Stanford Medicine researchers have identified a naturally occurring 12-amino-acid peptide named BRP that suppresses appetite and reduces body weight in animal studies while appearing to avoid common side effects of weight-loss drugs like semaglutide, according to a study published March 5 in Nature.
The discovery could offer a more targeted method for treating obesity. While widely used medications such as Ozempic target receptors distributed across the gut, pancreas, and brain, BRP appears to act specifically within the hypothalamus, the brain region governing hunger and energy expenditure.
Artificial Intelligence Discovers Hidden Prohormone Fragments
The identification of BRP relied heavily on artificial intelligence to sift through thousands of potential protein fragments. Lead author Laetitia Coassolo and senior author Katrin Svensson utilized a custom computer algorithm called Peptide Predictor to analyze the human genome.
Proteins known as prohormones act as inactive precursors that enzymes cut into smaller functional peptides. Traditional laboratory isolation methods generate overwhelming volumes of data, requiring researchers to sort through hundreds of thousands of molecules.
The research team focused on prohormone convertase 1/3, an enzyme connected to human obesity that cuts prohormones at specific amino acid sequences. Running Peptide Predictor across 20,000 human protein-coding genes identified 373 secreted prohormones containing at least four potential cleavage sites.
The algorithm estimated that prohormone convertase 1/3 could generate 2,683 distinct peptides from those proteins. Testing 100 high-priority sequences on laboratory-grown neuronal cells revealed that a tiny 12-amino-acid peptide, designated BRP from its parent prohormone BRINP2, increased neuronal activity tenfold compared to untreated controls.
Animal Studies Show Significant Weight Reduction
Following cell tests, the researchers evaluated BRP in lean mice and minipigs. According to the findings, an intramuscular injection administered prior to feeding reduced food intake over the next hour by up to 50% in both species.
In a 14-day trial providing daily injections to obese mice, treated animals lost an average of 3 grams, with the reduction coming almost entirely from body fat. Control mice gained approximately 3 grams over the same timeframe. Treated animals also demonstrated improved glucose and insulin tolerance.
Behavioral testing indicated no meaningful differences in water consumption, movement, anxiety-like behavior, or fecal production between treated and untreated animals. The absence of changes in fecal production is notable because treatments containing semaglutide frequently slow digestion and cause constipation. The study also reported no observations of nausea-related responses or major muscle loss.
Future Outlook and Human Clinical Trials
Svensson, an assistant professor of pathology at Stanford, has co-founded a company named Merrifield Therapeutics to advance the molecule. The startup plans to initiate human clinical trials of BRP in the near future.
Before human testing proceeds, researchers aim to identify the specific cell-surface receptors that bind to BRP and map the downstream signaling events. Another objective is extending the peptide’s duration of action, as small peptides typically break down quickly inside the body.