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Obesity: How a weight loss drug can help with associative learning

  • Researchers report that associative learning impairments caused by obesity can be restored with liraglutide, an anti-obesity medication.
  • After just one dose, researchers said study participants with obesity showed no impairment compared to a group of non-obese participants.
  • They said that means the drug not only treats obesity by stimulating insulin production, it also can help by boosting associative learning, which in turn can improve motivation.

New research indicates that interventions aimed at curbing obesity also carry the added effect of improving the brain’s ability to learn – after just one dose.

The work was carried out by researchers at the Max Planck Institute for Metabolism Research in Cologne, Germany, and supported by funding from the University of Cologne and the University Hospital of Cologne.

The findings were published today in the journal Nature Metabolism.

Marc Tittgemeyer, a neuroscientist at the Max Planck Institute, led the study. He told Medical News Today that since the same drug used to treat obesity can also boost associative learning, it has a two-in-one effect: treating obesity directly as well as improving the neural pathways that can help people consciously lose weight.

“Interestingly, modern obesity treatment can normalize the learning of associations, thereby rendering people being susceptible again for sensory signals and, hence, being prone again to react to more subliminal interaction, such as weight-normalizing diets and conscious eating,” he explained.

Obesity and insulin sensitivity go hand-in-hand

Researchers sought to determine whether impaired insulin sensitivity – a condition common in people with weight issues in which the body’s cells fail to respond normally to insulin – could also impact dopamine function in the brain, which could in turn impair the brain’s ability to learn via sensory association.

They studied two groups: one consisting of volunteers with normal weight and high insulin sensitivity and the other consisting of people with obesity who also had reduced insulin sensitivity.

Participants were given either a placebo or the anti-obesity drug liraglutide, which functions by stimulating the production of insulin.

After just one dose of liraglutide, researchers reported that the study subjects displayed improved brain activity and associative learning. In fact, there was no discernable difference in brain activity between the subjects with more normal weight and the participants with obesity.

Obesity and the brain

Experts say the data offers insights into how obesity can alter the brain – and shows how this process can be changed with medication.

“We showed that with obesity, there are disrupted circuit mechanisms that lead to impaired learning about sensory associations,” Tittgemeyer said. “Essentially that means that information provided by sensory systems, which the brain must interpret to select a behavioral responses, are out of tune, or not balanced to homeostatic needs.”

Tittgemeyer explained that the data shows that the same neural processes that can help motivate people to get healthy can be negatively affected by obesity, creating a vicious cycle where the weight that a person is trying to lose is also disrupting their ability to motivate themselves.

“This is rather consequential for the understanding of food intake behavior, as it necessitates subconscious effects and actions translated from those that are beyond an explicit hedonic (pleasant) experience,” he said.

The next steps for the researchers will be to conduct more studies to determine the role that liraglutide plays on a molecular level. They also plan to research whether other methods of boosting insulin sensitivity – such as weight loss trials and insulin sensitizers – show a similar boost to liraglutide in terms of restoring learning impairments.

Wide range of options for treating obesity

Obesity has been on the rise for decades now, with the U.S. Centers for Disease Control and Prevention (CDC) reporting that, around the time of the beginning of the COVID-19 pandemic, more than 40 percent of adults in the United States were obese. Two decades earlier, that number stood at slightly more than 30 percent.

Early interventions for weight loss consist of the same age-old advice: watch your caloric intake, eat healthy food, and be active. Other non-invasive interventions might include cognitive behavioral therapy to refocus a person’s relationship with food.

However, if these efforts aren’t effective, the next steps might involve a doctor prescribing an anti-obesity drug. While the research conducted at the Max Planck Institute used liraglutide, there are a wide range of drugs available on the market.

Semaglutide, commonly branded as Ozempic, is – like liraglutide – an injectable GLP-1 receptor antagonist. This means that both drugs mimic natural hormones, boost insulin secretion, and improve glycemic control. While semaglutide has not been approved by the U.S. Food and Drug Administration (FDA) for weight loss, it’s been shown to be safe in clinical studies and is often used to treat diabetes.

Mir Ali, a bariatric surgeon and medical director of MemorialCare Surgical Weight Loss Center at Orange Coast Medical Center in California, told Medical News Today that while these drugs are effective when it comes to quick results, higher doses might be necessary depending on a person’s weight – and long-term success comes down to more than just the prescription.

“Weight loss can be seen immediately after beginning the medication. However, the dose is gradually increased and more weight loss occurs at higher doses,” he explained. “People can regain weight after stopping medication because they return to previous eating habits. The medication is most effective if it’s used to make long-term changes to a person’s diet. It may not ‘solve’ weight problems, as obesity is a complex issue with multifactorial contributing components.”

Whether the goal is to lose a few pounds or to drop a significant amount of weight to avoid problems down the road, Ali emphasizes the fact that many options are on the table.

“There are multiple options for weight loss: surgery is most effective for those who meet criteria, and there are also other medications besides [semaglutide] available for weight loss,” he said. “Nutritional counseling to help people change to a healthier lifestyle may also be effective for some patients, especially those who have only a modest amount of weight to lose.”

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  • Posted on August 17, 2023