Scientists Report Finding Weight-Control Receptors : Research: Molecular ‘antenna’ conveys message from protein telling the body to stop eating. Its discovery may lead to treatments for obesity.
Only six months after scientists discovered a protein in blood that tells the body when to stop eating, a competing research team has found the molecular “antenna” that receives that message and passes it on to fat-burning and appetite-control centers.
The discovery, achieved after a furious search through hundreds of candidate molecules, is expected to speed development of new treatments for obesity.
The newfound antennas, known as leptin receptors, are convoluted proteins that stud the outer surface of brain cells and perhaps other cells in the body. Scientists believe that when these receptors detect leptin, the body’s recently discovered “fullness signal,” they pass a “stop eating” message to relevant parts of the brain. A series of discoveries in the past few months has suggested that obesity is often caused by a defect in this receptor--or in the still-unidentified relay stations to which the receptor passes its message.
Scientists said that, with the leptin receptor in hand, it should be relatively easy to identify those second- and third-tier relay stations, revealing for the first time the molecular chain of events that regulates appetite and energy metabolism. Ultimately, they hope to find drugs that act specifically on those mechanisms.
“How things will turn out in the end is difficult to predict but I’m very optimistic,” said Louis A. Tartaglia, a scientist at Millennium Pharmaceuticals in Cambridge, Mass., who led the search. “The goal will be to tickle the receptor.”
Tartaglia reported the work in today’s issue of the journal Cell, along with Robert I. Tepper and others from Millennium and scientists from Hoffman-La Roche, the Swiss pharmaceutical company. Indicative of the intense interest in the receptor, Cell published the results only three weeks after receiving the manuscript. It typically takes several months for scientific journals to publish reports.
The work builds on research by Rockefeller University scientist Jeffrey Friedman, who last July announced the discovery of a weight-controlling protein called leptin, made by fat cells. As fat stores build up, fat cells release more leptin, suppressing appetite and adjusting metabolic rates to maintain the body’s normal weight.
Scientists at first hypothesized that many cases of obesity could be caused by insufficient leptin supplies or mutated versions of leptin that do not function properly. Amgen, a biotechnology company based in Thousand Oaks, Calif., quickly paid the Friedman team $20 million for the rights to make a diet pill based on leptin. But recent work has indicated that fat people make plenty of leptin; their bodies just do not listen to leptin’s message. Thus began the race to map the leptin receptor system.
Tartaglia and his colleagues first found the leptin receptor in mice. To their surprise, they found evidence of leptin receptors in many tissues, including the kidney and the lung. But the mother lode was in the choroid plexus, a layer of tissue lining the fluid-filled chambers, or ventricles, of the brain.
