LIRAGLUTIDE RESTORES BRAIN

Obesity changes the way the body handles energy and makes cells less responsive to insulin. Medications known as "anti-obesity drugs" are being used more frequently to address obesity, drawing significant attention in the United States. 

Researchers at the Max Planck Institute for Metabolism Research in Cologne, Germany, have demonstrated that, in people with obesity, reduced insulin sensitivity impairs the brain's ability to learn sensory associations. Remarkably, a single dose of the anti-obesity medication liraglutide was able to reverse these effects and restore normal brain circuit function.

For us to regulate our actions, the brain needs to form associations, such as connecting a neutral stimulus with its outcome—think of recognizing that a glowing red hotplate can burn your hand. This process, called associative learning, is critical for building neural connections and motivating behavior. It's controlled mainly by the dopaminergic midbrain, a region rich in receptors for signaling molecules like insulin. This allows the brain to adjust behaviors based on the body's physiological needs.

When obesity causes insulin sensitivity to drop, researchers wanted to know: Does this alter brain function, learning ability, and behavior? To find out, they compared how well people with average weight (and higher insulin sensitivity, 30 participants) and people with obesity (and lower insulin sensitivity, 24 participants) performed at associative learning, and whether liraglutide had any impact.

They found that low insulin sensitivity hindered the brain's capacity to connect sensory cues. The evening before testing, participants received either liraglutide or a placebo. Liraglutide is a GLP-1 agonist that stimulates GLP-1 receptors, promoting insulin release and feelings of fullness. It's commonly prescribed for obesity and type 2 diabetes and is taken daily. The next morning, participants completed a learning task designed to measure associative learning. Results showed that those with obesity performed worse at forming associations and had reduced brain activity in regions related to this learning.

After just one dose of liraglutide, these deficits disappeared: participants with obesity showed no difference in learning ability or brain activity compared to those of average weight. The drug essentially restored brain function to typical levels.

"These findings are fundamental," says study leader Marc Tittgemeyer. "We show that basic behaviors like associative learning depend not just on external factors but also on the body's metabolic state. Whether someone is overweight affects how the brain learns from sensory signals and what motivates them. The improvement we saw with the drug aligns with previous studies showing that these medications help restore normal feelings of fullness, which leads to eating less and weight loss."

Ruth Hanßen, the study's first author and a physician at the University Hospital of Cologne, adds: "While it's promising that existing drugs can improve brain activity in people with obesity, it's concerning that such changes in brain performance appear even in young individuals with obesity who don't have other health problems. Preventing obesity should become a much higher priority in healthcare. Lifelong medication is not as desirable as effective prevention of obesity and its complications."

This study was conducted at the Max Planck Institute for Metabolism Research, with support from the CECAD Cluster of Excellence for Ageing Research at the University of Cologne and the University Hospital of Cologne.