People taking Wegovy and similar weight-loss drugs often feel full, even when they sit down to a meal and haven’t taken a single bite. Now, scientists have found a brain region that is involved in this effect — and that helps to cause the same sensation without the use of weight-loss drugs.

In a paper published today in Science¹, scientists describe two groups of neurons associated with feeling full: one for pre-meal fullness, and one for post-meal fullness. The study also shows that the blockbuster obesity drugs act on the ‘fullness’ neurons, but more research is needed to determine the treatments’ mechanism, the authors say.

The identification of these two populations of neurons is the paper’s key contribution, says Allison Shapiro, a specialist in neurodevelopment at the University of Colorado Anschutz Medical Campus in Aurora, who was not involved in the research. It fits in with the anecdotal idea that there are two types of fullness: one that is anticipatory, and another that arises in response to eating. “Based on what they’ve found, it appears that this specific region of the hypothalamus is responsible for both, which is pretty cool.”

Fullness without food

The latest obesity medications mimic a hormone called glucagon-like peptide 1 (GLP-1), which controls blood-sugar levels and acts on the brain to curb appetite. The GLP-1 drugs include semaglutide, sold as Ozempic for type 2 diabetes (T2D) and as Wegovy for weight loss, and liraglutide, sold as Saxenda for weight loss and as Victoza for T2D. Both are manufactured by Novo Nordisk, based in Bagsværd, Denmark.

Study co-author Hyung Jin Choi, a neuroscientist at Seoul National University, experienced the effects of liraglutide firsthand when he took the drug for obesity. “I felt a huge increase in fullness when I saw and smelled food, even before I started eating,” he says. This motivated him to dig into the feeling of pre-meal fullness.

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He and his colleagues recruited people with obesity and asked them to report their level of satiation at three stages: before exposure to food; while looking at a delicious plate of Korean fried chicken but before eating it; and after eating it. People taking liraglutide felt full even before exposure to food, but this feeling grew when they were shown food and again after they’d eaten. The findings demonstrate that Choi isn’t the only one taking the drug who feels full at the mere sight of food — a feeling that the team named ‘preingestion satiation’.

By contrast, for participants who weren’t taking the drug, satiation decreased at the sight of the fried chicken and didn’t rise again until after they’d eaten.

To identify the area of the brain that is responsible for these sensations, researchers homed in on the dorsomedial hypothalamus (DMH). Its neurons have GLP-1 receptors, allowing GLP-1 to act directly on this brain region.

The researchers artificially stimulated DMH neurons in mice that were in the middle of a meal and found that the animals stopped eating immediately. When these neurons were chronically activated, mice ate less; when they were chronically inhibited, mice ate more. The results suggest that the region plays a central part in satiation.

Neurons that signal ‘I’m stuffed’

With that established, the authors investigated the activity of individual neurons in the mouse DMH. They identified two populations of neurons: one that was consistently active from the moment that mice started seeking food to the moment that they started eating, and another that was consistently active only as the mice ate.

The authors also showed that GLP-1 drugs act on the DMH. In mice that received liraglutide, neural activity in this brain region was higher before and during meals than in mice that hadn’t received the drug. The team deleted GLP-1 receptors in some animals’ DMH neurons, curbing the ability of liraglutide to act on this brain area. The mice ate more than those with functioning GLP-1 receptors, suggesting that liraglutide’s ability to suppress appetite had been weakened.

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Karolina Skibicka, a neuroscientist at Penn State in University Park and the University of Gothenburg, Sweden, notes that other studies have found no such changes in feeding behaviour after manipulation of GLP-1 receptors in this brain area². One possible explanation might be related to the two neuronal populations in the DMH discovered by the authors. “We tend to think of GLP-1-receptor-expressing neurons in a given brain area as this homogeneous population playing the same role,” she says. “This paper is showing that that’s clearly not true. It’s just one brain area, but GLP-1 receptors on neurons are doing different things there.”

The study showed a congruence between what was seen in humans and in mice, says Amber Alhadeff, a neuroscientist at the Monell Chemical Senses Center in Philadelphia, Pennsylvania. She notes that it’s becoming increasingly important to use clinical observations to inform the basic research on GLP-1 drugs. “But then, it’s also important to go back and subsequently confirm the existence of these mechanisms in humans. This paper was a nice example of taking that in both directions.”