Key Words

Food intake and energy metabolism are regulated by a complex interplay between neural networks in the cen-tral nervous system and peripheral tissues. Within the central nervous system, food intake is largely controlled by a fine balance between orexigenic and anorexigenic neuropeptides in the arcuate nucleus (ARC) of the hypo-thalamus. Neuropeptide Y (NPY) and agouti-related pro-tein (AgRP) are coexpressed in neurons of the ARC and are potent orexigenic peptides, whereas pro-opiomelano-cortin (POMC) precursor protein in the ARC is cleaved into anorexigenic -melanocyte-stimulating hormone ( MSH) peptides. NPY/AgRP and POMC neurons in the ARC are arguably considered ‘first-order ’ sensory neu-rons in the control of food intake. These neurons receive, coordinate and respond to changes in varying humoral factors, such as hormones, glucose and fatty acids, associ-ated with different metabolic states. Both NPY/AgRP and POMC neurons project to the paraventricular nucleus (PVN) (see fig. 1). The critical importance of both NPY/AgRP and POMC neurons in food intake and energy balance is highlighted by elegant conditional gene deletion experi-ments. Conditional deletion of AgRP neurons in the ARC was achieved by targeting the human diphtheria toxin to the AgRP locus. Adult mice were subsequently treated with diphtheria toxin to destroy AgRP neurons