Daniele Piomelli, professor of psychiatry and pharmacology, and colleagues found that the fatty acid, called OEA (oleylethanolamide), activates its cell receptor molecules to regulate hunger and metabolism. The team also discovered that by increasing OEA levels while maintaining normal levels of these cell receptors, they could reduce appetite and weight in rodents, as well as lower their blood cholesterol and triglyceride levels.

The study appears in the Sept. 4 issue of Nature. "In earlier studies, we found that OEA can be an important regulator of eating behavior, but we didn't know how it worked," Piomelli said. "We were excited to find that OEA activates cell receptors that have already been the focus of successful drug development. This gives us hope for a new class of anti-obesity drugs based on natural chemicals."

To test the role of OEA and its receptors, Jin Fu, Silvana Gaetani, Fariba Oveisi and Jesse Lo Verme on the Piomelli team fed a high-fat diet to two groups of mice one a group of regular mice, the other a mutant group with its OEA cell receptors genetically removed. After the mice became obese, they were treated with OEA for four weeks. Normal mice ate less and lost weight, while OEA had no effect on the group that lacked the cell receptors, suggesting that OEA only can reverse weight gain when active cell receptors are in place.

They also found that in normal mice, OEA lowered blood cholesterol and triglyceride levels by reducing levels of hunger-inducing nitric-oxide molecules. These reductions were not seen in the mutant mice group.

"This shows the receptors are not only necessary for the hunger-curbing and weight-reducing actions of OEA, but may cont
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Contact: Tom Vasich
tmvasich@uci.edu
949-824-6455
University of California - Irvine
3-Sep-2003