Study of Mice Ties Chemical In the Brain To Overeating
Published: December 6, 1996
WASHINGTON, Dec. 5— Blocking a brain chemical can curb appetites in mice, researchers have found in an experiment that helps explain why a flawed ''fat gene'' can help cause obesity.
Working with mice that were genetically altered to be extremely obese, researchers found that the weight gain was controlled, in part, by the action of a brain chemical called neuropeptide Y, or NPY, said Dr. Jay C. Erickson, a Howard Hughes Institute researcher at the University of Washington.
Dr. Erickson said that mice with a flawed gene called OB fail to produce leptin, an appetite-control protein. Without leptin, the appetite is voracious and unending. Mice with a flawed OB gene eat without restrain and become grossly fat, sterile, diabetic and lethargic.
When neuropeptide Y is genetically removed from this rodent breed, however, the mice slim down, become more energetic and can even reproduce. The absence of the neuropeptide suppressed the appetite, Dr. Erickson said.
''NPY is the reason for about half of the obesity caused by a lack of leptin,'' he said. ''It is only part of the puzzle. There are other elements that stimulate the urge to eat. There are a half dozen other substances or even some genes that also contribute to obesity.''
The results of the study by Dr. Erickson and two other authors will be published on Friday in the journal Science.
The finding is important, said Dr. Jeffrey Friedman of Rockefeller University in New York, one of the discoverers of the OB gene, but the relationship between chemicals that control body weight ''is a complicated one'' and Dr. Erickson's work links only two of the elements. ''Much is left to be done to identify all of the other components,'' Dr. Friedman said. ''The more we understand this, the more likely that some therapy will be developed.''
Dr. Erickson and his colleagues genetically engineered mice to lack the genes for both leptin and for neuropeptide Y. Another group of animals, called OB/OB mice, lacked the leptin gene but had the neuropeptide Y gene. Another group of mice had normal genes. All were then allowed to eat as much as they wanted.
''Earlier studies had shown that the OB/OB mice had an excessive amount of NPY in the brain,'' Dr. Erickson said. ''It contributes to the drive to eat. We wanted to see if removing that neuropeptide had any effect on appetite.''
The effect was obvious after 16 weeks. The OB/OB mice, those lacking leptin but with neuropeptide Y, ate 62 percent more than normal mice and were extremely obese. The double mutant mice, those lacking both leptin and neuropeptide Y, ate 35 percent more than the normal mice and were fatter than normal mice, but they were only about half as hefty as the OB/OB mice.
Dr. Erickson said it was not known how this research would be applied to humans. ''We don't know what NPY is doing in humans who are obese,'' he said, ''so we can't necessarily extrapolate from the findings in mice to humans.''