Although obesity seems a largely polygenic determinant, a number of single gene mutations (e.g., of the melanocortin 4 receptor gene, fat mass, and obesity-associated gene, leptin, and leptin receptor genes or the proopiomelanocortin gene) have been discovered which together may account for ~1% of cases of human obesity (21). Here, LEP is linked to obesity due to melanocortin 4 receptor deficiency.