The role of agouti-related protein in regulating body weight

Defects in signaling by leptin, a hormone produced primarily by adipose tis sue that informs the brain of the body's energy reserves, result in obesity in mice and humans. However, the majority of obese humans do not have abno rmalities in leptin or its receptor but instead exhibit leptin resistance t hat could result from defects in downstream mediators of leptin action. Rec ently, two potential downstream mediators, agouti-related protein (Agrp) an d its receptor, the melanocortin-4 receptor (Mc4r), have been identified. A grp and Mc4r are excellent candidates for human disorders of body weight re gulation and represent promising targets for pharmacological intervention i n the treatment of these disorders.