a deficiency in the leptin receptor [56], [57], the hyperleptinemia found in adults with PWS, reflecting the increase in total adipose tissue mass, may in fact lead to the development of leptin resistance, as observed in the general obese population. This evidence concerns the gene LEP and obesity due to melanocortin 4 receptor deficiency.