A US study has found that “overweight people may actually find fatty or sugary food less satisfying than thin people, which leads them to overeating as a way of compensating for the relative lack of enjoyment,” reports The Independent . Those that carried a genetic variant called Taq1A1, which is associated with having fewer dopamine receptors in the pleasure centres of the brain, “seemed to have to eat more to trigger the same sort of pleasurable response as those women born with more dopamine receptors”. The newspaper also reported that those with the Taq1A1 variant were more likely to put on weight a year later.
These results will add to research looking at whether differences in brain signalling can explain why some people become obese while others do not. It is important to note that the researchers essentially carried out separate studies in the lean participants and in the overweight or obese participants, and the two groups were not compared directly. This research is in its early stages and, for now, the best way to prevent or treat overweight and obesity is by eating a healthy, balanced diet and doing regular exercise.
Where did the story come from?
Dr Eric Stice and colleagues from the Oregon Research Institute, and Universities in Oregon, Texas and Connecticut carried out this research. No sources of funding were reported for this study. It was published in the peer-reviewed journal, Science.
What kind of scientific study was this?
This was an experimental laboratory study, using an MRI brain scanner, which looked at the activity of nerve cells (neurons) in a particular part of the brain called the dorsal striatum, and related this to obesity in humans.
When people are hungry and eat, a chemical messenger called dopamine is released in the dorsal striatum, and this chemical gives people a pleasurable sensation – essentially “rewarding” them for eating. The amount of dopamine released diminishes when a person is full, and this reduces the pleasurable “reward”. Other studies have shown that blocking the effects of dopamine can lead to increased appetite and eating, and weight gain. Obese people have been shown to have fewer receptors for dopamine than lean people, and it has been suggested that this may reduce the “reward” sensation they get from food, leading to increased eating to try and get this “reward”.
In this study, the researchers used imaging techniques (functional magnetic resonance imaging or fMRI) to see whether the activity in the dorsal striatum in response to eating differed between obese and lean people. This technique measures blood flow in the different regions of the brain, and uses this as an indicator of how active they are. In addition, the researchers looked at whether activity patterns were affected by whether individuals carried a particular genetic variation (the A1 allele [form] of theTaq1A site), which is known to reduce the number of dopamine receptors, and increase the risk of obesity.
The researchers excluded anyone who reported binge eating or compensatory behaviours (such as vomiting for weight control) in the past three months. They also excluded those who used psychotropic medications or illicit drugs, who had experienced head injury with a loss of consciousness or had a current major psychiatric disorder.
In their first experiment, the researchers enrolled 43 overweight and obese female college students (average body mass index [BMI] 28.6, average age 20 years) who were taking part in a weight loss trial. They asked the volunteers not to eat for 4-6 hours before the experiment. They then used fMRI to scan the brains of the volunteers while they looked at pictures of either a chocolate milkshake or a glass of water for two seconds, followed by drinking either a chocolate milkshake or a tasteless solution, or no drink for five seconds. The drinks were delivered by syringe to control the volume and speed of drinking. The order in which the participant saw the picture and then received the drinks was randomised. This experiment was repeated on the individual 20 times.
In the second experiment, the researchers enrolled 33 healthy teenage girls who were lean to obese (average BMI 24.3, average age 15.7 years), and were taking part in a trial looking at preventing eating disorders. This experiment was similar to the first, but the pictures used were geometric shapes rather than pictures of a milkshake or glass of water.
The researchers looked at the activity of the dorsal striatum during these experiments to see if there were changes in activity, depending on which picture was presented and which drink was received. They also looked at whether these differences could predict how the women’s BMI changed over the year of follow-up. These analyses took into account BMI at the start of the study, the presence or absence of the A1 allele, and normal dorsal striatal activation. Volunteers from both experiments were followed up for a year, and their body mass index (BMI) was measured at the end of this time.
What were the results of the study?
The researchers found that women with a higher BMI showed less increase in activity in their dorsal striatum in response to the milkshake when compared with the tasteless solution. They found that the relationship between BMI and striatal activity was stronger in women who carried an A1 allele than in those who didn't.
In the second experiment, the women’s BMI increased an average of 3.63% over the year of follow-up. The researchers found that lean volunteers who did not have an A1 allele and who showed greater activation in the dorsal striatum in response to the milkshake, had the greatest increase in BMI during follow-up. They also found similar results among overweight and obese participants without an A1 allele.
There was no significant relationship between dorsal striatum activation and BMI increase in overweight and obese volunteers who did have the A1 allele. However, among lean participants with an A1 allele, the larger the activation in the dorsal striatum in response to the milkshake, the less the increase in BMI during follow-up.
What interpretations did the researchers draw from these results?
The researchers conclude that their results show that people whose dorsal striata are less responsive to food intake are at greater risk of obesity, particularly those whose genes predispose them to reduced dopamine signalling. They suggest that behavioural or drug treatments that reverse this lack of responsiveness may help to prevent and treat obesity.
What does the NHS Knowledge Service make of this study?
This study gives some indication of activity in the dorsal striatum in relation to food intake in people with different BMIs. There are a number of points to consider when interpreting this study:
- It is important to note that the researchers essentially carried out separate studies in the lean participants and those who were overweight or obese, and the two groups were not compared directly. The experiments performed in overweight and obese individuals and lean individuals differed slightly (in pictures used), and this may have affected the results.
- The technique used does not directly measure dopamine signalling, and therefore the effects seen cannot be proven to be caused by reduced dopamine signalling.
- The authors acknowledge that the reduced striatal response may be due to changes in dopamine signalling occurring naturally in overweight and obese people, or it may be due changes caused by overeating. This experiment cannot prove which.
- The study was relatively small, and it studied brain activity under controlled experimental conditions. It is not clear how well this would reflect what happens in the brain in real life in response to food and drink.
- This study included healthy young women only, and the results may not apply to men, older age groups, or those who are less healthy (e.g. those with eating disorders).
- Only about half of the lean volunteers (17 out of 33) were followed up for a year, therefore the loss of such a high proportion of people to follow up may have affected results. It is also unclear whether the increase in BMI seen during follow-up would lead to these women being classified as overweight or obese.
These results contribute to a body of research looking at whether differences in brain signalling can explain why some people become obese while others do not. This research is in its early stages, and for now, the best way to prevent or treat overweight and obesity is by eating a healthy, balanced diet with an appropriate number of calories, and engaging in physical activity.
Analysis by Bazian
Edited by NHS Website
Links to the headlines
New Scientist, 17 October 2008
BBC News, 17 October 2008
The Independent, 17 October 2008
The Daily Telegraph, 17 October 2008
Daily Mail, 17 October 2008
Links to the science
Cochrane Database Syst Rev 2005, Issue 2
Cochrane Database Syst Rev 2006, Issue 4
Science 2008; 322: 449-452