Historical Tidbit: Then and Now: This Month in Endocrine History
Submitted by Evan Graber, DO
In July 1995, Dr, Halaas and colleagues reported on a molecule that decreased murine food intake, energy expenditure, and weight. Mice homozygous for deletions in the obese gene (ob/ob) were used as models of human obesity. The ob gene was cloned and transfected into E. coli resulting in OB protein that could be purified and injected into 3 groups of mice: ob/ob, wild type, and db/db mice who were also obese and were previously shown to have very high levels of OB protein consistent with OB protein resistance. The ob/ob mice lost ~40% body weight in 33 days and food intake dropped below that of the wild type mice. There was no significant decrease in weight or food intake in the db/db mice. Human OB protein was also isolated and injected in the ob/ob mice, with similar effect to the mouse OB protein implying a possible role of OB protein use in weight loss for humans.
Now we know the OB protein better as leptin, a name first proposed by the study group and coming from the Greek leptós, meaning thin. We know leptin is secreted by adipose tissue and is amongst several molecules involved in food intake and energy expenditure regulation. Patients with leptin deficiency or resistance display obesity, hyrerphagia, and hypogonadotropic hypogonadism. This last feature highlights the role leptin has in regulating pubertal onset via it’s interaction with kisspeptin neurons in the hypothalamus.