Anti-fat pill could help keep the Weight Off

Nov. 27, 2008— -- 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."

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.

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.