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SCIENCE New finding in research on obesity shows single gene controls brain's food center


Published: Tue, September 13, 2005 @ 12:00 a.m.


When cells that produce the gene were destroyed, mice stopped eating.
LONG ISLAND NEWSDAY
A single gene controls "Food Central" in the brain, directing the day-to-day activity of a necessary human pastime: eating.
Now, Yale scientists have proved that the gene, AgRP, makes a protein that feeds brain cells that give orders about when to eat and how much. AgRP had been identified in earlier research as part of the brain pathway involved in appetite, but a range of genetic studies emerged empty-handed when the gene was deactivated early in development. Contrary to what scientists thought would happen, test animals kept eating.
But Tamas Horvath, chairman and associate professor at Yale School of Medicine, didn't give up on the gene, or the protein it makes. He designed a way to let the gene do its job and then wipe out the entire population of this kind of cell in one fell swoop in adulthood. Without the AgRP-producing brain cells, adult animals stopped eating. Completely.
"The only way to keep them alive was to force feed them through tubes," said Horvath, whose study appears in this week's issue of Nature Neuroscience.
These cells live and work in the hypothalamus, a region that orchestrates eating, sleeping and sexual appetite.
Horvath worked with Jens Bruening of the University of Cologne in Germany and half a dozen other scientists. They introduced an avian diphtheria toxin receptor into the AgRP neurons -- and separately into another population of brain cells thought to control satiety. These transplanted receptors had no effect on the brain cells. But when the mice were grown, two doses of the diphtheria toxin were injected into the animals. The toxin traveled to those specific receptors on the AgRP neurons, wiping out all the cells within 48 hours.
The mice stopped eating.


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