Leptin and the brain: then and now

The discovery of the adipocyte hormone leptin and the demonstration that severe obesity in ob/ob and db/db mice results from mutation of genes encoding leptin and its receptor, respectively, ushered in a new era of obesity research. Our investigation into mechanisms mediating CNS actions of insulin led us to ask whether the two hormones act on a common set of hypothalamic targets. Our finding that this is indeed the case prompted studies that continue to this day. While substantial progress has been made in understanding brain mechanisms of leptin action, translating this knowledge into more effective treatment of obesity remains an elusive goal.