AgRP in energy balance: Will the real AgRP please stand up?

The neuropeptide AgRP promotes food intake and weight gain by antagonizing signaling at melanocortin 3 and 4 receptors in the brain, but the limited phenotype of mice lacking AgRP raised questions about its importance. Four recent studies addressed this by creating mice in which AgRP neurons, which also express NPY and GABA, are ablated postnatally, and although details vary, they suggest that AgRP neurons are more essential to feeding and weight gain than is AgRP itself. A recent paper in Cell Metabolism (Wortley et al., 2005) indicates that AgRP itself is important for feeding and weight gain, but only as mice age, and the mechanism may involve dysfunction of the thyroid axis.