Stanford AI Identifies Natural Weight Loss Molecule 'BRP

Stanford Medicine researchers have identified a naturally occurring molecule that may suppress appetite and reduce body weight with the efficacy of semaglutide—the active ingredient in Ozempic—but without several of its common side effects. The molecule, known as BRP, appears to avoid issues such as nausea, constipation, and significant muscle loss by acting on a more targeted region of the brain.

A Targeted Approach to Metabolism

While semaglutide targets receptors found throughout the body, including the gut and pancreas, BRP appears to act specifically in the hypothalamus. This deep region of the brain is responsible for regulating hunger, body temperature, and energy use. By focusing its activity on this area, the molecule may influence appetite and metabolism without triggering the widespread effects often associated with current weight-loss medications.
In animal studies, the results were significant. Lean mice and minipigs treated with an intramuscular injection of BRP reduced their food intake by as much as 50% within an hour. Furthermore, obese mice treated with daily injections for 14 days lost an average of 3 grams, with the reduction consisting almost entirely of body fat. The treated animals also demonstrated improved glucose and insulin tolerance.

The Role of Artificial Intelligence

The discovery of BRP was made possible by an artificial intelligence algorithm called Peptide Predictor. Researchers used the tool to scan 20,000 human protein-coding genes to identify sites where enzymes known as prohormone convertases typically cut proteins. By narrowing the search to proteins secreted outside the cell, the team reduced a field of thousands of potential candidates to 373 prohormones.
From these, the algorithm estimated that 2,683 distinct peptides could be produced. The research team focused on 100 peptides that showed the highest likelihood of affecting the brain. Among these, BRP—a tiny peptide consisting of only 12 amino acids—produced a tenfold increase in neuronal activity in laboratory tests, outperforming other candidates.

Future Clinical Potential

Despite the promising results in animal models, researchers note that several challenges remain before the molecule can be tested in humans. Because small peptides are often broken down quickly by the body, the team is investigating methods to extend the duration of BRP’s effects to ensure a practical dosing schedule. Additionally, scientists are working to map the specific cell-surface receptors that BRP binds to in order to fully understand its biological pathway.
Senior author Katrin Svensson, PhD, an assistant professor of pathology at Stanford, has co-founded a company to advance the research. The team is eager to determine if the molecule remains safe and effective in human clinical trials, which are planned for the near future. The study, which was published March 5 in Nature, was led by senior research scientist Laetitia Coassolo, PhD.