Korean Researchers Unveil the Secret Behind 'GLP-1' Weight Loss Drugs
Choi Hyung-Jin and his team at Seoul National University School of Medicine identify world's first 'artificial reason for fullness'
Professor Choi Hyung-jin’s team from Seoul National University Medical School has made a groundbreaking discovery about the mechanism behind the powerful weight loss effects of GLP-1-based obesity treatments, such as Saxenda and Wegovy.
GLP-1 (Glucagon-Like Peptide-1) is a hormone released from the intestines, known to play a role in regulating blood sugar levels, maintaining a sense of fullness, and suppressing appetite. However, Korean researchers have become the first in the world to uncover that these GLP-1 obesity drugs activate neural pathways in the brain's hypothalamus, causing a feeling of fullness merely by seeing food.
The study, led by Professor Hyung-jin Choi from the Department of Anatomy at Seoul National University College of Medicine, focused on the cognitive mechanisms of fullness induced by GLP-1 through hypothalamic circuits. Titled "GLP-1 increases preingestive satiation via hypothalamic circuits in mice and humans," the research was published in the online edition of the prestigious journal Science on the 28th. Key contributors included graduate student Kim Kyu-sik and medical graduate Park Jun-seok.
The researchers initially observed that patients administered GLP-1 obesity drugs reported feeling full just by thinking about or seeing food. To investigate, they used MRI (Magnetic Resonance Imaging) to analyze the distribution of GLP-1 receptors in the brain tissues of these patients.
The results revealed a high concentration of GLP-1 receptors in the dorsomedial hypothalamus (DMH) of the brain. Similar findings were noted in experiments with mice.
Using optogenetics, a technique that visualizes brain signal transmission, the team artificially activated GLP-1 receptors in the DMH of mice. This induced a sense of fullness, causing the mice to stop eating. Conversely, inhibiting these receptors eliminated the sense of fullness, prompting the mice to continue eating.
Additionally, through calcium imaging, which allows the visualization of brain signal transmission, the team trained mice to associate specific places or actions with food. For instance, pressing a lever would dispense food or placing food in a specific location.
When these trained mice were presented with such scenarios, the GLP-1 receptor neurons in their DMH were activated. Consequently, the mice, feeling full, did not attempt to obtain food. The same brain neurons became more sensitive when the mice were given GLP-1 drugs.
Professor Choi suggested that leveraging this mechanism could lead to the development of new obesity treatments that minimize side effects while maximizing efficacy. He noted, “Current GLP-1 drugs like Saxenda and Wegovy have reported side effects such as nausea, vomiting, and lethargy. By precisely targeting the activation of hypothalamic neurons, we could induce only the sensation of fullness, thereby reducing these side effects.”
Furthermore, Professor Choi highlighted the high cost of these GLP-1 drugs due to the synthesis of amino acid sequences. “If we apply this technology to synthesize low molecular weight compounds like aspirin, we could potentially develop more affordable oral pills,” he added.
This breakthrough could pave the way for more effective and accessible treatments for obesity, benefiting countless individuals worldwide.