University of Colorado Professor Receives International Acclaim for Obesity Research

Denver (March 11, 2013) — Professor James McManaman, Ph.D., vice-chairman of research for the University of Colorado School of Medicine’s Obstetrics and Gynecology Department is the subject of worldwide attention as the lead author of a study discovering that deleting a specific gene in mice prevents them from becoming obese even on a high fat diet, a finding he and his colleagues believe may be replicated in humans.

“When fed a diet that induces obesity these mice don’t get fat,” said McManaman. “It may be possible to duplicate this in humans using existing technology that targets this specific gene.”

Funded by the National Institutes of Health and the U.S. Department of Agriculture, the study was published last month in The Journal of Lipid Research. McManaman has been featured on national and international broadcasts, as well as in newspapers around the world.

“Obesity is a problem for a variety of concerns for obstetricians and gynecologists,” said McManaman, explaining why the CU OB-GYN department was involved in this research. “There are problems with obesity during pregnancy and fetal outcomes with children in terms of becoming obese. There’s a clear role of obesity in certain kinds of cancers our faculty gynecologists treat, such as endometrial and breast cancer.”

McManaman and the research team created a strain of mice without the Plin2 gene, which produces a protein that regulates fat storage and metabolism. The mice exhibited resistance to obesity, eating less and even becoming more active.

The mice without the Plin2 gene were healthier, with lower levels of triglycerides, fat cells 20 percent smaller than in normal mice, and no fatty-liver disease associated with obese rodents and humans, who also have the Plin2 gene. The reason may be that the absence of the gene may cause fat to be metabolized faster.

“It could mean that we have finally discovered a way to disrupt obesity in humans,” McManaman said. “The next steps are to try to figure out exactly how the loss of this gene affects the development of obesity from the standpoint of physiology and molecular mechanisms. If we understand how it is working at the molecular level, that opens up new avenues of therapy in trying to treat obesity. We need to know if we can knock out this gene or disrupt its function once a person is obese.”

In addition to McManaman, the study’s co-authors include David Orlicky, Ph.D., and Paul MacLean, Ph.D., associate professors at University of Colorado School of Medicine, as well as Andrew Greenberg, MD, senior scientist and director of the The Obesity and Metabolism Laboratory at Tufts University.

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