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Scientists Find Hunger Hormone

February 19, 1998

BOSTON (AP) _ Scientists believe they have found the brain’s hunger hormone, the stuff that triggers the overwhelming urge to say, ``Another helping of mashed potatoes, please. And lots of gravy!″

The discovery is likely to start a stampede of research intended to find medicines that can rein in this substance and help people say no to food.

The researchers were led by Dr. Masashi Yanagisawa of Howard Hughes Medical Institute at the University of Texas Southwestern Medical Center. They are reporting the finding in Friday’s issue of the journal Cell.

The scientists called their discovery ``orexin,″ a play on ``orexis,″ the Greek word for hunger.

``We believe that orexin is one of the important pathways in the regulation of hunger,″ said Yanagisawa.

The researchers found that two varieties of orexin are made by nerve cells in the lateral hypothalamus, a part of the brain already known to play a role in appetite.

``It’s an absolutely beautiful piece of work,″ said Dr. Jeffrey Friedman of Rockefeller University, ``a very thorough and technically elegant set of studies that identify two new players in the system that controls weight.″

The work suggests that the brain churns out orexin when it senses a need to eat, such as after a drop in sugar levels in the blood.

The same substance appears to be at work in rats as well as probably many other creatures. This allows the scientists to test its effects.

They gave orexin to lab rats and found it made them ravenous. For an hour or two, they ate eight to 10 times more food than they ordinarily would.

They also checked the brains of rats that had not eaten in a day and found that their orexin levels had gone up.

``It really makes a nice feedback loop to regulate your appetite,″ said Yanagisawa.

He said the possibility of harnessing this discovery to combat eating problems _ both lack of appetite and its far more common opposite _ are already being investigated by scientists at SmithKline Beecham Pharmaceuticals, which collaborated on the discovery.

He said it should be possible to create drugs that mimic orexin and make people eat more. This could be helpful for cancer patients and others who have illnesses that rob their appetites.

Even more important, perhaps, would be using this discovery to make drugs for treating obesity. The scientists know the exact spot on the surface of cells in the brain where orexin does its business. So it should also be possible to create medicines that block these spots, called receptors, so orexin cannot get in and trigger the munchies.

The scientists believe many hormones besides orexin are involved in both creating and suppressing appetite.

One of these is leptin, an appetite-suppressing protein made by fat-filled adipose cells. While leptin is supposed to signal the brain to stop eating, the signal somehow does not get through properly in overweight people.

Yanagisawa said that leptin _ or the lack of it _ could be one of the signals that triggers the brain to make orexin and whet the appetite.

The discovery was made through a relatively new process called reverse endocrinology.

Traditionally, scientists discover a hormone and then try to figure out what it does by searching for the receptor that it attaches to. In this case, however, the scientists discovered the receptor but had no idea what hormone acted on it or what it did.

Working with the receptor, they figured out which protein fit into it. Still, they did not know at first that it was involved in appetite. Their first clue was the discovery that the protein was a hormone made by particular nerve cells in the hippocampus.

``As soon as we saw the striking distribution of these neurons in that part of the brain, we guessed these hormones were doing something important in determining how much you eat,″ he said.

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