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Credit: Joseph Blumberg
Professor George Carman, right, examines
yeast cultures with Gil-Soo Han,
research associate, in the laboratory at
Cook College, where a 16-year-old frozen
test-tube specimen was discovered in a
freezer. The specimen led researchers to
discover a gene that plays an important
role in controlling body fat, a
potential target for new weight loss
drugs.
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Researchers at Cook College have identified a human gene, its protein product and the way in which the protein influences how the body processes fat – discoveries that may lead to drugs to control obesity and promote weight loss.
The so-called “fat gene” carries the code for lipin, a protein that is key to controlling fat metabolism in humans and animals, said George M. Carman, professor of food science, who led the research team.
These findings are all the more remarkable given their origins: a 16-year-old leftover frozen test-tube specimen found in a laboratory freezer.
This scientific detective story began in 1989, when graduate student Yi-Ping Lin purified a small amount of a yeast enzyme known as PAP, a protein catalyst required for the formation of fats.
At that time the technology was not refined enough to determine the enzyme’s sequence and identify its gene, so the project was shelved.
While cleaning out a 7-foot-high deep-freezer last summer, Carman’s crew found some of the PAP enzyme that had been purified again in 1993 by another graduate student, Wen-I Wu. “Because we now had the technology, my postdoctoral associate Gil-Soo Han was able to get a sequence of the amino acids in PAP this time around,” Carman said.
Previous studies with mice have shown that a lack of lipin causes a loss of body fat and that excess lipin promotes extra body fat. So scientists knew that lipin was involved in fat metabolism; they just didn’t know how.
Carman and his research team’s first revelation that lipin might be targeted for control of body fat came with the discovery that the protein is a PAP enzyme. Since they had worked out the sequence of the amino acids that make up the yeast PAP enzyme, they were able to backtrack along the path to its origin – the gene that coded it – linking the enzyme to the yeast gene PAH1 that made it.
“This is a big breakthrough because for years, no one was able to get the gene for PAP and prove that it was important in making fat,” Carman said. He said the discovery could have implications for treating conditions that range from obesity to the loss of fat beneath the skin, as seen in HIV patients.
The findings are published in the April 7 issue of the Journal of Biological Chemistry.
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