Researchers at Stanford Medicine have identified a naturally occurring molecule that mimics the weight-loss effects of semaglutide—the active ingredient in Ozempic—while potentially avoiding the harsh side effects associated with the blockbuster drug. Testing in animal models shows the peptide, dubbed BRP, drives fat loss and improves metabolic markers by targeting specific brain neurons.
Unlike semaglutide, which acts on receptors throughout the gut and pancreas, BRP appears to operate exclusively within the hypothalamus. This precision is the key to its cleaner safety profile.
"The receptors targeted by semaglutide are found in the brain but also in the gut, pancreas and other tissues," said Katrin Svensson, PhD, assistant professor of pathology at Stanford Medicine. "That's why Ozempic has widespread effects including slowing the movement of food through the digestive tract and lowering blood sugar levels. In contrast, BRP appears to act specifically in the hypothalamus, which controls appetite and metabolism."
Using AI to find hidden hormones
The discovery process utilized a custom-built artificial intelligence tool called Peptide Predictor to scan over 20,000 human protein-coding genes. The team sought specific prohormones—inactive molecules that the body cuts into smaller, functional peptides—that could be linked to metabolic regulation.
Researchers narrowed their search to 373 candidates before identifying 2,683 possible peptides. Laboratory testing of these candidates eventually revealed that BRP, a peptide consisting of only 12 amino acids, produced a tenfold increase in neuronal activity compared to control cells.
In preclinical trials, the results were pronounced. A single injection of BRP in minipigs reduced food intake by 50% within an hour. In obese mice, a two-week regimen resulted in significant fat loss while preserving muscle mass, a common point of failure for existing GLP-1 agonists.
Notably, the treated animals showed no signs of the nausea, anxiety, or digestive disruption that often plague patients using current weight-loss injections. The study, published in the journal Nature, confirms that BRP functions through biological pathways entirely distinct from those used by semaglutide.
Svensson, who served as the senior author of the study, has co-founded a company to advance the molecule toward human clinical trials. Lead author and senior research scientist Laetitia Coassolo, PhD, is currently working with the team to map the specific receptors that interact with BRP to finalize the therapeutic approach.
