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Hormone Ghrelin Raises Desire for High-Calorie Foods

Development of Drugs to Block Ghrelin May Some Day Help in Fight Against Obesity

By Kathleen Doheny
WebMD Health News

Reviewed By Laura J. Martin, MD

June 22, 2010 -- High levels of the appetite hormone ghrelin appear to make high-calorie foods look more appealing, perhaps explaining why you choose chocolate cake over salad, according to a new study.

So strong is the effect of high ghrelin levels that it mimics fasting, says Tony Goldstone, MD, PhD, senior clinician scientist at MRC Clinical Sciences Centre at the Imperial College of London and Hammersmith Hospital, who presented his findings at a news conference at ENDO 2010, the annual meeting of the Endocrine Society, in San Diego.

''Both fasting and the administration of the hormone ghrelin, which is high when we are fasting, increase the appeal of high-calorie foods but not low," Goldstone says.

In his study, he found that ghrelin may influence our eating behavior partly through stimulating the brain reward systems, which became more active when his study participants were given ghrelin than when they weren't given injections of the hormone.

Ghrelin and the Appeal of High-Calorie Foods

Ghrelin, which originates in the stomach, declines soon after meals. ''Ghrelin levels in the blood are high before we eat our food," Goldstone says. "When you eat a meal, the levels of ghrelin come down and then rise again before lunchtime. If you give ghrelin to an individual, they will eat more."

He set out to investigate whether the effect of fasting on food selection -- that feeling of hunger that drives you to eat anything in sight -- is mimicked with injections of ghrelin.

For the study, 18 healthy, non-obese men and women, average age 23, fasted overnight and then came into the study center on three separate days, at least a week apart.

Goldstone assigned them either to a group that kept fasting or a group that ate a 730-calorie breakfast, rotating them through the scenarios.

Next, the participants were either injected with saline or the ghrelin, not knowing which they were receiving, again rotating them through each condition. To verify that the ghrelin had a biological effect, Goldstone says, they confirmed that growth hormone -- which is known to rise when ghrelin is given --did indeed increase.

Finally, participants were shown pictures of high-calorie or low-calorie foods, 60 of each, and asked to rate the appeal of the foods by giving each picture a score of 1 to 5. High-calorie options included chocolate, pizza, burgers, and other foods. Low-calorie foods included fish, vegetables, and salads. For comparison, the participants also looked at non-food pictures showing common household objects.

While participants rated the foods, a functional MRI recorded their brain activity.

Ghrelin and the Appeal of High-Calorie Foods: Results

The appeal of high-calorie foods was higher when participants were either fasting and given saline or fed and given ghrelin compared to the visit when they got breakfast and were given saline. The effect was particularly evident for sweet, high-calorie food, Goldstone says.

"For the low-calorie foods, there was no difference in appeal between the three visits,'' Goldstone says, regardless of whether the participants were fed or not or had saline or ghrelin injected.

Goldstone also looked at how the appeal of the foods affected a part of the brain called the anterior orbital frontal cortex, ''known to be involved in encoding the reward value of food," Goldstone says.

The activation of this area declined when participants were fed but went back up when they were fed but given ghrelin.

''Thus, it appears that both acute fasting and ghrelin bias the reward systems to [choose] high-calorie foods," he says. "Changes in the hedonics of food -- how pleasurable we find food -- after missing meals or eating may be explained by levels of ghrelin circulating in the blood."

The research may provide more clues, Goldstone says, as to why so much of the population is obese or struggling with binge eating or other food issues. About one-third of U.S. adults are obese, according to the CDC, although the increase in obesity may be slowing.

In the future, Goldstone says, the development of drugs to block ghrelin may help in the obesity struggle.

Second Opinion

''It's fascinating how hormones can make you interested in chocolate," says Daniel Bessesen, MD, an endocrinologist and professor of medicine at the University of Colorado Denver, who moderated the news conference.

Science is evolving on how the brain controls food intake, he says. "It's not all about hunger, There is also this attractiveness of food. I think the attractiveness of food is part of why we overeat these days.''

Of the new research by Goldstone, Bessesen says: "His point is there is a biological basis for that [attractiveness]. His research shows, if you haven't eaten, it turns up the attractiveness of food."

Even so, ''the message doesn't have to be hopeless," Bessesen tells WebMD. The information can help alert you to why you're sometimes attracted to certain foods -- and try to override that appeal.

How to Outsmart Your Ghrelin

Goldstone agrees that even with high levels of ghrelin, you don't have to be at the mercy of your hormones. ''There are a couple of studies suggesting the orbital frontal cortex activity can be modified," he says.

Among those who do it best, he says, are people who are most concerned about maintaining a healthy weight -- who exercise what researchers call dietary restraint.

In another study, Goldstone says, he found that those with high dietary restraint scores had less activity in the orbital frontal cortex. The executive decision-making part of their brains seems to override the reward system activation, he says.

Eventually, ghrelin-blocking drugs may make it easier to pick the salad over the chocolate ice cream, but until then? "The advice not to skip breakfast comes out again with this study," Goldstone says. Other times of the day, eating before you are famished can help, too, he says.

This study was presented at a medical conference. The findings should be considered preliminary as they have not yet undergone the "peer review" process, in which outside experts scrutinize the data prior to publication in a medical journal.

SOURCES:

ENDO 2010, 92nd Annual Meeting & Expo, The Endocrine Society, San Diego, June 19-22, 2010.

Tony Goldstone, MD, PhD, senior clinician scientist, MRC Clinical Sciences Center, Imperial College of London, Hammersmith Hospital.

Daniel Bessesen, MD, professor of medicine and endocrinologist, University of Colorado, Denver.

CDC: "Overweight and Obesity Trends Among Adults."

© 2010 WebMD, LLC. All rights reserved.



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