Health

An Anti-obesity Medication Increases Associative Learning in Obese Adults

An Anti-obesity Medication Increases Associative Learning in Obese Adults

Obesity is a complicated disorder influenced by many factors, including genetics, lifestyle, and environmental impacts. A person’s entire health, particularly their weight and metabolic status, might influence cognitive skills such as associative learning. Improvements in obesity management, such as weight loss by medication or lifestyle modifications, may result in indirect cognitive gains, although this would need to be explored and proven through clinical trials and research.

Obesity alters energy metabolism and reduces cell insulin sensitivity. The so-called “anti-obesity drugs” are increasingly being used to treat obesity and have sparked enormous interest, particularly in the United States.

Researchers at the Max Planck Institute for Metabolism Research in Cologne, Germany, have discovered that reduced insulin sensitivity impacts sensory association learning in obese persons. A single dose of the anti-obesity medicine liraglutide was enough to restore the underlying brain circuit function and normalize these alterations.

The brain must be able to make associations in order to govern our behavior. Associating neutral external stimuli with a consequence following the stimulus (e.g., the hotplate glows red – you can burn your hand) is one example. The brain learns what the implications of our handling of the first stimulus are in this way.

These findings are extremely important. We show that basic behaviors like associative learning are affected not just by exterior environmental variables but also by the body’s metabolic status. So, whether or not a person is overweight influences how the brain learns to correlate sensory inputs and what incentive is generated.

Marc Tittgemeyer

Associative learning is the foundation for building brain connections and provides a motivating force to stimuli. It is primarily governed by a brain region known as the dopaminergic midbrain. This region has several receptors for the body’s signaling chemicals, such as insulin, and may thus adapt our behavior to our body’s physiological needs.

But what happens when the body’s insulin sensitivity decreases as a result of obesity? Is there a shift in our brain activity, our ability to learn associations, and consequently our behavior as a result of this?

Researchers at the Max Planck Institute for Metabolism Research have now measured how well the learning of associations works in participants with normal body weight (high insulin sensitivity, 30 volunteers) and in participants with obesity (reduced insulin sensitivity, 24 volunteers), and if this learning process is influenced by the anti-obesity drug liraglutide.

Low insulin sensitivity reduces the brain’s ability to associate sensory stimuli.

Anti-obesity drug improves associative learning in people with obesity

In the evening, they administered either the medicine liraglutide or a placebo to the subjects. Liraglutide is a GLP-1 agonist, which means it activates the GLP-1 receptor in the body, boosting insulin production and providing a sense of fullness. It is commonly used to treat obesity and type 2 diabetes and is administered once daily. The subjects were given a learning task the next morning that allowed the researchers to assess how well associative learning functioned. They discovered that the ability to correlate sensory inputs was less evident in obese participants than in those of normal weight and that brain activity in the areas encoding this learning tendency was diminished.

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 the brain activity to the state of normal-weight subjects.

“These findings are extremely important. We show that basic behaviors like associative learning are affected not just by exterior environmental variables but also by the body’s metabolic status. So, whether or not a person is overweight influences how the brain learns to correlate sensory inputs and what incentive is generated. The normalization we achieved with the drug in obese subjects fits with studies showing that these drugs restore a normal feeling of satiety, causing people to eat less and thus lose weight,” says study leader Marc Tittgemeyer of the Max Planck Institute for Metabolism Research.

“While it is encouraging that available drugs have a positive effect on brain activity in obese people, it is concerning that changes in brain performance occur even in young people with obesity who do not have any other medical conditions. Obesity prevention should play a far larger part in our future healthcare system. In comparison to primary prevention of obesity and associated complications, lifelong medication is the less preferred option,” says Ruth Hanßen, first author of the study and a physician at the University Hospital of Cologne.