Agouti and Agouti-related Protein: Analogies and Contrasts

The discovery a decade ago of the murine agouti gene was intended to bring scientists a step closer to understanding the complexities of mammalian pigmentation. The first obesity gene was also uncovered in the process. What followed was an explosion of major discoveries in murine as well as human obesity and diabetes research. Recently, a new gene, the agouti-related protein (AGRP), 1 was discovered and found to share a striking similarity in structure and function with agouti, although their patterns of distribution are completely different. Identification of a hypothalamic melanocortin receptor, MC4-R, together with AGRP as central components of feeding behavior and metabolism has helped build a picture, albeit incomplete, of the neuronal pathways involved in energy homeostasis. This review will compare and contrast Agouti and AGRP structure and function and gene regulation and their interaction with melanocortin receptors (MC1-R and MC4-R) and suppressors (mahogany/mahoganoid).