Obesity, a common nutritional disorder, is associated with diabetes, hypertension, hyperlipidemia, cancer and many other health related problems. At least five genes, Obese (ob), diabetes (db), fat (fat), agouti yellow (Ay), and tubby (tub) have been linked to obesity. Recently, Ob genes (mouse and human) have been cloned. Obese gene encodes an adipocyte-tissue derived secreted Ob protein/Leptin (167aa, ~16kD) that controls body weight homeostasis. Exogenous administration of recombinant Ob protein can reduce food intake and body weight. However, Ob protein had no effect in db/db mice suggesting a defect in leptin signaling mechanism. Leptin exert its effects by interacting with leptin receptors (obese receptors). The Ob-R has been shown to be a product of db gene that has long been thought to encode the receptor for a weight-controlling hormone. The Ob-R has at least 6 alternatively spliced forms with modifications at the amino and C-terminus.