Blocking a hunger-inducing hormone to help obesity might have unwanted effects.
It’s a classic mistake: you arrive at the grocery store hungry, and everything seems irresistible. Researchers have now worked out how a hunger-induced hormone called ghrelin can make all that food seem so desirable.
The hormone stimulates the same ‘reward centres’ of the brain that have been linked to drug-seeking behaviour, they say. But it also activates regions of the brain involved with making memories: people injected with ghrelin remember pictures of food more clearly a day later.
The appetite-stimulating effects of ghrelin are already being tested to see if the hormone can encourage eating in cancer patients. And inhibiting ghrelin has been discussed as one way to treat obesity. But the new results, published this week in Cell Metabolism1, suggest that drugs that block ghrelin may have unwanted effects on memory, says study author Alain Dagher of McGill University in Montreal, Canada.
Ghrelin was already known to trigger hunger: people given a ghrelin injection will pile their plates higher when turned loose on an all-you-can-eat buffet. Patients with the rare genetic disorder Prader-Willi syndrome have abnormally high levels of ghrelin and sometimes eat without ever feeling sated; some evenrupture their stomachs.
But precisely how ghrelin controls hunger was not clear because the body has several systems in place to regulate appetite, and several different hormones, including the appetite-suppressing leptin, affect hunger. “Ghrelin makes you hungry, but what does that mean?” says Michael Schwartz of the University of Washington in Seattle, who was not involved in the study. “What exactly is hunger in terms of how the brain works?”
Dagher and his colleagues enlisted the help of 20 lean, healthy volunteers. The volunteers were given a meal and then shown pictures of food three hours later, when they were neither full nor hungry. Twelve of the volunteers received injections of ghrelin.
In the brain
A brain-imaging technique called functional magnetic resonance imaging tracked blood flow in the brain while volunteers viewed the pictures. The researchers found that those who had received the ghrelin injections had more blood flow, and so more activity, in several regions of the brain.
One of these was the striatum: a reward center in the brain that contains receptors for a neurotransmitter called dopamine. Dopamine is associated with feelings of pleasure, and the striatum is also important in drug addiction.
Those who received the hormone also showed heightened activity in regions of the brain that process visual images, and in two regions — the amygdala and the orbitofrontal cortex — that coordinate responses to stimuli and strengthen memories of an event. “If you eat something that makes you sick, you will never eat it again — that’s thanks to the amygdala,” says Dagher.
The volunteers' behaviour backed up the notion that their memory was affected: when they returned the next day, those who had received ghrelin were better able to remember the pictures of food.
You must remember this
Whether ghrelin affects memory in general or only memories pertaining to food remains unknown. Studies in laboratory rats have shown that the animals' memory can be impaired when ghrelin is absent. “It’s not clear if that effect is specific for food, or if ghrelin is a general memory enhancer,” says Dagher. “If you’re a rodent, most of your memory has to do with food.”
The same may have been true for humans long ago, notes Hans-Rudolf Berthoud, a neurobiologist at Louisiana State University in Baton Rouge, who was not involved in the study. So a link between hunger and memory for our primitive ancestors makes sense. But today things are different. “To go across the street to McDonald’s doesn’t require all of that. Now we have GPS systems.”
And in modern times, the link between ghrelin and memory could impede the development of drugs that target the hormone to beat back hunger, say Dagher and his team.
Malik, S., McGlone, F., Bedrossian, D. & Dagher, A. Cell Metabolism 7, 400-409 (2008).