Gene identified as key to our eating habits

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. ‘‘Until now, there was no experimental evidence to prove that AgRP neurons regulate eating behavior.’’ 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.

In addition, they experienced a drop in blood glucose, plasma insulin, and a dip in the hormone leptin also associated with feeding behavior. ‘‘This is not the only regulator of feeding,’’ the scientist said. ‘‘But when these cells are knocked out, little else matters. Without food, these animals would die.’’

He added ‘‘that it’s now reasonable to target this protein when developing treatment.’’ Horvath said any obesity drug that would work to stop eating would be a blockbuster. ‘‘There is no Viagra for metabolic obesity,’’ he said.

And he suspects the technology could be used to study many other diseases by wiping out specific populations of cells at any stage in the lifespan.

LAT-WP