Study: Anti-Obesity Medication Normalizes Sensory Learning for Those With Obesity

Liraglutide, an anti-obesity medication, helped to normalize sensory-associated learning and helped restore brain circuit function in those who have obesity and have reduced sensitivity to insulin, according to results of a study published in Nature Metabolism.¹

Associative learning develops using sensory information that alerts individuals to a changing environment, directing and informing decisions. One such change can come from the regulation of energy balance, such as an individual’s need to eat, which is stimulated by metabolic signals to the brain. Dopamine neurons play a crucial role in adaptive learning, according to the study authors, who said that these neurons are particularly susceptible to the nutritional value of foods.¹

Image credit: MP Studio - stock.adobe.com

“We show here that basic behaviors such as associative learning depend not only on external environmental conditions but also on the body's metabolic state. So, whether someone has overweight or not, also determines how the brain learns to associate sensory signals and what motivation is generated. The normalization 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," Marc Tittgemeyer, PhD, from the Max Planck Institute for Metabolism Research, said in a statement.²

In the study, investigators measured the learning associations for 30 individuals who had high insulin sensitivity and a lean body weight, according to the study guidelines, and for 24 individuals with obesity and reduced insulin sensitivity. They aimed to determine whether liraglutide could impact the learning process for individuals who had reduced insulin sensitivity.^1,2

According to the study authors, individuals completed sensory associative learning tasks, including 1 that measured auditory cues and 1 that assessed visual cues, during functional magnetic resonance imaging on 2 different days. Participants received liraglutide on the first day and the placebo on the second.¹

Investigators found that although liraglutide helped improve the learning rate for those with impaired insulin sensitivity, it also reduced the learning rate in the group who had normal insulin sensitivity. The results showed an effect nearly twice as large for the impaired sensitivity group compared with the normal sensitivity group.¹

The study investigators noted that the difference in sensory learning after administration of liraglutide was non-existent in the 2 groups.^1,2

"While it is encouraging that available drugs have a positive effect on brain activity in obesity, it is alarming that changes in brain performance occur even in young people with obesity without other medical conditions. Obesity prevention should play a much greater role in our health care system in the future. Lifelong medication is the less preferred option in comparison primary prevention of obesity and associated complications," Ruth Hanssen, MD, a physician at the University Hospital of Cologne, said in the press release.²

Although the data is comparable with previous animal data, investigators said there are limitations of the study. These include the molecular mechanisms and central access routes for liraglutide, which they state remain speculative in humans. They added that the effects cannot be definitively attributed to liraglutide as there are overlapping effects of both liraglutide and insulin.¹

References

1. Hanssen R, Rigoux L, Kuzmanovic B, Iglesias S, et al. Liraglutide restores impaired associative learning in individuals with obesity. Nat Metab. 2023;10.1038/s42255-023-00859-y. doi:10.1038/s42255-023-00859-y

2. Anti-obesity drug improves associative learning in people with obesity. News release. Science Daily. August 17, 2023. Accessed August 21, 2023. https://www.sciencedaily.com/releases/2023/08/230817163920.htm