Mice without ChREBP
The researchers used four groups of mice. One group lacked a functional ChREBP gene. Because these mice were unable to synthesize ChREBP, they converted very little carbohydrate to fat and remained relatively thin, even when they ate a very high carbohydrate diet, Uyeda explained.
The second group was a strain of obese mice that do not produce leptin, a hormone that tells us to stop eating when we are full, Uyeda said. "Since these mice don't make leptin, they eat large amounts of food, become obese and develop symptoms of insulin resistance and type 2 diabetes," he said.
The third group was a combination of the first two: They did not produce leptin and so were prone to obesity but they also lacked the functional ChREBP gene, which tends to keep mice lean. The fourth group of normal mice acted as controls.
"We found that the third group (that did not have ChREBP and did not produce leptin) did not become obese, had lower blood glucose levels than the obese group and were less insulin resistant," Uyeda said. "We also were very surprised to find that these mice ate much less than the obese mice of the second group."
"These results show the important role ChREBP plays in metabolism and appetite control in mice and, presumably, humans," Uyeda said. "Ultimately we hope to develop drugs to inactivate and control ChREBP to overcome these two major health problems of obesity and diabetes."
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Contact: Christine Guilfoy
cguilfoy@the-aps.org
301-634-7253
American Physiological Society
30-Aug-2006