The first hint that obesity has a genetic rather than a totally behavioral basis came in 1994 when Rockefeller University researchers identified the obese gene and cloned the murine version of it.3 The mice were obese, suffered from Type 2 diabetes, and lacked the protein leptin which appears to act primarily on the hypothalamus, where it influences appetite and energy use. The discovery opened the genetic floodgates. "[It] was the paradigm shift that turned [obesity] into a tractable problem," remarks clinical endocrinologist Stephen O'Rahilly, University of Cambridge, who studies the genetics of childhood obesity. O'Rahilly's research had focused on severe insulin resistance in children; after the discovery, he shifted to investigating leptin deficiency in extremely obese youngsters and their families.
"Among the first kids we looked at, we did find a pair of first cousins who were [leptin] deficient," says O'Rahilly. In total, they found three families with this deficit; ...
