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Seoul – GLP-1 agonists such as liraglutide or semaglutide have a direct effect on nerve cells in the dorsomedial hypothalamus. They stimulate neurons there that trigger a feeling of satiety before food intake, which Korean researchers in Science (2024; DOI: 10.1126/science.adj2537) as “preingestive satiation.” The researchers have examined the connections more closely in mice.

The effectiveness of GLP-1 agonists in weight loss is beyond doubt. However, the mechanism of action is still unclear. It was known that the drugs imitate the effect of the body’s own hormones, which are released by the stomach and intestines during meals, and that the effect is mediated via the appetite centers in the brain. Receptors to which GLP-1 agonists bind have been discovered on nerve cells in the dorsomedial hypothalamus.

Many patients report that GLP-1 agonists generally reduce the desire to eat. A team led by Hyung Jin Choi from Seoul National University investigated this in human subjects. The participants filled out questionnaires before eating, when they saw the food and when they consumed it. In a control group, the feeling of fullness only set in when they ate. Treatment with the GLP-1 agonist, on the other hand, meant that just the sight of the food made them feel full.

The researchers then investigated the connections in mice. They implanted probes into the animals that can activate specific nerve cells using a beam of light (for this optogenetic experiment, the nerve cells had previously been equipped with a light-sensitive receptor in the retina). When the researchers turned on the lamp implanted in the brain, the mice immediately stopped eating; when the lamp was turned off, they continued eating.

Using a microendoscope, the researchers were able to distinguish between two different groups of nerve cells. One group became active as soon as the mice smelled the food and began searching for it. According to Choi, these cells could be responsible for “preingestive satiation.”

In one experiment, mice lost interest in foraging after they had been injected with a GLP-1 agonist. This was probably due to increased activation of the preingestive satiation neurons. The second group of nerve cells was only activated when the animals began to eat.

The study confirms the reports of patients who report premature satiety after treatment with GLP-1 agonists. The natural function of the “preingestive satiety” neurons could be to protect animals from eating too much. In obese people, this protective mechanism no longer seems to work. © rme/aerzteblatt.de