The present invention relates to a variant from of the receptor for the obese gene product. In particular, the invention relates to methods of detecting this receptor variant in cells and tissues of obese individuals. In addition, it relates to methods of inhibiting or down regulating expression of this variant in cells to augment their responsiveness to weight regulation by leptin as well as methods of using compounds to directly activate signal transduction pathways associated with this ligand-receptor system. In addition, the invention relates to identifying compounds capable of supplementing biological activity of leptin on cells expressing a leptin receptor variant.