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# The discovery of leptin

## Problem

The existence of leptin, a 167 amino acid polypeptide hormone that functions to control appetite and feeding behavior, was hypothesized by D.L. Coleman in 1978, almost 20 years before advances in molecular biology allowed for the isolation of the hormone and the identification of its associated gene. Coleman derived his hypothesis from the interpretation of experiments he performed with mice harboring a genetic mutation called db. Mice with this mutation, called db/db mice, are obese, diabetic, and hyperphagic (exhibit uncontrolled eating). When Coleman connected the circulatory system of a lean mouse with the circulatory system of a db/db mouse (referred to as “parabiosis”), the lean mouse eventually died of starvation, while the db/db mouse lived on, unaffected. In order to explain this result, Coleman hypothesized that the db/db mice produce a circulating molecule that, when introduced to the lean mouse via parabiosis, causes the lean mouse to cease eating, eventually leading to death by starvation. Subsequent research confirmed Coleman’s hypothesis: db/db mice produce abnormally large quantities of leptin, and the introduction of these large quantities of hormone to the circulatory system of lean mice precipitates their starvation and eventual death.
In addition to his studies with the db mutation, Coleman also studied mice with a different genetic mutation, occurring on a different chromosome, called ob. Mice with this mutation, called ob/ob mice, are obese, diabetic, and hyperphagic, just like db/db mice. The following table contrasts the results of parabiosis experiments involving db/db mice, lean mice, and ob/ob mice.
Table 1. Results of three parabiosis experiments: db/db with lean, db/db with ob/ob, and lean with ob/ob.
Experiment onedb/db: no change observedLean: hypophagia, hypoinsulinemia, and hypoglycemia. Death by starvation.
Experiment twodb/db: no change observedob/ob: hypophagia, hypoinsulinemia, hypoglycemia, and reduction in adipose tissue mass. Death by starvation
Experiment threeLean: no change observedob/ob: normalization of eating behavior, blood glucose levels, and circulating insulin levels. Reduction in adipose tissue mass.
How many nucleotides long is the gene that codes for the hormone leptin?