UT Southwestern researchers uncover process for sugar-induced fat formation

DALLAS Oct. 18, 2004 Researchers at UT Southwestern Medical Center at Dallas are one step closer to understanding how high carbohydrate diets lead to obesity and diabetes.

Dr. Kosaku Uyeda, professor of biochemistry, has shown that a single protein called carbohydrate response element binding protein (ChREBP), discovered by his research group, activates several genes that cause cells in the liver to turn sugar into fat.

Their work appears in two studies in Proceedings of the National Academy of Sciences. The first study, published in an earlier issue, is available online, and the second, also online, will appear in an upcoming issue of PNAS.

"Purifying ChREBP from rat livers took two postdoctoral fellows two years of very hard work," said Dr. Uyeda, senior author of both studies and a research scientist at the Veterans Affairs North Texas Health Care System. "With the discovery of this factor, the biochemical mechanism of how carbohydrates are converted to fat has become clearer."

Eating meals high in carbohydrates or sugars leads the body to do several things. Some of the sugars are immediately converted to energy while the rest of the sugars are converted to fat. The sugar-to-fat conversion occurs two ways an immediate response, where enzymes are mobilized to rapidly convert sugars into fat; and a slower response, in which several different genes are turned on and off, creating more enzymes that can also turn sugar into fat. ChREBP is involved in the slow response.

ChREBP is a type of protein called a transcription factor. Transcription factors work in the cell nucleus to turn genes on and off in response to a signal. In the case of ChREBP, the signal is glucose, a simple sugar formed when carbohydrates are broken down during digestion. Glucose enters the bloodstream and, through transport molecules, enters cells where it is broken down into even smaller pieces. These smaller pieces are diverted from th

Contact: Megha Satyanarayana
UT Southwestern Medical Center

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