Scientists say they have demonstrated, for the first time, how a newly discovered and purified protein regulates control of feeding behavior. The research, done at Amgen in Thousand Oaks, Calif., could lead to new strategies for treating obesity.
Details of this development are in the November 17 issue of the peer-reviewed journal Biochemistry, which is published by the American Chemical Society, the world's largest scientific society.
Obesity researchers have been increasingly interested in a brain system called the melanocortin pathway. "The evidence is really piling up that this pathway is likely to be important in the regulation of food intake by the brain," says Amgen scientist Kevin Stark, Ph.D. When the alpha-melanocyte stimulating hormone (alpha-MSH) binds to melanocortin-3 or melanocortin-4 receptors in the brain, the pathway is activated and signals are sent to reduce food intake.
Scientists at Amgen had previously found a gene, called Agrp, that they suspected to be an important regulator of the melanocortin pathway. Now they have shown that the product of that gene, a protein they call AGRP, blocks the binding of alpha-MSH. The researchers believe the likely result is increased food consumption. While this might be desirable sometimes, too much AGRP may be a problem.
Previous work by the Amgen scientists also has shown that levels of AGRP are about ten-fold higher in mice which are genetically obese, or have fasted. While no studies have been reported yet on the levels of AGRP in humans, previous research by other groups shows two genes that interact with AGRP in this pathway (those for alpha-MSH and the melanocortin-4 receptor) are mutated in some obese humans.
A number of other genes such as leptin appear to be related to obesity. However, now that the mechanism of action of purified AGRP is known, Amgen researchers think it reveals another potential point of attack for an anti-obesity drug. The challenge will be designing a drug that prevents AGRP from binding to receptors within the melanocortin system.
A nonprofit organization with a membership of more than 155,000 chemists and chemical engineers, the American Chemical Society publishes scientific journals and databases, convenes major research conferences, and provides educational, science policy and career programs in chemistry. Its main offices are in Washington, D.C., and Columbus, Ohio.
Journal
Biochemistry