Obesity research at Brookhaven

The lower PET scan images, labeled GDP, show glucose metabolism in the brains of obese and control (comparison) subjects. There are no differences. The upper PET scans show where the radiotracer C-11 raclopride binds to dopamine receptors. These images show that obese subjects have fewer dopamine receptors than control subjects.

Recent studies reveal that more than 50 percent of Americans are overweight and 25 percent are obese, conditions with many long-term health effects and few effective treatments. The growth of this major public-health problem adds urgency to scientists' efforts to understand the mechanisms underlying pathological overeating. Though obesity is the product of many interacting variables, there is mounting evidence that the motivation and reward circuits regulated by dopamine play a role.

This makes intuitive sense because eating, like other activities regulated by dopamine reward circuits, is a highly reinforcing behavior. The behavior of overeating in obese subjects shares similarities with the compulsive use of drugs in addicted subjects.

To assess the involvement of brain dopamine in normal and pathological food intake in humans, we use positron emission tomography (PET), a method by which we can measure brain dopamine and dopamine receptor levels across subjects under varying conditions.

One of our most recent publications shows that smelling, seeing, and talking about food -- even without the pleasure of its consumption -- increases brain dopamine in non-obese, food-deprived subjects. This provides evidence of an involvement of dopamine in the motivational behaviors that drive food intake, independent of the pleasure of eating the food.

This finding builds upon research we published last year, which showed that pathologically obese subjects had fewer brain dopamine D2 receptors than normal-weight subjects, and that D2 levels were inversely associated with the subjects' body mass index. The finding of lower dopamine D2 receptor levels in obese individuals is similar to what PET studies have found in drug addicts. Lower D2 receptors in obese individuals would make them less sensitive to reward stimuli, which in turn would make them more vulnerable to food intake as a means to temporarily compensate for this deficit.

Another article, published June 19, shows enhanced activity in the brain regions involved with sensory processing of food in obese subjects. This enhanced sensitivity is likely to increase the rewarding properties of food and could account for the powerful salience that food has in obese individuals.

Together these PET studies show that the dopamine system is involved in the rewarding (hedonic) as well as the non-rewarding motivational properties of food that regulate eating behaviors in humans. These findings encourage us to further evaluate overeating disorders from the perspective of dopamine dysfunction and to seek better treatments for this major public health problem.

by Gene-Jack Wang, Medical Department, BNL