Scientists say they may have found out why people get hungry at mealtime, why dieters who lose weight often gain it back and why a certain type of stomach surgery helps very obese people lose a great deal of weight.
The reason may be a hormone called ghrelin, which makes people hungry, slows metabolism and decreases the body’s ability to burn fat.
Ghrelin levels in the blood spike before meals and drop afterward. People given ghrelin injections felt voraciously hungry, and, when turned loose at a buffet, ate 30 percent more than they normally would.
Dieters who lose weight and then try to keep it off make more ghrelin than they did before dieting, as if their bodies are fighting to regain the lost fat, researchers are reporting today in the New England Journal of Medicine.
By contrast, the same study showed that very obese people who have an operation called gastric bypass to lose weight wind up with relatively little ghrelin, which may help explain why their appetites decrease markedly after the surgery.
Ghrelin Acts on Brain to Stimulate Hunger
Ghrelin is one of a complex array of natural substances that carry messages between the brain and the digestive system. Secreted by specialized cells in the stomach and the upper part of the small intestine, ghrelin acts on the brain. It is the first natural appetite stimulant found to be made outside the brain.
Because it occurs outside the brain, it may be a relatively easy target for scientists looking for ways to manipulate weight.
Weight Loss Drugs to Block Ghrelin
If drugs could be developed to decrease ghrelin levels or block its action, they might help people lose weight, researchers say. And finding drugs that could mimic ghrelin’s action might stimulate appetite in people who are wasting away from cancer, heart failure, aging or eating disorders.
“It would be interesting to know what would happen if we could block the rise of ghrelin,” said Dr. David Cummings, the first author of the new study and an endocrinologist at the University of Washington and the Department of Veterans Affairs in Seattle. “Would it facilitate weight loss, or make it easier to lose weight through dieting or exercise?”
Cummings said, however, that it might be easier to use ghrelin to help people who need to gain weight. He said ghrelin might be an important part of the body’s system for defending itself against starvation.
“A powerful mechanism to increase appetite and decrease metabolism when weight loss occurs is likely to have evolved because our species was subjected to periods of famine, and the threat to survival came from starvation, not overnutrition,” he said. “People with an array of genes that promoted gluttonous consumption in times of plenty and efficient storage of fat might survive and pass on those genes, while the finicky eaters would die.”
But in the developed world, Cummings said, “where we have continuous access to highly caloric, highly palatable food and no need to work to get it, those genes do us a disservice.”
Ghrelin and Obesity
He and other researchers caution that the research is in its early stages. Cummings said ghrelin is not likely to be the cause of most obesity, and further experiments are needed to find out whether it will lend itself to new therapies.
Jules Hirsch, an obesity expert at Rockefeller University in Manhattan, said ghrelin clearly had a “profound effect on appetite.” But, he added: “Whether it will be useful in any way in the treatment of obesity remains to be seen. There are so many redundant loops that something else may take over to restore the fat that people want to lose.”
Leptin Appetite Suppressant
Another promising discovery, leptin, an appetite suppressant made by fat cells and thought to have great promise as a treatment for obesity, has turned out to be a disappointment because most overweight people are resistant to its effects.
Ghrelin was first described by Japanese researchers in the journal Nature in December 1999. They chose the name ghrelin because “ghre” is the Proto-Indo-European root of the word “grow,” and ghrelin also stimulates the pituitary gland to release growth hormone.
Ghrelin soon became a hot topic of research, and scores of scientific papers about it have already been published. The studies reported today are the first to measure its levels in dieters and people who have had weight-loss surgery.
Cummings and his colleagues measured ghrelin levels in three groups of people: 10 who had normal weight, 13 who were obese but had lost weight by dieting and five who were still obese but who had lost large amounts of weight after gastric bypass surgery.
The dieters were put on a liquid formula diet that provided 1,000 calories a day for three months. They lost 17 percent of their body weight, and then for three months switched to a more normal eating plan meant to maintain their weight.
Their ghrelin levels were measured before they began dieting and again six months later. The levels were markedly higher after the weight loss.
That finding may help explain why diets fail for the majority of overweight people; the most they can realistically hope to lose is 5 percent to 10 percent of their body weight, and keeping off even that amount usually requires a lifelong struggle.