E-00491-2002-R1 NPY Ablation in C57BL/6 Mice Leads to Mild Obesity and to an Impaired Refeeding Response to Fasting Running Title: NPY Ablation Impairs Refeeding after a Fast

Neuropeptide Y (NPY) is an orexigenic (appetite-stimulating) peptide that plays an important role in regulating energy balance. When administered directly into the central nervous system, animals exhibit an immediate increase in feeding behavior while repetitive injections or chronic infusions lead to obesity. Surprisingly, initial studies of Npy -/mice on a mixed genetic background did not reveal deficits in energy balance, with the exception of an attenuation in obesity seen in ob/ob mice in which the NPY gene was also deleted. Here, we show that on a C57BL/6 background, NPY ablation is associated with an increase in body weight and adiposity, and a significant defect in refeeding after a fast. This impaired refeeding response in Npy -/mice resulted in a deficit in weight gain in these animals after 24 hours of refeeding. These data indicate that genetic background must be taken into account when evaluating the biological role of NPY. When examined on a C57BL/6 background, NPY is important for the normal refeeding response after starvation and its absence promotes mild obesity.