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Disabling a carbohydrate trigger reduces obesity and appetite

BETHESDA, MD (August 30, 2006) Until about 15 years ago, insulin was believed primarily responsible for turning carbohydrates into fat. But then it became apparent that diet alone could stimulate glucose metabolism and fat synthesis, even when insulin levels were low or absent.

Five years ago, researchers discovered that a substance known as ChREBP (carbohydrate response element binding protein), quite independent of insulin, initiated a sequence responsible for converting excess carbohydrates to fatty acids for long-term storage.

In a study that appears in this month's edition of the American Journal of Physiology-Endocrinology and Metabolism, the same laboratory that identified ChREBP (pronounced "kreb") and its role in fat storage has discovered that the absence of ChREBP in mice keeps normally obese mice from becoming fat, lowers their blood triglycerides (a type of fat) and reduces the insulin resistance related to type 2 diabetes

The research, titled "Deficiency of carbohydrate-activated transcription factor ChREBP prevents obesity and improves plasma glucose control in leptin-deficient (ob/ob) mice," was carried out by University of Texas researchers Katsumi Iizuka, Bonnie Miller and Kosaku Uyeda of the UT Southwestern Medical Center, in Dallas. Uyeda is also associated with the Veterans Affairs Medical Center in Dallas. The American Physiological Society published the study.

"Carbohydrates are broken down into glucose and other simple sugars by digestion," explained Uyeda, the principal investigator. "These sugars enter the bloodstream and are mostly taken up by the liver." The liver does different things with the sugars, depending upon the body's energy needs. But if the body has enough energy, with the help of ChREBP, it converts glucose into fatty acids and stores it.

"Many people believe that evolutionary pressure favored those who could convert excess carbohydrate to fat and store it because they were bet
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Contact: Christine Guilfoy
cguilfoy@the-aps.org
301-634-7253
American Physiological Society
30-Aug-2006


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