Study finds those given injections of ghrelin showed activity in brain's reward centers
WEDNESDAY, May 7 (HealthDay News) -- A new brain imaging study reveals that a gut hormone known for its appetite-promoting powers actually stimulates key reward centers in the brain to make food look more tasty and irresistible.
The feeding culprit is ghrelin, and the finding suggests that this hormone's so-called "hedonic effect" on the senses unfolds in the same brain regions that researchers have long-associated with drug addiction -- motivating people to eat even when there is no nutritional reason to do so.
"For hundreds of years, people used to think that you eat only because you're hungry," observed study author Dr. Alain Dagher, an associate professor with the Montreal Neurological Institute of McGill University, in Canada. "But we found that the actual system involves a drive for food that is not at all related to hunger."
"The reason for this," he added, "is that almost every animal -- including us, until very recently -- was living in a world where there wasn't enough food, so that the big risk is starving to death. This creates a real pressure to eat. And obtaining food is risky. It requires effort and putting yourself at the mercy of predators. So you need something to get you out of your cave, and the only way that's going to happen is if the food is attractive enough to get you to overcome those costs and risks. And we've found a hormone that does this by acting on the pleasure and reward centers of the brain and making food you see seem more appealing and more desirable."
Dagher and his colleagues reported their findings in the May issue of Cell Metabolism.
The authors analyzed functional MRIs of brain activity among 20 healthy men while they viewed food and non-food imagery.
Within three hours of eating a standard breakfast -- so that the men were neither full nor hungry -- all viewed an initial series of 45 images during which they answered questions about their mood and appetite.
Following the first viewing, 12 of the men received two intravenous infusions of ghrelin, while the other eight did not.
Following blood sampling to gauge hormonal levels, the men viewed a second set of 45 different images.
Dagher and his associates found that during the second viewing, reports of hunger were significantly higher among men who received an infusion of ghrelin.
This increased hunger response correlated with an increase in brain activity in a broad range of brain regions associated with reward -- but only when viewing food imagery. Activated regions included the amygdala, the right hippocampus, the anterior and mid-dorsal insula, and the left pulvinar regions.
By contrast, men who never received ghrelin expressed no change in hunger over the course of the two viewing sessions and were less likely to remember the food imagery they saw following the viewings.
The researchers suggested that the findings could ultimately lead to treatments for obesity based on a disruption of the ghrelin effect.
"The problem today is that we have this evolutionary imperative to eat, but we now live in an environment where you don't have to spend any energy to get food," he noted. "Which means that it makes sense to think of appetite as a kind of addiction. So, if we want to address the fact that obesity is now the number one killer in the world, we're going to have to tackle the problem in the same way that we tackle cigarette smoking."
But Dr. Barbara B. Kahn, chief of the division of endocrinology, diabetes, and metabolism at Beth Israel Deaconess Medical Center in Boston, cautioned that equating ghrelin-fueled overeating with drug addiction may do a public disservice.
"This study provides us with new information about additional ways in which this particular hormone may work," she said. "And overeating and drug addiction may converge on some of the same neurons. But other pathways are also involved. And from a biochemical point of view, the two are not the same thing. Drug addictions are much stronger. So to suggest that they are the same makes people feel that they can't do anything about overeating. That it's out of their control.
"So, I don't really buy that the parallel," added Kahn. "There may be aspects of overeating that may be related to aspects of addiction. But overeating is not just another addiction."
In the same journal, a separate animal study out of Duke University Medical Center highlights a potentially new way to help people curb their appetites and achieve weight control.
Study researchers report that by blocking activation of a key brain enzyme (CaMKK2), they were able to short-circuit the normal flow of the ghrelin pathway in mice, preventing the activation of a second enzyme (AMPK) that directly triggers the desire to eat. The finding, they said, appears to open up a fresh target for drugs geared at reducing appetite.
For additional information on weight management, visit the National Institute of Diabetes and Digestive and Kidney Diseases.
SOURCES: Alain Dagher, M.D., associate professor, Montreal Neurological Institute of McGill University, Montreal; Barbara B. Kahn, M.D., chief, division of endocrinology, diabetes and metabolism, Beth Israel Deaconess Medical Center, and professor, medicine, Harvard Medical School, Boston; May 2008, Cell Metabolism
All rights reserved