ARTICLE | Targets & Mechanisms

Curbing Mitochondrial Appetite

August 28, 2008 7:00 AM UTC

Several companies have tried and failed to develop obesity drugs that agonize mitochondrial uncoupling proteins, which let adipose cells generate heat by burning excess fat. A new study now suggests that one member of this protein family, uncoupling protein 2 (mitochondrial, proton carrier), plays a different role in the brain-scavenging reactive oxygen species-and should actually be antagonized to suppress appetite.1 Although companies and academics think blocking this protein may be easier than agonizing it, the challenge of getting compounds into the brain and mitochondria remains formidable.

A team from Yale University, led by Tamas Horvath, professor of comparative medicine, neurobiology, obstetrics and gynecology,and Sabrina Diano, assistant professor of obstetrics and gynecology, reported in Naturethat uncoupling protein 2 (mitochondrial, proton carrier) (UCP2) sits downstream of a hotly pursued metabolic target in the obesity space: ghrelin...