Scientists claim to have found a 'fullness' hormone that could help fight the obesity epidemic.
When volunteers received a dose of the hormone, called PYY3-36, they helped themselves to one-third less food from a free buffet, and ate less for up to 12 hours.
Professor Stephen Bloom of Imperial College, London, and his colleagues propose in the current issue of Nature that PYY3-36 travels to the brain's hypothalamus, where it shuts down nerves that trigger eating.
"It's what stops you having the third helping," said Professor Bloom.
In the latest studies, 12 healthy non-obese men and women fasted, then were infused with either PYY3-36 or saline for 90 minutes. Neither the patients nor the researchers administering the treatment knew who was receiving which treatment.
The dose of PYY3-36 mimicked the level seen in the blood after a normal meal.
Significantly, calorie intake during a free-choice buffet meal two hours after the infusion was reduced by more than a third compared with the saline controls.
Not only that, analysis of food diaries showed a significant inhibition of food intake in the 12-hour period after the hormone infusion.
In 1984, the group published the first human studies to show that PYY3-36 infusions slowed down the rate at which the stomach empties. These also showed that PYY3-36 is made in the endocrine cells of the intestine and is released into the bloodstream when food is eaten.
Their new research shows that PYY3-36 in the circulation penetrates and switches off only that part of the brain that regulates appetite.
In other words, it appears to reduce food intake by activating the neuropeptide Y Y2 receptor, an effect that inhibits neuropeptide Y-producing neurons in an area in the hypothalamus called the arcuate nucleus.
Neuropeptide Y is a very potent stimulator of appetite, so inhibiting these neurons means you eat less.
The researchers hope drugs mimicking PYY3-36 taken before mealtime could curb appetite and help fight weight gain.
"Obviously one could use the peptide itself, although that might be too expensive in the long run," said Professor Herbert Herzog, from Sydney's Garvan Institute of Medical Research. His research group generated and tested a strain of mice deficient in the Y2 receptor. As a result, the hormone's action is no longer detectable.
As for developing synthetic compounds, Professor Herzog is optimistic, not least because the problem with many drugs, of reaching hidden sites within the brain, does not apply.
"The Y2 receptor responsible for this action sits outside the so-called brain barrier and is easily accessible by compounds in the blood," he said.