Researchers discover master metabolism regulator with profound effect on fat ...( nd obesity is reaching near-epidemic p...)

Rather than working with cells in culture, Guo and Cavener examined metabolic processes in a special strain of mice that lacks the GCN2 kinase and compared them with those of normal mice. "Organisms are remarkably sensitive to dietary intake," Cavener says. "Being deprived of even one essential amino acid is enough for the GCN2 kinase to switch the metabolism into an emergency mode. Despite the fact that these mice are consuming normal amounts of carbohydrates and fats, they rapidly shut down fat synthesis in the liver and mobilize their stored fat deposits. Their bodies are literally tricked into a starvation mode."

The experiments conducted by Guo and Cavener had striking and unexpected results. After 17 days of a leucine-deficient diet, the normal mice lost 48 percent of their liver mass and 97 percent of the adipose or fatty tissue from their abdomens. This response is very similar to what happens during starvation. In contrast, the mice without the GCN2 kinase kept a steady liver mass and lost only 69 percent of the adipose tissue on their abdomens.

One of the especially encouraging aspects of the research by Guo and Cavener was the short time frame in which dramatic changes could be induced. Even after only 7 days of leucine deprivation, the normal mice lost 50 percent of their fatty tissue. They also produced fewer lipids (fats) and showed a small drop in serum triglyceride levels. The mice lacking the GCN2 kinase did not lose as much fat as the normal mice did and, in addition, they developed very pale, fatty livers with unusually high levels of stored triglycerides because they continued to synthesize fatty acids. The remarkable rapidity of the weight change in the normal mice occurred because the repressed synthesis of new fats was coupled w
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Contact: Barbara K. Kennedy
science@psu.edu
814-863-4682
Penn State
6-Feb-2007