Featured Review Cellscience Reviews Vol 4 No 1 ISSN 1742-8130

The Role of the Agouti-Related Protein in Human Energy Balance Regulation

The Agouti-Related Protein (AgRP) is a powerful orexigenic peptide that increases food intake when ubiquitously overexpressed or when administered centrally. AgRP-deficiency, on the other hand, leads to increased metabolic rate and a longer lifespan when mice consume a high fat diet. In humans, AgRP polymorphisms have been consistently associated with resistance to fatness in blacks and whites and resistance to the development of type-2 diabetes in African Blacks. What remains to be seen is whether polymorphisms could also predispose humans to a longer lifespan under obesigenic (or even lean) conditions. AgRP may be envisioned as a molecule that when overexpressed could have undesirable effects on human physiology but when underexpressed, or if the protein is defective due to mutations, could result in improved metabolic fitness and perhaps lead to an extended lifespan for individuals consuming obesigenic diets. New studies will need to investigate the possibility that AgRP lies at the crossroads of energy balance regulation and healthy aging.

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