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Protein May Hold Key to Obesity, Diabetes

How do diets high in carbohydrates lead to obesity and diabetes? Researchers have found a single protein -- carbohydrate response element binding protein (ChREBP) -- activates several genes that cause cells in the liver to turn sugar into fat.

Eating meals high in carbohydrates or sugars leads the body to do several things. Some sugars are immediately converted to energy while the rest 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.
  • 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.

The ChREBP protein is referred to as a transcription factor that works 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 the energy production pathway to build fat for energy storage when glucose consumption exceeds the body's energy needs.

In one study, researchers found when mice couldn't manufacture ChREBP, they had high levels of glucose in their bloodstreams, a condition commonly known as glucose intolerance which is often seen in patients with diabetes. Then, researchers fed the mutant mice a high-carbohydrate diet. Unable to convert the large excess of sugar into fat, the mice could not create enough energy to survive.

EurekAlert October 18, 2004

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