By Suzanne Rostler

NEW YORK, Oct 24 (Reuters Health) - The results of an animal study provide new insight into how leptin, better known as the "obesity hormone," works to control appetite.

According to the investigation described in the October 25th issue of Nature, injecting rats with leptin activates an enzyme, PI(3)K, that is located in the brain's hypothalamus, which regulates a number of metabolic functions.

Blocking the PI(3)K enzyme increased the rats' appetite, the researchers report.

"Our data...suggest that this mechanism is critical for leptin's ability to control appetite," Dr. Michael W. Schwartz of the University of Washington in Seattle, told Reuters Health.

The findings suggest that defects in nerve cells that activate PI(3)K may be an underlying cause of obesity in humans. If current trials bear out this theory, scientists could develop drugs to activate the PI(3)K pathway and help individuals overcome leptin resistance, Schwartz said.

Leptin, a hormone produced by fat cells, circulates in the blood and tells the brain when cells are "full." In the brain, leptin activates receptors on nerve cells on the hypothalamus, an area tied to food intake.

In most people, body fat stores remain stable over time thanks to a biological system that involves leptin, Schwartz explained. Levels of the hormone fall in tandem with weight loss and as a result, appetite increases. Conversely, leptin rises in tandem with body fat and suppresses appetite, thereby facilitating a return to the original weight.

"We know that this action of leptin is critical because animals and humans lacking leptin or its receptor due to genetic mutations develop severe obesity," Schwartz said. "Weight regulation in normal people, therefore, appears to be critically dependent on leptin action."

Studies have shown that some obese individuals, who have very high leptin levels and a normal appetite, may be resistant to the hormone's appetite-suppressing effects.

"Understanding leptin resistance is therefore a major priority for understanding how obesity develops; overcoming it is a priority for improved obesity treatment," Schwartz said.

SOURCE: Nature 2001;413:794-795.

http://www.reutershealth.com/archiv...024elin012.html