Sir-The obese (ob) gene encodes a fat cell-derived blood-borne satiety factor (also known as leptin) that is involved in the regulation of energy homeostasis1-6. Mice homozygous for the ob mutation, ob/ob mice, develop severe hereditary obesity and non-insulin dependent diabetes mellitus1. The receptor for leptin (Ob-R), the dia-betes (db) gene product, is a single transmembrane protein closely related to the gpl30 signal-transduction component of class I cytokine receptors7. The receptor has several alternatively spliced isoforms (ae) 8• 9, which are expressed in a wide variety of tissues in a tissue-specific manner7-Ll. The longest isoform (Ob-Rb) is expressed at a high level in the hypothalamus, and is missing in db/db mice due to a mutation leading to its aberrant transcript8• 9. The rat gene fatty (fa) has been shown to be a homologue of the mouse db gene14• Recent studies have indicated that Zucker fatty (fa/fa) rats carry a missense mutation in the extracellular domain of Ob-R,