Grant: Operating Grant

Obesity and eating disorders represent an enormous problem in western society, with obvious cost to both individual health and the health care system. Despite intensive investigation and steady advances in our knowledge about the ways in which appetite and eating work, we still do not have a complete picture of how the brain controls these behaviours. Further new insights are necessary to combat this escalating health problem. We have recently discovered that mice lacking the gene for the specialized calcium transport protein known as the K+-dependent Na+/Ca2+-exchanger type 4 or NCKX4 for short, are healthy but weigh 30% less than normal mice because they eat about 30% less food. Although various hormones and brain circuits have previously been suggested to control feeding behavour, this is the first time that a membrane calcium transport protein has been shown to have an effect on eating behaviour. Our discovery creates a whole new opportunity both to understand the way eating is normally controlled, and to study an unexpected target for the development of new treatments for eating disorders and obesity. The experiments proposed here will lead to an in depth understanding of where and how the NCKX4 protein works in brain nerve pathways that control feeding behaviour and satiety. This information will be critical in understanding normal feeding behaviour and the events that underlie its dys-regulation, possibly leading toward the development of novel therapeutic agents for eating disorders.