Genetic endowment for obesity influences learning behavior

A genetic predisposition to obesity also affects the reward system of the brain and consequently, the learning behavior

Scientists at the Max-Planck-Institute for Metabolism Research in Cologne discovered that a genetic predisposition to obesity also affects the reward system of the brain and consequently, the learning behavior: Persons with this specific gene variant showed reduced dopamine signaling-related connections as well as reduced capability to learn from negative consequences, when compared to those without disposition.

For quite a while now researchers have been searching for genes favoring obesity. In their studies they have encountered numerous suspects: “There are many genes, which are supposed to influence the weight of people. But how they do this is still unclear. And of course they also interact with each other”, explains Dr. Marc Tittgemeyer, one of the leaders of the newly published study. Only one of these genes has clear-cut data available: A change in the so-called FTO (fat mass and obesity-associated) gene has a direct effect on a person’s fat mass. Hints about any working mechanism do not exist, though. To make matters worse, scientists found evidence that FTO is additionally linked to several behavioral problems such as attention deficiency or impulse control. Experiments with mice have shown that in principal there is a neurophysiological effect of the gene: FTO clearly affected the dopamine-driven brain activity of the animals. Dopamine, often related to positive emotions, is a neurotransmitter that stimulates nerve cells in the brain. Experts suggest that it especially regulates impulse and motivation. In the present study the team of researchers around Tittgemeyer and professor Jens Brüning, director of the Max-Planck-Institute for Metabolism Research, investigated if FTO affects the human brain in terms of dopamine signaling and reward system.

The scientists recruited 79 volunteers with average-weight and the appropriate gene variants of FTO. In addition, subjects were examined on variants of the gene ANKK1. It has already been known that a particular variant of ANKK1 significantly reduced the activity of dopamine receptors. In this context Tittgemeyer emphasizes: “We wanted to examine not only the effect of FTO, but whether the two genes in combination affect neurophysiological processes”.

In a behavioral experiment the subjects were asked to choose one animal from two different animal symbols shown on a computer screen. During a training period the participants learned – based on three animal couples – that in each couple one animal is “better” than the other. In case subjects chose the correct symbol, they were rewarded with an image of a smiley face – whereas a wrong choice resulted in a sad face on the screen. In the actual test the animal symbols appeared in various combinations, and each time the subjects were asked to either choose the “good” animal or avoid the “bad”. “We wanted to examine to what extend people learn from reward or negative outcome, respectively” said Tittgemeyer. The results were obvious: People having the risk variants of both genes performed worse in avoiding the “bad” animals. These findings suggest that the two genes effectively influence the learning behavior in response to wrong decisions.

Using magnetic resonance imaging (MRI) during the test phase, the scientists monitored the blood circulation of the subject’s brains. Thereby, they could locate activated brain areas and find correlations between different regions. The research team observed that depending on gene variants the interaction of the subject`s brain areas differed: “One reason for this discovery could be a direct association of dopamine-related brain activity in such regions”, explains Tittgemeyer. That is why obesity could – at least partly – originate in the brain: “Due to a defective reward system it is difficult for some people to control their impulses. This may also affect their eating habits,” says Tittgemeyer.

The study shows that particular neurophysiological processes caused by genetic predisposition could be one of several factors explaining obesity. It supports the viewpoint that being overweight is a disorder of higher-order cognitive behavior. In other words: Even genetic causes of weight gain start in our head, but unfortunately, in an area beyond our conscious control.