Weight loss connected to nerve cells in the brain, study finds

A popular weight-loss drug may be changing how doctors treat obesity—but scientists are just starting to uncover exactly how it works inside the brain. A group of researchers from the University of Gothenburg in Sweden recently uncovered how a small, specific group of brain cells could explain semaglutide’s powerful effects on appetite and body fat—with fewer side effects like nausea and muscle loss.

This discovery not only offers fresh insight into how semaglutide helps people lose weight but also points the way to developing even better treatments. Instead of triggering both the helpful and harmful effects at once, new drugs might one day target just the neurons responsible for reducing hunger and burning fat—while avoiding the ones tied to discomfort.

Semaglutide belongs to a class of drugs known as GLP-1 receptor agonists. These were originally designed to treat type 2 diabetes. But over time, doctors noticed that many patients lost weight while taking the medication. This led to the approval of semaglutide for treating obesity under brand names like Ozempic and Wegovy.

In large clinical trials, people taking semaglutide lost about 15% of their body weight over 68 weeks. That’s more than most other weight-loss drugs on the market. Yet many patients experience side effects, including nausea. And some studies have raised concerns about the drug reducing lean muscle mass, which could become a problem for older adults.

Scientists already knew that semaglutide lowers blood sugar by acting directly on the pancreas. But when it comes to weight loss, the brain plays the main role. Even though semaglutide doesn’t easily cross the blood-brain barrier, it collects in certain brain regions that don’t have one—especially an area called the dorsal vagal complex, or DVC.

This part of the brainstem includes two key areas: the area postrema and the nucleus of the solitary tract. Both are known to influence appetite, digestion, and metabolism. When semaglutide reaches this region, it activates brain cells that reduce hunger and body weight. But the details of that process have remained unclear—until now.

To better understand which brain cells were responsible for semaglutide’s effects, researchers at the Sahlgrenska Academy tracked how the drug affected mice. After semaglutide was injected, they looked for brain cells that became active. They found that many of these cells in the area postrema and the nucleus of the solitary tract expressed a gene called Adcyap1. This gene produces a neuropeptide called PACAP (pituitary adenylate cyclase-activating polypeptide), which is known to influence appetite and metabolism.

To test whether these Adcyap1-positive neurons were truly responsible for semaglutide’s effects, the team used advanced tools to stimulate them directly—without using the drug. When activated, these neurons caused the mice to eat less and lose weight. Importantly, they burned fat rather than muscle, and showed only minor signs of nausea.

The researchers then went a step further. They destroyed these neurons in a group of mice and gave them semaglutide. As a result, the drug’s impact on appetite and fat loss dropped significantly, while the side effects remained. This confirmed that the Adcyap1-positive neurons in the DVC were crucial for the drug’s positive outcomes—but not its unwanted ones.

“This suggests that these nerve cells control the beneficial effects of semaglutide,” said Júlia Teixidor-Deulofeu, the study’s lead author and a PhD student at the University of Gothenburg. “We have therefore identified a specific group of nerve cells that is necessary for the effects that semaglutide has on weight and appetite, but which does not appear to contribute to any significant extent to side effects such as nausea.”

One reason this discovery is so important is because it could help drug developers design more precise treatments. By focusing only on the nerve cells that reduce appetite and burn fat, future medications could provide weight loss benefits without the drawbacks of nausea or muscle loss.

That’s especially relevant for people who already have lower muscle mass, such as older adults. Losing more lean tissue can lead to problems like frailty or even sarcopenia, a condition marked by extreme muscle wasting.

The new study also offers insight into the wider role of the dorsal vagal complex in controlling energy balance. Even though semaglutide can’t move freely through the brain, it seems to use these “entry points” like the DVC to activate deeper networks that affect hunger and metabolism.

Other brain areas connected to this region are also involved in feelings of fullness and hormone control. The researchers found that when the Adcyap1-positive neurons were removed, these downstream targets were much less active—even when semaglutide was still in the system.

Yet, structures linked to nausea were still triggered, showing that the positive and negative effects of semaglutide follow different brain circuits. That opens the door to developing new drugs that could mimic semaglutide's benefits while bypassing the pathways that cause people to feel sick.

The team’s findings were published in the journal Cell Metabolism. It’s one of the first studies to clearly map the brain activity behind semaglutide’s effects and separate the benefits from the side effects at the neuron level.

“We are starting to understand how semaglutide works in the brain,” said Linda Engström Ruud, a researcher at the University of Gothenburg and supervisor for the project. “The better we understand this, the greater the opportunity we have to improve them.”

The significance of this research goes beyond weight loss alone. Because GLP-1 receptor agonists like semaglutide are now being tested for other uses—including treatment for addiction and neurodegenerative diseases—it’s critical to know how these drugs behave in the brain.

As millions of people begin using these drugs for obesity and related conditions, understanding the basic biology behind them becomes even more essential. With this new information, scientists may soon be able to fine-tune treatments so they work faster, last longer, and produce fewer side effects.

Instead of asking patients to tolerate nausea or risk muscle loss, doctors may one day offer targeted options that speak only to the brain’s hunger-control circuits. And the discovery of these Adcyap1-positive neurons could be the key to making that future possible.

Note: The article above provided above by The Brighter Side of News.

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