Here's the skinny

(A tip of the hat to Darwin)

Calef Brown


When scientists discovered the hormone ghrelin a few years ago, they thought they had found the last of the major genes that regulate weight. They were wrong.

Introducing obestatin, a newly discovered hormone that suppresses appetite.

The finding, published in the Nov. 11, 2005, issue of Science, offers a key to researchers developing treatments for obesity. In a nation that desperately needs to slim down — the U.S. Centers for Disease Control and Prevention estimates 65 percent of Americans over the age of 20 are either overweight or obese — obestatin is generating interest from scientists and drugmakers alike.

Professor Aaron Hsueh, PhD, uncovered obestatin by using the principles of evolution to pick clues from data held in the Human Genome Project, as well as the genome sequencing projects for many other organisms, including yeast, fruit flies and mice.

“Darwin led us to this new hormone,” says endocrinologist Hsueh, who oversaw the research. The project, conducted in his lab and sponsored by Johnson & Johnson Pharmaceutical Research & Development, shows the great value of genomic databases, says Hsueh. In less than a year, the small team of seven scientists used them to zero in on this previously unknown but vitally important hormone.

The new finding could clear up some confusion over how appetite-regulation hormones work. Since the ghrelin protein increases appetite, scientists had expected that experiments deleting the protein’s gene would turn appetite off. So when deleting the gene had almost no effect on growth or appetite, they were perplexed.

Now they have a possible explanation. Hsueh’s finding shows that deleting the gene for ghrelin also takes out obestatin — because ghrelin and obestatin are encoded by the same gene.

It’s rare for more than one protein to come from a single gene sequence. What makes this case even more unusual is that two proteins from the same sequence have such opposite effects: Obestatin behaves in some ways as the “anti-ghrelin.”

“That was a big surprise,” says Hsueh.

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