It sounds counterintuitive. But scientists who watched young women savor milkshakes inside a brain scanner concluded that when the brain doesn't sense enough gratification from food, people may overeat to compensate.
The small but first-of-a-kind study even could predict who would pile on pounds during the next year: Those who harbored a gene that made their brain's yum factor even more sluggish.
"The more blunted your response to the milkshake taste, the more likely you are to gain weight," said Dr. Eric Stice, a senior scientist at the Oregon Research Institute who led the work, published in Friday's edition of the journal Science.
A healthy diet and plenty of exercise are the main factors in whether someone is overweight. But scientists have long known that genetics also play a major role in obesity - and one big culprit is thought to be dopamine, the brain chemical that's key to sensing pleasure.
Eating can temporarily boost dopamine levels. Previous brain scans have suggested that the obese have fewer dopamine receptors in their brains than lean people. And a particular gene version, called Taq1A1, is linked to fewer dopamine receptors.
"This paper takes it one step farther," said Dr. Nora Volkow of the National Institutes of Health, a dopamine specialist who has long studied the obesity link. "It takes the gene associated with greater vulnerability for obesity and asks the question why. What is it doing to the way the brain is functioning that would make a person more vulnerable to compulsively eat food and become obese?"I
t's "very elegant work," she added.
First, Stice's team had to figure out how to study the brain's immediate reactions to food. Moving inside an MRI machine skews its measurements, which ruled out letting the women slurp up the milkshakes. Yale University neuroscientist Dana Small solved that problem, with a special syringe that would squirt a small amount of milkshake or, for comparison, a tasteless solution into the mouth without study participants moving. They were told when to swallow, so researchers could coordinate the scans with that small motion.
Then they recruited volunteers, 43 female college students ages 18 to 22 and 33 teenagers, ages 14 to 18. Body mass index calculations showed the young women spanned the range from very skinny to obese.
Brain scanning showed that a key region called the dorsal striatum - a dopamine-rich pleasure center - became active when they tasted the milkshake, but not when they tasted the comparison liquid that just mimicked saliva.
Yet that brain region was far less active in overweight people than in lean people, and in those who carry that A1 gene variant, the researchers reported. Moreover, women with that gene version were more likely to gain weight over the coming year.
It's a small study with few gene carriers, and thus must be verified, Volkow stressed.
Still, it could have important implications. Volkow, who heads NIH's National Institute of Drug Abuse, notes that "dopamine is not just about pleasure." It also plays a role in conditioning - dopamine levels affect drug addiction - and the ability to control impulses.
She wonders if instead of overeating to compensate for the lack of pleasure - Stice's conclusion - the study really might show that these people with malfunctioning dopamine in fact eat because they're impulsive.
Regardless, most people's tongues find a milkshake quite tasty; the brain reaction is subconscious.
But if doctors could determine who carries the at-risk gene, children especially could be steered toward "recreational sports or other things that give them satisfaction and pleasure and dopamine that aren't food ... and not get their brains used to having crappy food," said Stice, a clinical psychologist who has long studied obesity.
"Don't get your brain used to it," he said of non-nutritious food. "I would not buy Ho Hos for lunch every day because the more you eat, the more you crave."