When administered to ob/ob mice or human patients with a mutation in the leptin gene, leptin lowers blood glucose levels and resensitizes cells to insulin.
In the ob/ob mice, a mutation in the leptin gene causes leptin deficiency and decreased interaction between leptin and its receptor; therefore, the ob/ob mice are hyperphagic, extremely obese, and inactive [ 26].
Conversely, db/db mice, which express leptin but have a mutation in the leptin receptor, displayed small tumors, suggesting that leptin has a tumor-suppressive role [ 95].
Due to excessive weight gain beginning at age 3 months, and to familial history of leptin deficiency caused by a mutation in the leptin gene, that gene was genotyped when he was 2 years old.
53, 54 Moreover, a morbidly obese child who was found to have a mutation in the leptin gene was successfully treated with recombinant human leptin.
Since the late 1990s, there's been enormous interest in harnessing leptin as a weight-loss drug, but so far, it's proven most effective for a small number of people who have a mutation in the leptin receptor gene.
In a remote Turkish village, researchers have located a family with a mutation in the leptin gene similar to the one found in lab mice, and--just like the mice--adults with two copies of the mutation are grossly overweight and don't ever go through puberty.
To do this, we utilized OB/OB knockout mice, in which a mutation in the leptin gene results in profound obesity[31].
A well-established murine model is the C57BL/KLS-leprdb/leprdb (db/db) mouse that has a mutation in the leptin receptor.
This has been applied to environmental biomes [10] as well as the gastrointestinal microbiomes of C57BL/6J mice with or without a mutation in the leptin gene [11], and was recently used to analyze ∼14 million pyrosequences from 45 distinct microbiomes and 42 viromes [12], including the ones analyzed in detail in this study.
A mutation in the leptin receptor has previously been reported to cause obesity in humans [ 29].
