Chemical May Hold Key to Feeling of Hunger
Tweezing apart the complex brain mechanisms that control hunger, scientists at two La Jolla institutes have shown that a newly discovered nerve chemical sharply reduces appetite, prompting even starved rats to turn their whiskered noses away from food.
Though the experiments involved lab animals, the work by researchers at the Scripps Research Institute and the Salk Institute may partially explain the biology of human eating disorders such as anorexia nervosa, in which someone who desperately needs food shuns it.
The researchers speculate that sustained psychological stress could prompt the brain to produce an excess of the chemical, called urocortin, making it easy to avoid eating. On the other hand, a shortage of urocortin in the brain might prompt a heightened appetite that could lead to obesity, the researchers suggest.
“If we get to understand what the mechanism is of how [urocortin] works, then it’s possibly going to be helpful in the management of eating disorders,” said Scripps neuroscientist Mariarosa Spina, the study’s lead author. The work is being published today in the journal Science.
It is possible that scientists could develop a drug that either blocks the action of urocortin, or an analog that mimics it, the researchers said, thereby alleviating an eating disorder by compensating for either an excess or shortage of the nerve chemical.
Urocortin is closely related to another long-studied brain chemical called corticotropin-releasing factor, which plays a central role in mediating numerous bodily responses to stress, including reducing appetite, raising blood pressure and ultimately unleashing the adrenaline that propels “fight or flight” responses.
In contrast, urocortin seems largely limited to reducing appetite, which makes it especially attractive as a basis for drug development.
To be sure, the researchers have not yet studied whether the human brain produces urocortin, but they have much indirect evidence that it does. Genetic tests show that human cells contain the DNA necessary for making the substance, said Wylie Vale, a Salk scientist who collaborated on the new research and was part of the team that discovered urocortin last year.
In the study, the researchers injected microgram amounts of urocortin directly into the brains of rats who had not eaten for a day. When food appeared, those rats ate much less than did other rats whose brains were injected with a dummy liquid.
The researchers believe that the urocortin did not simply make the rats sick to their stomach, since animals in another set of experiments that were given unrestricted access to food nibbled at it as often as did untreated animals--they just ate much less of it. Also, the experimental animals drank just as much water as the controls, suggesting that the brain chemical has little effect on thirst.
Because of the chemical makeup of urocortin--it is a largish molecule known as a peptide, and would not readily pass from the bloodstream into the brain--the substance itself is not likely to be commercially developed as a drug. So researchers may focus on creating urocortin analogs.
The Salk Institute holds a patent covering exploitation of urocortin. And a commercial biotechnology firm that Vale co-founded, Neurocrine Bioscience, is among the companies zeroing in on the peptide’s potential as the basis of new drugs.
