From Our 2005 Archives

Appetite Suppressing Hormone Discovered

By Ed Edelson
HealthDay Reporter

THURSDAY, Nov. 10 (HealthDay News) -- There's a new entry in the field of weight-controlling hormones , a finding of potential importance to the millions of Americans trying to lose weight without giving up their zest for eating.

The Stanford University researchers who discovered it have named it obestatin. It acts to suppress appetite, and its commercial possibilities are noted by sponsorship of the research by the pharmaceutical company Johnson & Johnson.

Obestatin joins leptin, melanocortin and ghrelin, hormones identified in the last few years as acting on appetite and weight. So far, work with those molecules has not produced the hoped-for cure for obesity.

The obestatin discovery comes with a couple of twists. One is that it's produced by the same gene that produces ghrelin, which acts to suppress appetite. Another is that major credit for the discovery is given to Charles Darwin's theory of evolution.

The principles of evolution led to identification of obestatin, said Aaron Hsueh, a professor of obstetrics and gynecology at Stanford, in whose laboratory the work was done. He also credited the information gathered by the Human Genome Project, which produced a complete human gene map.

Hsueh and his colleges used human genome data to study small-peptide hormones, which are active throughout the body. Specifically, they looked at the receptors for those hormones -- the cellular molecules to which the hormones are attached when they go into action. There are about 300 such receptors, of which 100 had no known hormone partner.

The search for missing hormones was narrowed by focusing on receptors that have been around for hundreds of millions of years and are found in many species. One of those receptors is for ghrelin. Further studies showed that ghrelin actually had another protein tacked on to it -- obestatin.

When the researchers injected obestatin into rats, "to our surprise, we found that treatment with it suppresses food intake," Hsueh said. And so, he added, "it could have potential as an appetite-suppressing drug, by injection. Or it might be possible to deliver by nasal spray. It also allows us to screen for new drugs that might suppress appetite."

The study findings appear in the Nov. 11 issue of the journal Science.

But Matthias Tschop, associate professor of psychiatry at the University of Cincinnati, and co-author of an editorial in the journal on obestatin, is sounding a note of caution.

"The effect of obestatin on body weight seems to be relatively limited," Tschop said. "Also, it might cause some sort of illness or nausea that causes a decrease in food intake."

The effect of obsestatin was discovered in research with rodents, Tschop noted. "The most obvious question is, does obestatin work in obese animals?" he said.

And the business of weight regulation is complicated, Tschop added. "There are many other players involved," he said. "And obestatin may have many other functions. For example, it could regulate physical activity."

But with all those caveats taken into consideration, the discovery of obestatin is "a step in the right direction," Tschop said.

SOURCES: Aaron Hsueh, Ph.D, professor, obstetrics and gynecology, Stanford University, Palo Alto, Calif.; Matthias Tschop, Ph.D, associate professor, psychiatry, University of Cincinnati; Nov. 11, 2005, Science

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