Introduction
For the first time, a joint research team from South Korea and the United States has uncovered the specific mechanism by which popular obesity drugs reduce weight. While it was previously known that these drugs work by suppressing appetite and promoting a feeling of fullness, this study is the first to identify the precise neural pathways involved. This advancement is expected to enhance the efficacy of obesity drugs and potentially extend their use to other medical conditions.
Key Findings from the Study
Discovery of Neural Pathways
Professor Choi Hyung-jin of Seoul National University (SNU) College of Medicine and Professor Kevin Williams of the University of Texas UT Southwestern Medical Center announced on June 27 that glucagon-like peptide (GLP-1) analogs, used in obesity treatment, increase satiety through neurons in the middle and dorsum of the hypothalamus. Their findings were published in the June 28 issue of the journal Science.
Role of GLP-1
GLP-1, a hormone released by the stomach and small intestine during meals, plays a crucial role in post-meal satiety. Initially introduced in 2005 as diabetes medications, GLP-1 mimicking drugs shifted focus to obesity treatment following observations of significant weight loss as a side effect in patients. This transition mirrors the development of Viagra, originally intended for heart disease but repurposed for erectile dysfunction due to unexpected side effects.
Obesity Drugs in Focus
Wegovy and Ozempic
The Danish pharmaceutical company Novo Nordisk developed Ozempic for diabetes and Wegovy for obesity, both utilizing the GLP-1 analog semaglutide. Wegovy for obesity and Ozempic for diabetes, developed by the Danish pharmaceutical company Novo Nordisk, both utilize the GLP-1 analog semaglutide.
Mounjaro and Zepbound
The U.S. company Eli Lilly introduced Mounjaro for diabetes and Zepbound for obesity, employing the compound tirzepatide. With once-weekly doses, Wegovy has reduced weight by up to 15% and Zepbound by up to 25.3%. The soaring demand for these medications has led to shortages.
Research Methodology
Genetically Engineered Lab Mice
The research team employed genetically engineered lab mice with neural circuits responsive to light stimulation. They identified the nerves binding to GLP-1 by directly stimulating specific hypothalamic regions. The activation of the DMH nerve, abundant in GLP-1 receptors, resulted in the mice ceasing to eat, indicating satiety. Conversely, inhibiting this neural circuit prolonged the eating duration in mice.
Leading Researcher: Professor Choi Hyung-jin
Professor Choi, who led the study, is a leading Korean physician-scientist. An alumnus of SNU College of Medicine, he earned his master’s degree in internal medicine and a doctorate in molecular medicine. After a clinical career at SNU Hospital and Chungbuk National University Hospital, he transitioned to research in 2015, joining SNU College of Medicine’s Department of Anatomy.