- 17:00 26 November 2008 by Ewen Callaway
A pill might replace that third helping of turkey at future Thanksgiving and Christmas dinners. A newly-discovered chemical found naturally in our body blocks hunger and weight gain.
Mice and rats - and presumably humans - produce the chemical after eating a fatty meal. When researchers gave the rodents an extra dose, they ate less and shed weight, with no ill effects.
If similar tests in larger animals pan out, humans will be next, says Gerald Shulman, a molecular biologist at Yale University in New Haven, Connecticut whose team discovered this new role for the molecule, called
N-acylphosphatidylethanolamine (NAPE).
"We have this epidemic of obesity and we have very few agents that are able to effectively treat obesity," he says. "We'd be quite interested in trying a clinical trial to see if giving this back would reduce food intake in humans."
More, gimme more
Fatty foods, be they milkshake, French fry or Big Mac, have long confounded researchers seeking to explain how our body determines when it has had enough. Levels of fatty acids - the building blocks of junk foods - actually fall when people gorge on greasy foods, only to increase with hunger.
This peculiar behaviour prompted Shulman, Yale biologist Matthew Gillum and their colleagues to scour blood for compounds that shot up after a fatty meal.
NAPE fit the bill. Fatty acids in food get converted to NAPE in the gut before heading to the bloodstream.
From there, the chemical races into the brain's appetite centre, in the hypothalamus, and shuts down neurons involved in signalling hunger,Shulman's team found.
Post-prandial nap
This explains why mice and rats injected with natural levels of NAPE act like they've gorged. They show little interest in stuffing their faces, and the normally athletic animals give in to languor.
"It's kind of like a siesta response. After an animal eats a heavy meal, it wants to sit in the corner and nap," Shulman says.
After five days on NAPE, rats ate 30% less food and lost a quarter of their weight.Rodents that didn't get NAPE actually gained a little flab. Shulman's team didn't notice any other permanent behavioural changes in the NAPE-fed mice.
Problems controlling production of the chemical could underlie diseases like obesity and diabetes, Shulman suggests.
When their mice gorged on fatty foods for more than a month, NAPE levels in their blood no longer waxed and waned with each meal, but extra NAPE still suppressed their appetites.
Obesity pill?
It's too early to tell whether giving humans NAPE will offer the same benefits. Humans produce the molecules, and Shulman's team is now working to determine how they track with fatty food intake.
"I think they made a good case that [NAPE] should be considered among the factors the body uses to regulate food intake," says Michael Schwartz, an endocrinologist at the University of Washington in Seattle. "It does raise the possibility that this could be a new approach to treatment, but we know really little."
The molecular intricacies of NAPE's appetite-sapping effects have yet to be ironed out, and problems could emerge if the chemical does more than curb appetite. "It's hard to target the brain in a way that doesn't have side effects," says Schwartz.
Matthias Tschöp, an obesity researcher at the University of Cincinnati, says understanding how NAPE affects our appetite for fat would hopefully lead to new drugs that muzzle hunger, without eliminating it.
Journal reference: Cell (DOI: 10.1016/j.cell.2008.10.043)
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