Ozempic and similar drugs have changed the approach to weight loss, but their use is often limited by side effects such as nausea, constipation, and muscle loss. These effects are linked to the extensive way these drugs act throughout the entire body. Researchers have been looking for a more targeted solution.
A team at Stanford Medicine has now identified a naturally occurring molecule that suppresses appetite and promotes fat loss in animal studies, without many of the side effects linked to semaglutide, the main ingredient in Ozempic.
The discovery, published in Nature, was made using artificial intelligence and reveals a molecule that acts through a different biological pathway.
A Different Kind of Signal
The molecule, named BRP, is a peptide, or a small protein fragment, consisting of 12 amino acids. Evidence suggests it acts specifically on the hypothalamus, the part of the brain that regulates appetite and metabolism.
This targeted action makes BRP different from semaglutide, which mimics the hormone GLP-1. Since GLP-1 receptors exist throughout the body, Ozempic influences many systems simultaneously, including digestion, blood sugar regulation, and appetite.
“The receptors targeted by semaglutide are found in the brain but also in the gut, pancreas and other tissues,” said senior author Katrin Svensson, PhD, an assistant professor of pathology at Stanford. “In contrast, BRP appears to act specifically in the hypothalamus, which controls appetite and metabolism.”
The study’s abstract reports that BRP acts independently of the GLP-1 receptor, leptin, and the melanocortin 4 receptor, three major pathways involved in appetite regulation. This suggests BRP represents a distinct mechanism for controlling appetite.
Identified by AI
The discovery started with computational analysis. The research team developed an algorithm, Peptide Predictor, to scan all 20,000 human protein-coding genes. The team aimed to identify where enzymes could cut large inactive molecules, known as prohormones, into smaller, potentially active peptide fragments.
From this list, the researchers selected 100 peptides for testing in cultured brain cells. GLP-1 produced a significant response, but BRP produced a response ten times stronger.
“The algorithm was absolutely key to our findings,” Svensson said.
Results from Animal Studies
In studies with lean mice and minipigs, which more closely reflect human metabolism than standard mice, a single injection of BRP before feeding reduced food intake by up to 50% within an hour.
For obese mice that received daily injections for 14 days, the average weight loss was 3 grams, primarily from fat. In contrast, untreated mice gained about 3 grams during the same period. Treated animals also showed better glucose and insulin tolerance.
Importantly, the animals did not show changes in movement, water intake, anxiety-like behavior, or digestion. These are the types of side effects that have limited the use of GLP-1 drugs for some patients.
What Comes Next
Researchers are continuing to investigate which receptors BRP interacts with and are working to develop longer-lasting formulations that could be suitable for human use. For researchers seeking a more precise alternative to GLP-1 drugs, BRP represents a promising new direction. Svensson has co-founded Merrifield Therapeutics, a company planning to start human clinical trials in the near future.
“The lack of effective drugs to treat obesity in humans has been a problem for decades,” Svensson said. “Nothing we’ve tested before has compared to semaglutide’s ability to decrease appetite and body weight. We are very eager to learn if it is safe and effective in humans.”
Austin Burgess is a writer and researcher with a background in sales, marketing, and data analytics. He holds an MBA, a Bachelor of Science in Business Administration, and a data analytics certification. His work focuses on breaking scientific developments, with an emphasis on emerging biology, cognitive neuroscience, and archaeological discoveries.