Individuals vary in their ability to control body weight. Obesity is frequently associated with insulin resistance and diabetes, both of which have reached epidemic proportions in many countries. The discovery of Douglas L Coleman led the way to the work of Jeffrey M Friedman, who uncovered a hormone that increased our understanding of the biological pathway that regulates body weight.
The studies began with the work of Coleman at the Jackson Laboratories in Bar Harbor, Maine. Coleman investigated two strains of mice (ob/ob and db/db), both of which exhibit grossly morbid obesity and severe diabetes, caused by homozygosity for two different recessive mutations. Coleman suspected that the ob/ob mice lacked a circulating hormone whereas the db/db mice overproduced it. So he joined the blood vessels of these two different mice in a technique called parabiosis. When joined to a db/db mouse, the ob/ob mouse stopped eating and lost weight, while the db/db mouse remained obese. Coleman concluded that the ob/ob mice failed to produce a hormone that inhibits eating whereas the db/db mice overproduced the hormone, but lack the receptor necessary to receive and transmit the hormone signal. When the circulations of ob/ob and db/db mice were joined during the parabiosis, the anti-obesity hormone from the db/db mouse crossed into the ob/ob mouse and induced its weight loss. The db/db mouse showed no change in body weight because it lacked the receptor.