Research pinpoints the exact neurons responsible for the weight loss effects of GLP-1 drugs
In high amounts, GLP-1 drugs also reduce appetite and signal a feeling of fullness before eating by targeting the brain, but the exact mechanism was not known until now. Photo: iStock
Scientists have figured out how popular medications like Ozempic and Wegovy are helping people shed the kilos. A new study pinpoints a specific group of neurons in the brain as the target for these drugs, offering a clearer picture of their weight-loss mechanism.
These drugs, which contain the active ingredient semaglutide, have been praised for their effectiveness in promoting weight loss. However, the exact way they worked remained a bit of a mystery.
The new research, published in journal Science, revealed that semaglutide interacts with neurons in the dorsomedial hypothalamus, a region of the brain that plays a critical role in regulating appetite, energy expenditure and even our sleep-wake cycle or the circadian rhythm.
Drugs like Ozempic and Wegovy belong to a class of medications known as glucagon-like peptide-1 (GLP-1) receptor agonists. They mimic the GLP-1 hormone that is released in the gastrointestinal tract in response to eating.
Ozempic was first approved to treat type-2 diabetes by the United States Food and Drug Administration (FDA) in 2017. It helps lower sugar levels by promoting the body to produce more insulin.
In high amounts, GLP-1 drugs also reduce appetite and signal a feeling of fullness before eating by targeting the brain, but the exact mechanism was not known until now.
In 2021, the FDA approved Wegovy injection for chronic weight management in adults with obesity or overweight suffering from at least one weight-related condition such as high blood pressure, type 2 diabetes, or high cholesterol. Ozempic has not been authorised for weight loss in the US.
“Patients or people around us who were administered GLP-1 drugs showed satiation for food. But the precise mechanism wasn’t known before and the targets of GLP-1 drugs were not much known,” Kyu Sik Kim from Seoul National University and one of the authors of the study, told Down To Earth.
He explained that past studies have shown satiation centres such as the brainstem and hypothalamus could be involved, but the precise neuronal identity was not identified.
So researchers from South Korea, the United States and the United Kingdom carried out a clinical trial on obese individuals by performing satiation surveys at baseline (before exposure to food cues), pre-ingestive (after exposure to food cues and before eating) and ingestive phases (after eating), with or without GLP-1 treatment.
The team concluded that participants on GLP-1 experienced feeling overall fullness consistently at all three stages compared to those who were not on the drug. The latter group’s overall feeling of fullness declined from baseline to the pre-ingestive phase.
They next analysed brain samples of humans and mice to pin down the neural circuits in the dorsomedial hypothalamus that interact with these medications.
Conducting optogenetic manipulation — a technique that manipulates neuronal activity during behaviour — helped them gain more insights.
When they inhibited the dorsomedial hypothalamus in mice, they noted a significant increase in the total duration of eating and the amount of food consumed. This indicates that neurons in this part of the brain play a role in satiation, noted the study.
When neurons in the dorsomedial hypothalamus were activated as mice were feeding on a high-fat diet, they stopped eating, indicating satiation.
“Our study, for the first time, shows significantly that the GLP-1 receptor neurons in the dorsomedial hypothalamus regulate satiation even before the food is delivered into the gut, a phenomenon that is called pre-ingestive satiation,” Kim explained.
He said future studies should determine the side effects of targeting this region, such as nausea and vomiting. Scientists have recorded that people just starting these drugs commonly face gastrointestinal issues.
The study also calls for more studies to fully address the role of these drugs in cognition. Cognition, Kim noted, is a very large field of study. “Planning to eat, deciding which kind of food to eat and self-reporting how much we are full take precise experimental procedures,” he said.
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