Weight-Loss Drugs Target the Brain to Cause Satiation Before Eating: Study

Although the effects of GLP-1 receptor agonists are understood, a new study sheds more light on how exactly they work.

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Glucagon-like peptide-1 (GLP-1) receptor agonists, the active ingredient in weight-loss drugs such as tirzepatide and semaglutide, promote satiation even before a person begins his or her meal, a new study suggests.

The findings, published in Science last month, indicate that the drug influences a brain pathway in the hypothalamus, causing a person to feel full when he or she encounters food.

“Humans injected with GLP-1 receptor agonists experienced a higher degree of satiation merely from seeing or smelling food, even before ingesting it,” one of the authors, Dr. Joon Seok Park, said in a video about the study.

GLP-1 receptor agonists have been on the market since 2017 when the U.S. Food and Drug Administration (FDA) approved semaglutide Ozempic as a treatment for Type 2 diabetes. In 2021, the FDA approved Wegovy, another semaglutide, for chronic weight management in adults suffering from at least one weight-related health condition, such as high blood pressure, Type 2 diabetes, or high cholesterol.

While GLP-1 receptor agonists are known to cause satiation, or feelings of fullness, many researchers have not yet agreed on exactly how they work.

“As scientists, we believe that understanding the brain’s regulation of eating behavior is crucial for gaining a better understanding of obesity and developing more effective therapeutic solutions,” Hyung Jin Choi, a professor of endocrinology and author of the study, said in the video.

Targeting the Hypothalamus

The drugs target neurons in the dorsomedial hypothalamus, a cluster of neurons in the hypothalamus. This area of the brain regulates feeding, drinking, body weight, and circadian activities.

The authors found that GLP-1 receptors target neurons in this area. These neurons can induce immediate feelings of satiation and pre-ingestive satiation, which occurs before a person or animal actually begins eating.

Pre-ingestive satiation signals to the body that it is about to receive food that must be digested and that calories must be processed. However, the researchers theorized that if that process is interrupted, it will lead to an increased feeling of fullness and, therefore, weight loss.

After studying the brains of humans and mice before and after they ate, the researchers discovered they were right.

The mice and humans injected with GLP-1 receptor agonists felt more satiated before eating. Additionally, mice that received neuronal stimulation in the middle of a meal stopped eating immediately. The more often these neurons were activated, the less the mice ate.

The researchers believe their findings will help in the development of new anti-obesity drugs that can better target the dorsomedial hypothalamus to improve outcomes for people struggling with being overweight or obese.

Complex Reactions

Apart from controlling fullness, GLP-1 receptor agonists are involved in many complex reactions, and their mechanism is still unclear.

Beyond metabolism, studies have suggested that GLP-1 receptor agonists may have neuroprotective effects in preventing Parkinson’s and Alzheimer’s disease.

When administered, GLP-1 receptor agonists activate the sympathetic nervous system, which is involved in the fight-or-flight response. This could potentially affect how the body burns fat. It also lowers blood sugar levels by encouraging insulin release.

Furthermore, GLP-1 receptor agonists inhibit the stomach from emptying its contents into the intestines, which may further promote a sense of fullness. Some studies suggest that this may also be linked to the drug’s side effects of nausea and vomiting.

Side effects of GLP-1 receptor agonists include dizziness, mild increase in heart rate, infections, headaches, and upset stomach.