Rutgers researchers have identified a gene - and the molecular function of its protein product - that provides an important clue to further understanding obesity and may point the way to new drugs to control fat metabolism.
The scientists found that the human protein known as lipin is a key fat-regulating enzyme. "Lipin activity may be an important pharmaceutical target for the control of body fat in humans, treating conditions that range from obesity to the loss of fat beneath the skin, as seen in HIV patients, " said George M. Carman, a professor in Rutgers' department of food science.
In a paper published online by the Journal of Biological Chemistry (print version, April 7), Carman and his research team at Rutgers' Cook College describe their scientific detective work, moving from clue to clue in a series of logical connections to reach their discoveries.
Previous studies with mice showed that a lack of lipin causes a loss of body fat, whereas an excess of lipin promotes extra body fat. So researchers knew that lipin was involved in fat metabolism; they just didn't know how.
The Carman team's first revelation came with the discovery that lipin is an enzyme (phosphatidic acid phosphatase or PAP), a protein catalyst that is required for the formation of fats - triglycerides, specifically.
The breakthrough for Carman's group grew out of work with ordinary baker's yeast; a simple single cell organism. "We isolated the PAP enzyme from yeast that corresponds in form to lipin in mammals and showed that yeast cells lacking the enzyme exhibited a 90 percent reduction in the yeast's version of fat loss," Carman said.
The group worked out the sequence of the amino acids that make up the PAP enzyme, allowing them to backtrack along the path to its origin - the gene that coded it - linking the enzyme to the yeast gene PAH1 that made it. Carman and his group went on to confirm the link by introducing the yeast gene into bacteria, with similar results.