Why one enters torpor: focus on 'NPY Yl receptor antagonist prevents NPY-induced torpor-like hypothermia in cold-acclimated Siberian hamsters

摘要

neuropeptide y (npy) has long been known to play a major role in mediating energy balance. Intracerebral ventricular injection of NPY results in a vigorous feeding response and is perhaps the most orexigenic compound studied to date (3). NPY expression is robustly elevated within the hypothalamus of ca-lorically restricted animals, as well as in most genetic models of rodent obesity (i.e., ob/ob mouse and the Zucker fa/fa rat), and it is thought that this elevation is responsible for the ravenous appetite of these animals (20). NPY is coexpressed in neurons with another important modulator of feeding, agouti-related protein (AgRP) (14). These neurons reside alongside the anorexigenic proopiomelanocortin (POMC) neurons within the arcuate nucleus of the hypothalamus, where NPY/AgRP neurons inhibit activity of POMC neurons, but not vice versa (4). Importantly, ablation of the NPY/AgRP neuron in the adult mouse results in a lack of food intake with subsequent death from starvation (13). NPY-containing neurons send projections to various regions throughout the brain known to be involved with hunger, metabolism, growth, and endocrine function (14). When released at the synapse, NPY interacts with one of six flavors of NPY receptors, named Y1-Y6. The NPY Yl and Y5 receptors are the primary mediators for the feeding response to NPY or fasting (11). To date, most studies defining the orexigenic role of NPY have been performed in mouse and rat models. However, NPY's effects on food behavior can vary across species. For example, Siberian hamsters respond to both food deprivation and intracerebroventricular administration of NPY with only a moderate increase in food intake if food becomes available. Rather, the primary responses of these hamsters involve other behaviors associated with food, namely foraging and storage of food (1, 6). Hoarding and foraging appear to be mediated by the NPY Yl receptor, whereas hunger is mediated through the NPY Y5 receptor in the Siberian hamster (7).