28 Aug 2023
Max Planck Institute for Metabolism Research finds anti-obesity drugs restore normal brain function and reboot people's relationship with food
BY Tom Walker
Drugs that help normalise insulin sensitivity to reduce body fat in people suffering from obesity can improve learning outcomes.
Researchers at the Max Planck Institute for Metabolism Research in Cologne, Germany, looked at how the drug Liraglutide – a medication used to treat Type 2 diabetes and chronic obesity – could benefit brain activity.
To control our behaviour, the brain must be able to form associations – for example, children learn quickly that if a fire glows red, they can burn their hand if they touch it.
This seemingly simple learning pattern involves associating a external neutral stimulus (fire) with a consequence (pain). It also applies to our relationship with food and the feeling of fullness/satiety that follows eating.
Associative learning is essentially controlled by a brain region called the dopaminergic midbrain. This region has many receptors for the body's signalling molecules – such as insulin – and can thus adapt our behaviour to the physiological needs of our body.
The Max Planck team set out to find out what happens when the body's insulin sensitivity is reduced due to obesity. The aim was to see whether it would change brain activity and the ability to learn associations and thus alter behaviour.
The researchers measured how well the learning of associations works in participants with normal body weight (30 volunteers with high insulin sensitivity) and in participants with obesity (24 volunteers with reduced insulin sensitivity) and if this learning process is influenced by taking Liraglutide.
They did this by injecting the participants with either the drug or a placebo in the evening. Liraglutide is a GLP-1 agonist, which activates the GLP-1 receptor in the body, stimulating insulin production and producing a feeling of satiety. It's given once a day.
The next morning, the subjects were given a learning task that allowed the researchers to measure how well associative learning works.
They found that the ability to associate sensory stimuli was less pronounced in participants with obesity than in those of normal weight and that brain activity was reduced in the areas encoding this learning behaviour.
After just one dose of Liraglutide, participants with obesity no longer showed these impairments and no difference in brain activity was seen between participants with normal weight and obesity.
In other words, the drug returned brain activity to the state of normal-weight subjects.
Study leader Marc Tittgemeyer from the Max Planck Institute, said: "These findings are of fundamental importance.
"We show that basic behaviours, such as associative learning, depend not only on external environmental conditions, but also on the body’s metabolic state.
"Whether someone is overweight or not also determines how the brain learns to associate sensory signals and what motivation is generated from these signals.
"The normalisation we achieved with the drug in subjects with obesity, therefore, fits with studies showing that these drugs restore a normal feeling of satiety, causing people to eat less and therefore lose weight."
The study was published in the journal Nature and the full research paper can be found here.
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