The Pleasure Factor

It was a difficult question for obesity researchers: do some people overeat because they find eating more pleasurable or gratifying than others? Logically, that makes a lot of sense—it's a time-tested principle of psychology: if a behavior feels good, we'll keep doing it. But a new study published today in the journal Science adds to a growing body of research suggesting the opposite: that women who derive less pleasure from eating may eat more to compensate, putting them at higher risk for weight gain and obesity. The research also discovered a particular genetic trait that, when present, is associated with an even stronger relationship between low sense of reward and overeating.

"If you ask overweight individuals if they crave food, I really think they are legitimately thinking it's more rewarding," says study author Eric Stice, a senior scientist at the Oregon Research Institute. "They'll say they're really sensitive to the rewards. But when you look at the brain scans you get a different picture."

Previous brain imaging studies have looked at what happens when we look at pictures of food. In those cases, obese individuals tend to anticipate a higher level of satisfaction of eating the pictured food than lean individuals do, supporting the idea that the people who overeat are the ones who find it more rewarding. But the Science study was the first to do those same fMRI scans while participants were actually eating—or, in this case, drinking a chocolate milkshake. "Nobody had ever administered food to people in a brain scanner and looked at what happens in the brain while you're eating," says Stice. "Now we have evidence that, when you give an obese individual a chocolate milkshake, there's less of a response going on."

What they found had a lot to do with dopamine, a neurotransmitter typically released in response to a pleasurable experience. Using an fMRI machine, the researchers measured the activity in an area of the brain that tends to be a hub for dopamine, called the dorsal striatum, when women had either a pleasurable food (the chocolate milkshake) or a control food (a tasteless solution). Obese women showed less activity in that region of the brain when they drank the milkshake compared to their leaner counterparts. And when researchers followed up with their participants a year later, they found those with decreased activity were also more likely to have gained weight. The more an individual overeats, the less potent the rewards from eating become and that creates a pattern of overeating. "The new bit is that once you start down that obesity track, it's hard to get back off," says Stice.

That risk was particularly pronounced among individuals with a particular genetic variation known as the Taq1A1 allele, suggesting a genetic disposition for weight gain—what other researchers call the most significant finding of this study. "What this research does to move things forward is identify a genetic component to brain functioning in obese people," says Gene-Jack Wang, a scientist with the Brookhaven National Laboratory. "This is a gene that can go any direction and these people are potentially more vulnerable [to having lower levels of dopamine]."

The study results reinforce the notion of obesity as similar to drug addiction, a comparison that researchers have been toying around with for the past few years. Dopamine has played a critical role in addiction research, where researchers have seen a similar pattern. "This research follows what we have seen in addictive people," says Nora Volkow, director of the National Institute on Drug Abuse. "At first we thought they were more sensitive to pleasurable responses. But research has shown exactly the opposite, that they have a blunted response to drugs and release much less dopamine. With obesity, it took everyone by surprise."

Researchers know that these findings of a genetic basis for low-reward overeating are important, but there's still a lingering question: how this research can best translate into obesity-prevention efforts. "A lot of things come out of this, a lot about future applications, possible drug treatments," says Wang. "It provides answers, but is also a bit of another Pandora's box." Wang and others know genetics is definitely not everything—rates of obesity have skyrocketed in the past century, far too quickly to be attributable to genetic variation alone—and that our nutritional environment plays an extremely significant role.

Still, if doctors can pinpoint genetic risk factors for obesity, it could reshape treatment: by, for example, identifying high-risk individuals early on or using pharmacologic interventions that could counterbalance low dopamine levels. Stice says he's not an advocate of genotyping, which he says would be "infeasible." Instead, he sees the main message of his study as a public-health warning, a strong reminder of why it's important to avoid overeating in the first place. "The more you eat, the less reward you get and the worse the problem is going to get," says Stice. Talk about a no-win situation.

© 2008