Gut chemical may inspire new way to fight obesity

WASHINGTON Wed Nov 26, 2008 3:29pm EST

A passenger waits for a flight at Heathrow airport in London August 12, 2006. REUTERS/Toby Melville

A passenger waits for a flight at Heathrow airport in London August 12, 2006.

Credit: Reuters/Toby Melville

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WASHINGTON (Reuters) - Scientists have identified a fatty substance made in the gut that signals the brain when it's time to stop eating -- a discovery that could inspire new approaches to fighting obesity.

Writing in the journal Cell on Wednesday, U.S. researchers said experiments with mice and rats showed that a naturally occurring fat-derived chemical messenger called NAPE regulated how much the animals ate. It is present in people and may do the same thing, they said.

Gerald Shulman of Yale University and the Howard Hughes Medical Institute and colleagues said that when the rodents were fed a fatty meal, their small intestine made a lot of NAPE and put it into the bloodstream. It then traveled to the brain and shut down hunger signals, they said.

NAPE levels shot up after the rodents ate a fatty meal, but not when they ate only protein or carbohydrates, they said.

The researchers then synthesized NAPE and injected it into the abdomen of the animals, whose appetites diminished greatly. When NAPE was delivered in much smaller amounts directly to the brain, it had the same effect on appetite as a larger dose injected into the bloodstream.

NAPE concentrated in the hypothalamus, an important brain structure known to regulate hunger, and inhibited neurons that stimulate appetite, they said.

When the rodents were given extra NAPE for five days, they animals ate less and lost weight, the researchers said.

With obesity on the rise in many parts of the world as people eat fattier diets and get less exercise, scientists are eager to find new ways to combat the problem. These findings could help guide efforts to create better drugs to suppress appetite and reduce obesity, the researchers said.

"Clearly what we have in mind is trying to find new approaches that regulate food intake. And this may be a new pathway that one could target to treat obesity," Shulman said in a telephone interview.

"We're now doing the fat-feeding studies in humans to see if we get a similar increase in plasma (blood) NAPE concentrations following a fatty meal," Shulman added.

Scientists are working toward a greater understanding of how the body tells the brain to control food intake. Hormones such as leptin that help regulate this system have proven disappointing when examined as human weight-loss treatments.

(Editing by David Wiessler)

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