Sooner or later during a meal–unfortunately often later–you become satiated, and your body lets your brain know that there’s no need to eat more. Scientists suspect that the body coveys this message in multiple ways, but one research team now reports that a hormone discovered more than 2 decades ago could be the primary satiety signal sent to the brain.
People who fasted and then received an injection of the hormone, called PYY3-36, 2 hours before an open buffet ate about one-third less than when they didn’t get the hormone. And young mice receiving twice-daily injections of the hormone over a week showed suppressed appetites and far less weight gain than untreated rodents did.
These and other findings reported in the Aug. 8 Nature suggest that studies of PYY3-36 could lead to new ways of treating obesity and eating disorders. “It’s a pretty potent appetite inhibitor,” says Stephen R. Bloom of Imperial College in London, who led the work.
In many ways, PYY3-36 appears to be the counterpart of ghrelin, a stomach-produced hormone that travels to the brain and stimulates appetite (SN: 2/16/02, p. 107: The Hunger Hormone?). The concentration of ghrelin in a person’s blood rises before meals and falls afterward, whereas PYY3-36 follows the opposite pattern. Instead of directly blocking ghrelin’s hunger-inducing actions, physicians might use PYY3-36 or mimics of it to curb appetite.
Ghrelin and PYY3-36 “are roughly equally potent. One increases food intake by about a third; the other decreases it by about the same amount,” says Bloom.
In the 1970s, scientists found PYY3-36 in pig intestines. Bloom and other investigators subsequently discovered that the small and large intestines of people secrete PYY3-36 into the blood after every meal in amounts proportional to the caloric content of a meal. In the 1980s, the researchers injected the protein into people to study its effects on stomach actions such as acid secretion.
“We didn’t think to look at appetite,” says Bloom.
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In the new work, the researchers found that the hormone prevents specific brain cells from secreting a potent appetite-inducing chemical signal. They also identified the brain-cell-surface protein that PYY3-36 acts upon, a potential target for drugs mimicking the gut hormone. Scientists will probably seek an oral drug, since PYY3-36 must be administered by injection.
To reveal all the hormone’s roles, Bloom’s team is creating genetically engineered mice that lack PYY3-36. “It seems to be a postdigestive hormone, switching off appetite, delaying the emptying of the stomach because enough food has gotten into the intestines, and inhibiting acid secretion because you finished eating and no longer need it,” he says.
The range of findings that Bloom and his colleagues present impresses David E. Cummings of the University of Washington in Seattle, who studies ghrelin. In a single report, he says, they’ve shown appetite suppression by the hormone in both rodents and people and described the brain pathway by which PYY3-36 appears to work.
Still, Cummings notes that other putative satiety factors have generated excitement but failed to develop into a viable drug for obesity. “We’ve been down this road before,” he cautions.