Brain Reward System Underactive In Some Overweight People

Dr. Agatha van der Klaauw, PhD Wellcome Trust Postdoctoral Clinical Fellow Wellcome Trust-MRC Institute of Metabolic Science University of Cambridge Metabolic Research Laboratories Addenbrooke's Hospital Cambridge, United Interview with:
Dr. Agatha van der Klaauw, PhD
Wellcome Trust Postdoctoral Clinical Fellow
Wellcome Trust-MRC Institute of Metabolic Science
University of Cambridge Metabolic Research Laboratories
Addenbrooke’s Hospital
Cambridge, United Kingdom


Medical Research: What are the main findings of the study?

Dr. van der Klaauw: Obesity occurs when we eat more calories than we burn which is often easy to do as many foods are highly palatable and high in calories. Highly palatable foods such as chocolate trigger signals in the brain that give a feeling of pleasure and reward (sometimes called cravings) which can contribute to overeating. These signals are processed in the reward centres in the brain, where sets of neurons release chemicals such as dopamine. However, very little is known about whether the reward centres of the brain work differently in some people who are overweight.

In this study, we were interested in studying overweight people who had a problem with the melanocortin 4 receptor (MC4R) gene. About 1% of obese people have a problem in this gene which contributes to weight gain from a young age. We compared three groups of people: people who were overweight due to a problem in the MC4R gene, people who were overweight but the gene was normal and some people who were normal weight. We performed functional Magnetic Resonance Imaging (fMRI) scans to look at how the reward centres in the brain were activated by pictures of appetizing food such as chocolate cake compared to bland food such as rice or broccoli and non-food items such as staplers.

We found that in normal weight people, the reward centres are activated (light up) when they are shown pictures of cake or chocolate and the same was seen in overweight people with a problem in the MC4R gene. But we found that the reward centres were underactive in overweight volunteers (in whom the gene was normal).

Medical Research: Were any of the findings unexpected?

Dr. van der Klaauw:  This is actually the first study looking reward centre activation in people who have a problem with the MC4R gene. We knew from our previous studies in people with a lack of the hormone leptin, which initiates pathways in the brain that involves the MC4R, that the reward centres are regulated by leptin.  Also, several studies have shown before that the reward centres might become underactive when you gain weight. However, now we showed a completely different response different response in two groups of people of the same age and weight with and without a gene problem. This tells us the MC4R is involved in the reward pathways in the brain.

Medical Research: What should clinicians and patients take away from your report?

Dr. van der Klaauw:  Up until now, we did not know the biological processes that are associated with the reward system being underactive in some overweight people. This study shows that the MC4R pathway is involved. Understanding this pathway may help in developing interventions to limit the overconsumption of highly palatable foods that can lead to weight gain.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. van der Klaauw:  We are continuing to study the pathways in the brain that coordinate the need to eat and the reward and pleasure from eating, work which is important in finding a way to limit overconsumption of palatable foods and reduce the burden of obesity.

Obesity Associated Melanocortin-4 Receptor Mutations are Associated with Changes in the Brain Response to Food Cues
an der Klaauw AA1, von dem Hagen EA, Keogh JM, Henning E, O’Rahilly S, Lawrence AD, Calder AJ, Farooqi IS.

J Clin Endocrinol Metab. 2014 Jul 25:jc20141651. [Epub ahead of print


Last Updated on July 31, 2014 by Marie Benz MD FAAD