What sparked your research into brain chemistry and eating habits?
Several times every day, we choose when, where, what, with whom, and how much to eat. Many of these eating decisions have become automatic and don’t require cognitive effort.
In other words, many of our eating habits were formed as a result of past eating occasions that have been repeated over and over.
Eating habits are associated with both internal cues, like hunger, as well as a variety of external cues like watching TV, experiencing a stressful situation, or viewing food advertisements.
Over the past few decades, our food environment has changed dramatically such that we are now inundated with cues to consume convenient, inexpensive, palatable, energy-dense food.
I want to understand why some people may be more susceptible to these environmental cues such that they overeat and develop obesity. So, in this study we investigated whether dopamine receptor binding in brain regions known to mediate habit formation is related to obesity.
In particular, perhaps dopamine signalling in these brain regions might be responsible for the fact that people with obesity often report that their eating behaviour is particularly susceptible to environmental cues. This phenomenon is called opportunistic eating and was measured using a detailed questionnaire.
Please can you give a brief overview of dopamine and the role it plays in the habit-forming region of the brain?
Dopamine plays a central role in learning about environmental cues that predict food reward and forming automated habitual eating behaviours based on repeated past eating episodes.
We know from animal experiments that dopamine signalling in a region of the brain called the dorsolateral striatum mediates habit formation and increased dopamine accelerates the development of habit formation from previously goal-directed behaviours.
Furthermore, suppressing dopamine signalling specifically in the dorsolateral striatum prevents habit formation and can even reverse previously developed habits.
Were you surprised to find greater dopamine activity in obese research participants than in leaner counterparts?
We were somewhat surprised by our results since they initially appeared to contrast with a previous theory about how dopamine might be involved in obesity.
Specifically, the reward-hypofunction theory of obesity suggests that dopamine’s role in encoding food reward might be altered in people with obesity such that they have to consume more food to achieve the same level of reward as a person without obesity.
The basis of this model comes from the field of drug addiction where striatal dopamine receptors have been shown to be lower in drug addicts who require more of the drug to experience the same degree of pleasure.
A highly-cited study published in The Lancet in 2001 compared dopamine receptor binding in 10 people with severe obesity to 10 normal and slightly overweight people and showed that the people with severe obesity had reduced dopamine receptor binding that was similar to that of drug addicts.
We thought that our study would replicate this previous finding in a larger number of subjects that had a continuous range of body fat, from the lower end of normal weight to severe obesity.
We also had much greater control of the behaviour of our study participants since they were confined to the metabolic ward at the NIH Clinical Center where they were fed a balanced diet for at least one full day before morning PET scans that followed 3 hours after a standardized breakfast.
Finally, we used a dopamine receptor tracer that is less susceptible to past food intake than the tracer used in the previous study that has been shown to be influenced by recent eating.
To our surprise, we found somewhat different results with increased dopamine binding in the dorsolateral striatum in people with obesity and increased opportunistic eating behaviour.
So, rather than reward-hypofunction, our results emphasized dopamine’s role in habit formation as playing a potentially important role in eating behaviour and obesity.
What did your research suggest about the region of the brain controlling reward in the individuals you studied?
The main brain region responsible for dopamine’s role in encoding reward and motivation is called the nucleus accumbens which is part of the ventromedial striatum.
We found no significant changes in dopamine receptor binding in the accumbens region in people with obesity which appears to conflict with the reward hypo-function theory of obesity.
However, we did find regions of the ventromedial striatum where dopamine binding was negatively correlated with adiposity. In other words, there was a part of the ventromedial striatum, including a portion of the nucleus accumbens, that appeared to lend some support to the reward hypo-function theory of obesity. Therefore, eating behaviour may be more habitual and less rewarding in people with obesity.
Did your research distinguish whether obesity is a cause or an effect of these brain patterns?
Our study did not demonstrate a causal relationship. Rather, we found significant correlations between dopamine receptor binding, opportunistic eating behaviour, and body fat at only one point in time.
From these data, we cannot tell if the dopamine activity patterns were caused by the eating behaviour and development of obesity or whether the dopamine activity differences caused changes in eating behaviour and obesity.
What further research is needed to demonstrate cause and effect among habit formation, reward, dopamine activity, eating behaviour and obesity?
We will need to investigate how changes in eating behaviour and body fat alter dopamine activity patterns over time.
We also need to examine how changes in dopamine receptor binding patterns over time manifest in actual behaviour changes, especially with regard to eating.
What impact do you think your research will have?
I hope that our research will help us better understand why some people are more susceptible than others to the development of obesity and the role that the food environment has in this process.
I also hope that our research helps to show that obesity is a complex problem that may not be as easily solved by repeated advice to eat less and exercise more.
Rather, despite our short-term ability to change eating behaviour through will-power, there may be strong drivers to return to old habits that have a neurobiological basis.
Where can readers find more information?
Our research on dopamine receptor binding patterns in obesity was published in the journal Molecular Psychiatry:
J. Guo, W.K. Simmons, P. Herscovitch, A. Martin, and K.D. Hall. ‘Striatal dopamine D2-like receptor correlation patterns with human obesity and opportunistic eating behavior.’ Molecular Psychiatry 19(10):1078-1084 (2014).
About Dr Kevin Hall
Dr. Kevin Hall is a tenured Senior Investigator at the National Institute of Diabetes & Digestive & Kidney Diseases, one of the National Institutes of Health in Bethesda MD, where his main research interests are the determinants of food intake, macronutrient metabolism, energy balance, and body weight.
Dr. Hall’s laboratory performs experiments in humans and rodents and develops mathematical models and computer simulations to help design, predict, and interpret the experimental data.
Dr. Hall is the recipient of the NIH Director’s Award, the NIDDK Director’s Award, the Lilly Scientific Achievement Award from The Obesity Society, the Guyton Award for Excellence in Integrative Physiology from the American Society of Physiology, and his award-winning Body Weight Simulator (http://bwsimulator.niddk.nih.gov) has been used by more than a million people to help predict how diet and physical activity dynamically interact to affect human body weight.
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