What triggers hunger? This is a million-dollar question that has plagued the scientific community for decades. Researchers have argued everything from a contracting stomach to low blood sugar to answer this question, but no consensus has been reached.
Now, two years after its discovery as an appetite stimulant, a hormone termed ghrelin is gaining wider acceptance as the body's mechanism for communicating hunger.
First identified in 1999, ghrelin was originally recognized for its role as a growth hormone regulator. One year later, scientists demonstrated that ghrelin injections in rodents resulted in stimulated feeding. When research efforts were extended to human subjects, ghrelin levels were found to rise sharply before mealtimes and dive shortly thereafter. More recently it has been found that chronic ghrelin administration fuels the human appetite'prompting people to eat nearly 30 percent more on average.
The word ghrelin stems from the Hindi root \ghre,"" which means growth. As its name indicates, ghrelin was first associated with the stimulation of growth hormone secretion. While its receptors reside in the brain, the site of ghrelin production turned out to be the stomach.
""Ghrelin is produced by the stomach, circulates within the blood, then travels to the brain and seems to interact with targets called receptors,"" said David Cummings, a leading personality in ghrelin research at the University of Washington.
Pioneering ghrelin research at Lilly Research Laboratories in Indianapolis showed that rats injected with ghrelin gained weight as fat tissue. They found that ghrelin, in addition to controlling growth hormone release, signals the brain to regulate metabolism.
Patients were first injected with ghrelin to stimulate the release of growth hormone, a protein crucial for development, tissue repair, muscle growth and bone strength. When a majority of subjects complained of extreme hunger, ghrelin's link to the human appetite was first established.
The molecular mechanisms for controlling body weight are of utmost interest to scientists and the general population alike.
""Studies indicate your weight is maintained remarkably stable over time,"" Cummings said. ""Fifty to 80 percent of determinants of body weight are genetic. Your genes put you in a body-weight ballpark. Within that ballpark, you have the possibility to slide up or down 5 to 10 percent with diet and exercise.""
For years leptin, a hormone secreted by fat cells, was the body's only known chemical signal for hunger. Leptin communicates the status of fat stores to the brain's hypothalamus, which coordinates basic body functions such as eating. Increased leptin levels are thought to stimulate appetite and slow metabolism.
Since leptin levels do not rise and fall dramatically during the day, however, it seems logical that the body has additional shorter term mechanisms for translating ""eat"" messages to the brain.
""You're hungry at dinnertime even when you eat lunch that same day. Something else besides leptin is governing when you feel hungry. Now ghrelin has surfaced as a potential candidate for that,"" Cummings said.
Some of the most interesting studies on ghrelin involve patients suffering from. People suffering from wasting syndromes, such as anorexia nervosa, actually produce more ghrelin than normal'not less. The highest concentrations of ghrelin in the blood ever reported, in fact, occurred in people starving themselves to death.
One might expect that obese people would also overproduce ghrelin, causing them to eat more. However, more often the opposite is true.
""Overweight people have suppressed ghrelin levels in the plasma,"" said Eric Ravussin, a professor at Pennington Biomedical Research Center in Baton Rouge, La.
Scientists have not yet unlocked the relationship between obesity and ghrelin. ""Cross-sectional data will never tell you cause and effect,"" says Ravussin.
Thus far ghrelin has been found to affect many aspects of physiology, including blood pressure, sugar concentrations and insulin metabolism. Such evidence implies a complicated role for ghrelin, a seemingly simple peptide. And while ghrelin seems to offer an answer to our hunger pangs, we may not be able to boil weight control down to a single hormone.
