People who Wegovy and similar weight loss medications often feel full, even if they sit down to eat and haven't taken a single bite. Now scientists have discovered a region of the brain that is involved in this effect - and that helps produce the same sensation without the use of weight loss medications to evoke.

In one today inScience 1In a published paper, scientists describe two groups of neurons related to satiety: one for pre-satiation and one for post-satiation. The study also shows that the blockbuster weight loss medications act on the 'saturation' neurons, but further research is needed to determine the mechanisms of action of the treatments, the authors say.

Identifying these two populations of neurons is the main contribution of the work, says Allison Shapiro, a neurodevelopmental specialist at the University of Colorado Anschutz Medical Campus in Aurora, who was not involved in the research. It fits the anecdotal idea that there are two types of satiety: one that is anticipatory and another that occurs in response to eating. "Based on what they found, it appears that this specific area of ​​the hypothalamus is responsible for both, which is pretty cool."

satiety without food

The latest obesity drugs mimic a hormone called glucagon-like peptide 1 (GLP-1), which controls blood sugar levels and acts on the brain to suppress appetite. GLP-1 drugs include semaglutide, sold as Ozempic for type 2 diabetes (T2D) and Wegovy for weight loss, and liraglutide, sold as Saxenda for weight loss and 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 anti-obesity drug. “I felt a huge increase in satiety when I saw and smelled food even before I started eating,” he says. This motivated him to delve deeper into the feeling of pre-saturation.

He and his colleagues recruited people with obesity and asked them to report their level of satiety at three stages: before exposure to food; at the sight of a delicious plate of Korean fried chicken but before eating; and after eating. People taking liraglutide felt full even before coming into contact with food, but this feeling increased when they were shown food and again after they ate. The results show that Choi isn't the only one who gets full at the mere sight of food, unlike the participants who didn't take the drug. a feeling the team called 'prandial satiety'.

In contrast, for participants who didn't take the drug, satiety decreased when they saw the fried chicken and only increased again after they ate.

To identify the area of ​​the brain responsible for these sensations, researchers focused on the dorsomedial hypothalamus (DMH). Its neurons have GLP-1 receptors, which allow GLP-1 to act directly on this area of ​​the brain.

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

Neurons that signal 'I'm full'

Having established this, the authors examined the activity of individual neurons in the mouse DMH. They identified two populations of neurons: one that was continuously active from the moment the mice began foraging until the time they began eating, and another that was active only when the mice were eating.

The authors also showed that GLP-1 drugs act on the DMH. In mice that received liraglutide, neuronal activity in this brain region was higher before and during meals than in mice that did not receive the drug. The team deleted GLP-1 receptors in the DMH neurons of some animals, which inhibited liraglutide's ability 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 was weakened.

Karolina Skibicka, a neuroscientist at Penn State in University Park and the University of Gothenburg, Sweden, notes that other studies have not observed such changes in feeding behavior after manipulating GLP-1 receptors in this brain area 2. A possible explanation could be related to the two populations of neurons discovered in the DMH. “We tend to think of GLP-1 receptor-expressing neurons in a given brain area as a homogeneous population that all play the same role,” she says. "This work shows that this is obviously not the case. It's just one area of ​​the brain, but GLP-1 receptors on neurons do different things there."

The study showed congruence between what was observed in humans and mice, says Amber Alhadeff, a neuroscientist at the Monell Chemical Senses Center in Philadelphia, Pennsylvania. She notes that it is becoming increasingly important to incorporate clinical observations into basic research on GLP-1 drugs. "But then it's also important to go back and then confirm the existence of these mechanisms in humans. This work was a nice example of it going both ways."