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

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.

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