How to unleash an appetite suppressant

First isolated by the late Aaron B. Lerner, M.D., Ph.D., a renowned Yale researcher and dermatologist, α-melanocyte-stimulating hormone, or α-MSH, is a pituitary hormone with a variety of effects. In the skin and hair, α-MSH stimulates the release of melanin, causing dark pigmentation; in the brain, the hormone acts as a powerful, but short-lived, appetite suppressant.

To discern why α-MSH is deactivated so rapidly, a group led by Sabrina Diano, Ph.D., associate professor of obstetrics, gynecology, and reproductive sciences and of neurobiology, examined two closely related mouse strains, one fat and one lean.

As Diano and her colleagues report in the July 20 issue of The Journal of Clinical Investigation, the leaner mice lacked a gene that codes for an enzyme known as PRCP. The team then demonstrated that PRCP blunts α-MSH’s action by knocking off a single amino acid. Moreover, the group showed that PRCP is abundant in nerve cells of the hypothalamus, a brain region known to govern eating behavior.

“Our findings provide a possible new target for the development of drugs to control metabolic disorders such as obesity and type 2 diabetes,” says Diano.