Timelines: 1994
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Leptin
A molecular understanding of obesity
Biomedical researchers Rudolf L. Leibel and Jeffrey M. Friedman announce that they have identified and sequenced the gene that codes for the hormone leptin in work conducted with obese mice at Rockefeller University in New York City. Leptin is produced (mainly, but not exclusively) by adipocytes, fat cells. Levels of the hormone circulating in the blood are directly proportional to percentage of body fat. Leptin is involved in appetite regulation. It signals satiety to the brain (by binding to and reducing the activity of certain neuropeptides). Individuals with homozygous mutations in the leptin gene do not generate these signals, remain perpetually hunger, and typically suffer from severe obesity.
The effects of the hormone were first observed in obese, ravenous mice at the Jackson Laboratory in Bar Harbor, Maine, in 1950. Several strains of mice that display these characteristics – ‘ob/ob’ mutants – have been bred for medical and genetics research. Researchers have found that when treated with injections of leptin, ‘ob/ob’ mice shed fat and tend toward renormalized body weights. The result makes leptin therapies for human obesity a tantalizing prospect, but experimental treatments with recombinant versions of the hormone have been disappointing – in contrast to the dramatic effects observed in mice, only mild metabolic responses have been generated in human beings, and only at very high doses. Research on the biological functions of the hormone continues.
