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Fat-Sensing Hormones Might Fight Obesity
Date:11/26/2008

Study with rodents shows the molecules help regulate appetite

WEDNESDAY, Nov. 26 (HealthDay News) -- As you push your chair back from the Thanksgiving table this year, a molecule produced in the small intestine will be swarming through your bloodstream, ready to register on your brain the impact of the fat you've just consumed.

For now, the signal might keep you feeling full for a while. But, researchers are hoping that one day variations of this family of hormones -- known as N-acylphosphatidylethanolamines, or NAPEs -- can be used to control appetite and therefore obesity.

"We're excited but we have to be cautious," said Dr. Gerald Shulman, senior author of a study in rats that's published in the Nov. 26 issue of the journal Cell. "We would love to be able to take this to man tomorrow because we need effective ways to treat obesity and, right now, we have very few agents that work effectively. But we have much work to do."

Shulman is an investigator at the Howard Hughes Medical Institute and a professor of internal medicine and of cellular and molecular physiology at Yale University School of Medicine.

Shulman's research team had been looking for a new, fat-derived signal that might regulate food intake. A sensitive blood-screening test -- called LC tandem mass spectrometry -- turned up the NAPE group of molecules.

Levels of NAPEs increased consistently in rats and mice that had just eaten a fatty meal. And when synthesized and re-injected into the lab rodents, NAPEs shut down the rodent's food intake, with one dose lasting 12 hours or longer. NAPEs also entered the brain, appearing to concentrate in the hypothalamus, an area with a high concentration of neurons involved in the regulation of food intake, the researchers said.

Rats receiving NAPEs chronically (through a catheter in the jugular) ate less and lost weight.

"That's what we have, a gut-derived fat that works centrally to inhibit food intake," Shulman said.

Shulman and his colleagues believe that aberrations in how NAPEs are secreted in people who eat lots of high-fat foods may contribute to obesity. "Some of our animal data suggests that NAPE secretion is dysregulated in our animal models of diet-induced obesity," Shulman said.

"We're moving up the species ladder to see if chronic NAPEs reduces food intake and is well-tolerated in non-human primates," Shulman said. "If everything there looks good, that would give us a lot of motivation to actually do trials in humans."

David Earnest, professor of neuroscience and experimental therapeutics at Texas A&M Health Science Center College of Medicine, said, "The NAPEs work to suppress appetite or decrease food intake, [but] feeding is a complex behavior. There are a lot of factors that figure into eating disorders. The findings are very interesting and exciting, basically because we have identified these NAPEs which are synthesized by the gut and presumably can be used in supplementary fashion to treat obesity in humans."

"Unfortunately, things don't always work out according to plan," he added. "Not to say that NAPEs don't offer hope. These are some encouraging observations."

More information

The U.S. Centers for Disease Control and Prevention has more on obesity and overweight.



SOURCES: Gerald Shulman, M.D., Ph.D. investigator, Howard Hughes Medical Institute, and professor of internal medicine and of cellular and molecular physiology, Yale University School of Medicine, New Haven, Conn.; David Earnest, Ph.D., professor of neuroscience and experimental therapeutics, Texas A&M Health Science Center College of Medicine; Nov. 26, 2008, Cell


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