Obesity and Cognitive Function: How Liraglutide’s Impact Offers Hope

Summary: Obesity affects how the body uses energy and decreases the sensitivity of cells to insulin. The term “anti-obesity drugs” is gaining increasing usage for the treatment of obesity, attracting significant attention, particularly in the USA. Researchers have recently established that decreased insulin sensitivity in obese individuals has an impact on the learning of sensory associations. Just one dose of the anti-obesity medication liraglutide might normalize these alterations and restore the underlying brain circuit function.

Source: Max Planck Institute for Biology of Aging

Liraglutide improves cognitive function in people suffering obesity

The brain needs to be able to create associations in order to govern our conduct. This entails, for instance, linking a neutral external stimulus with a result occurring after the stimulus (for instance, the hotplate flashes red—you could burn your hand). The brain gains knowledge of the implications of how we respond to the initial stimulus in this way. The foundation for creating brain connections and the source of the motivational power in stimuli is associative learning. The dopaminergic midbrain, a part of the brain, is largely in charge of controlling it. Since this area includes a large number of receptors for the body’s signalling molecules, including insulin, it can modify our behaviour to meet physiological requirements.

But what occurs when obesity reduces the body’s sensitivity to insulin? Does this alter our brain activity, capacity for association learning, and hence, behaviour? Now, scientists at the Max Planck Institute for Metabolism Research have examined how well the learning of associations functions in individuals with normal body weight (high insulin sensitivity, 30 volunteers) and in individuals with obesity (reduced insulin sensitivity, 24 volunteers), as well as whether the anti-obesity medication liraglutide affects this learning process.

The brain’s capacity to link sensory stimuli is diminished by low insulin sensitivity in people suffering from obesity.

During the study, participants were administered either an evening trial injection of the medication liraglutide or a placebo. A substance known as a GLP-1 agonist, liraglutide activates the GLP-1 receptor in the body, increasing insulin levels and causing satiety. Administered once a day and often utilized to treat type 2 diabetes and obesity, it was followed by a learning exercise the next morning for participants. This exercise enabled researchers to assess the efficacy of associative learning. The study revealed that the ability to link sensory stimuli was less pronounced in obese individuals compared to participants with normal weight. Furthermore, brain activity in the regions encoding this learning behavior experienced a decrease.

Participants with obesity no longer displayed these abnormalities after just one dosage of liraglutide, and there was no distinction in brain activity between participants with normal weight and obesity. In other words, the medication brought brain activity back to that of people who were of a normal weight.

Conclusion

“These discoveries are critically important. Here, we demonstrate how basic behaviours like associative learning are influenced by both internal metabolic state and exterior environmental factors. Therefore, whether a person is overweight or not also affects how their brain develops associations between sensory input and motivation. According to studies showing that these medications restore a normal feeling of satiety, causing people to eat less and consequently lose weight, the normalisation we achieved with the drug in obese subjects fits with this finding, says study leader Marc Tittgemeyer from the Max Planck Institute for Metabolism Research.

Although it’s positive that current medications demonstrate beneficial effects on the brain activity of people with obesity, it’s worrisome that alterations in brain function can emerge even among younger individuals with obesity who do not have any other underlying medical issues. Future healthcare reforms should place considerably more emphasis on preventing obesity. According to Ruth Hanßen, MD, first author of the study and a physician at the University Hospital of Cologne, lifelong medication is the less desirable alternative in comparison to primary prevention of obesity and associated consequences.