Why is the Weight Loss Miracle Drug Effective?

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Why is the Weight Loss Miracle Drug Effective? Latest Science Paper: Tricking the Brain into Feeling Full Before Eating

Why is the Weight Loss Miracle Drug Effective? Latest Science Paper: Tricking the Brain into Feeling Full Before Eating

The emergence of GLP-1 receptor agonists (GLP-1RA) as weight loss medications has allowed people to achieve weight loss results that were previously only possible through surgery. For instance, semaglutide can lead to approximately 15% weight reduction, while tirzepatide can achieve over 20% weight reduction.

Initially, GLP-1 receptor agonists were used to treat type 2 diabetes by promoting the production of glucagon-like peptide-1 (GLP-1) to regulate blood sugar levels. However, researchers noticed that patients using these medications often experienced significant weight loss, which was attributed to reduced appetite. Nowadays, GLP-1 receptor agonists are increasingly used for weight loss. Despite their popularity, the exact mechanisms behind their effects are not fully understood. Many researchers are working to determine which parts of the brain are influenced by GLP-1 receptor agonists and why these drugs create a sense of fullness, leading to effective weight loss.

On June 27, 2024, researchers from Seoul National University and the University of Texas Southwestern Medical Center published a paper in the prestigious journal Science titled “GLP-1 increases preingestive satiation via hypothalamic circuits in mice and humans.”

The study reveals that GLP-1 receptor agonists can induce a sense of fullness before eating by activating the DMHGLP-1R-ARCNPY/AgRP neural circuits, explaining why these drugs are so effective at promoting weight loss. This discovery also offers new neural targets for treating obesity and metabolic diseases.

Why is the Weight Loss Miracle Drug Effective? Latest Science Paper: Tricking the Brain into Feeling Full Before Eating

GLP-1 receptor agonists (GLP-1RA) are effective weight loss drugs. However, their precise mechanisms of action in the central nervous system remain unclear.

In this study, the research team first conducted trials with obese volunteers to assess their sense of fullness before and after eating a plate of fried chicken. They found that volunteers who used GLP-1 receptor agonists reported feeling full before eating and even more so after eating.

Analysis of brain samples from humans and mice indicated that neurons expressing GLP-1 receptors (GLP-1R) in the dorsomedial hypothalamus (DMH) are candidate neurons for encoding pre-ingestive fullness.

The research team then conducted further studies on mouse models, which showed that optogenetic stimulation of DMHGLP-1R neurons induced a sense of fullness. Calcium imaging indicated that these neurons are actively involved in encoding pre-ingestive fullness. The use of GLP-1 receptor agonists selectively increased the activity of DMHGLP-1R neurons during eating behavior.

Furthermore, the team discovered that after GLP-1 receptor agonists activate DMHGLP-1R neurons, these neurons interact with NPY/AgRP neurons (ARCNPY/AgRP neurons) in the arcuate nucleus (ARC) of the hypothalamus. The complex interactions between these neurons regulate food intake. This means that GLP-1 receptor agonists affect both DMHGLP-1R neurons and ARCNPY/AgRP neurons, explaining why these drugs are so effective for weight loss.

Overall, these findings reveal the hypothalamic mechanisms through which GLP-1 receptor agonists control pre-ingestive fullness, providing new neural targets for treating obesity and metabolic diseases.