The Secret of Feeling Full

In essence, researchers are discovering, the digestive system tells the brain how much to eat by pumping various hormones, one of which is PYY, into the bloodstream. "There are at least half a dozen signals that we know about," says Michael Cowley, a neuroscientist at the Oregon National Primate Center in Beaverton and one of the co-authors of the Nature paper. Some of these biological traffic lights work in a very short time frame, affecting when you start and stop a meal. Some, like leptin, work over the longer term by helping the brain monitor how much fatty tissue the body has stored. PYY is a medium-term signal; it seems to suppress your appetite between meals, presumably so you can get some work done before you start eating again. What complicates things is that these signals are interconnected; if the level of one hormone falls or rises long enough, the whole system will shift until the hormones fall back to their original levels.

You know exactly what that feels like if you have ever tried to lose weight and then hit a plateau after a while. What is happening is that the changes in your digestive hormones have signaled the brain to lower your metabolic rate so that your body makes more efficient use of the calories you consume. Your appetite increases, and any further weight loss takes just that much more effort and determination.

What gets neuroscientists excited is that most of these digestive hormones seem to affect the same group of neurons in the hypothalamus, a subsection of the brain that acts as a kind of master regulator of some of our more basic instincts--hunger, thirst, sleep, sex. That means if PYY fails to be a good candidate for a new antiobesity drug, researchers may find another target in the brain that works better. Alternatively, studying PYY may help with the opposite problem--loss of appetite--which so often affects cancer patients and people with AIDS.

Either way, a lot of work remains to be done. The 12 volunteers tested by Bloom and his colleagues were all healthy and of average weight. Perhaps the same biological factors that kept their weight under control also enabled them to respond to PYY. Bloom is already trying the hormone on two more groups of volunteers--one modestly overweight and the other slightly underweight--to see if the hormone will suppress their appetites as well. "We also want to move to long-term treatment and prove that over a week, say, you're still eating less," Bloom says. He is looking into the possibility that certain foods, particularly those high in fiber, may increase the level of PYY in the body naturally.

One thing seems pretty clear: any future medical treatment of obesity will probably require a combination of drugs. Imagine for a moment, says Dr. Michael Schwartz, an endocrinologist at the University of Washington in Seattle, that scientists figure out a way to turn PYY into an easy-to-swallow pill, that the pill turns out to work for a wide range of people and that those who take it begin losing weight and shed, say, 5% to 8% of their body weight. At that point, some of the other hormones that affect long-term weight control, such as leptin and insulin, start dropping, and a short-acting hormone called ghrelin starts climbing, increasing your sense of hunger. "Now your body is competing with the effect of the drug," Schwartz says. "In the end, you may need two or three drugs to get the desired effect."