Researchers at Stanford Medicine have identified a naturally occurring molecule in the human body that can suppress appetite and reduce body weight in a way similar to semaglutide, widely known as Ozempic. Animal testing showed that the new molecule worked without some of the typical side effects associated with the drug, such as nausea, constipation, and more pronounced muscle loss. The topic was brought to attention by sciencedaily.com.

The newly identified molecule is called BRP, and it works through a distinct but related metabolic pathway. It activates different neurons in the brain than Ozempic does, which could offer a more targeted way to regulate appetite and body weight.

BRP appears to act more precisely in the part of the brain that controls hunger and metabolism

The key difference between BRP and semaglutide lies in where they act. Katrin Svensson, assistant professor of pathology at Stanford Medicine and the study’s senior author, explained the mechanism:

“The receptors targeted by semaglutide are found in the brain but also in the gut, pancreas and other tissues,” Svensson said. “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.”

Svensson has also co-founded a company that aims to begin clinical testing of the molecule in humans in the near future. The study was published on March 5 in the journal Nature.

Artificial intelligence helped identify thousands of possible candidates

According to the researchers, the discovery would not have been possible without artificial intelligence, which helped sift through a large number of proteins from a group known as prohormones. These are biologically inactive molecules that can be cleaved into smaller pieces called peptides, some of which can then function as hormones that regulate complex processes in the body.

The researchers focused on the enzyme prohormone convertase 1/3, which cleaves prohormones at specific sites and is known to play a role in obesity. One product of this process is GLP-1, a hormone that regulates appetite and blood sugar levels. Semaglutide works by mimicking its effects.

Instead of relying on traditional protein-isolation methods, the team created a computer algorithm called Peptide Predictor. It identified typical cleavage sites across all roughly 20,000 human protein-coding genes.

After narrowing the search to proteins that are secreted outside the cell and contain four or more possible cleavage sites, the team was left with 373 prohormones. From these, the algorithm predicted 2,683 unique peptides.

Just 12 amino acids, yet a much stronger effect on neuronal activity

The researchers then tested 100 peptides, including GLP-1, on lab-grown neurons. While GLP-1 increased cell activity about threefold compared to controls, one small peptide made up of only 12 amino acids increased activity by as much as tenfold.

The researchers named this peptide BRP after its parent molecule, BRINP2 (short for BRINP2-related peptide).

A single dose reduced food intake by up to half

In tests on lean mice and minipigs, which in some respects reflect human metabolism more closely than mice do, a single injection of BRP before feeding reduced food intake by up to 50% over the following hour.

In obese mice, daily BRP injections over 14 days led to an average weight loss of 3 grams, almost entirely from fat tissue. Control animals, by contrast, gained about 3 grams over the same period. The treated animals also showed improved glucose and insulin tolerance.

Importantly, behavioral testing found no differences in movement, water intake, anxiety-like behavior, or stool production in the treated animals.

Researchers now want to determine whether BRP will be safe and effective in humans

The researchers are now working to identify the receptors BRP binds to and to better understand its mechanism of action. They are also investigating how to extend the peptide’s effects in the body so that, if successful, it could be administered on a more convenient schedule.

“The lack of effective drugs to treat obesity in humans has been a problem for decades,” Svensson added. “Nothing we’ve tested before has compared to semaglutide’s ability to decrease appetite and body weight. We are very eager to learn if BRP is safe and effective in humans.”

The study was funded by the National Institutes of Health, Stanford’s SPARK Translational Research Program, Stanford Bio-X, and several other organizations. Svensson and Coassolo are also listed as inventors on patents related to BRP peptides for metabolic disorders.