Conditional deletion of neurogenin-3 using Nkx2.1iCre results in a mouse model for the central control of feeding, activity and obesity

A number of interconnected hypothalamic nuclei are involved in the central control of energy balance. These include the arcuate nucleus (ARC), ventromedial hypothalamic nucleus (VMH), lateral hypothalamic area (LH), dorsomedial hypothalamic nucleus (DMH) and periventricular hypothalamic nucleus (PVN). The ARC and VMH are exposed to the circulation owing to active transport of metabolic signals such as leptin, glucose and insulin across the blood-brain barrier. These signals are then detected in the ARC and VMH due to the presence of transmembrane receptors. Within the ARC, there exists two related but exclusive neuronal populations regulating energy balance: the neurons expressing proopiomelanocortin (Pomc) and cocaine- and amphetamineregulated transcript (Cart), and those expressing neuropeptide Y (Npy) and agouti related peptide (Agrp). Pomc/Cart neurons are located within the lateral domain of the ARC and act to inhibit feeding activity, whereas Npy/Agrp neurons are expressed more medially, and act to promote feeding. Pomc/Cart neurons are a heterogeneous population, with distinct subpopulations capable of responding to different signals, such as leptin via the leptin receptor (LepR), glucose via glucose-sensitive potassium (K + ) channels such as Sur1 and Kir6.2, and insulin (Cowley et al., 2001; Ibrahim et al.,