12-amino acid BRP peptide (the sphere is atomic and the stick is a combination) inhibits appetite and reduces the weight gain of mice and pigs without causing nausea or disgust. Credit: Katrin SVENSSON/Stanford Medicine
Natural molecules that are identified by Stanford Medical Researchers look similar to Semaglutide (Ozempic) by inhibiting appetite and weight loss. In particular, tests in animals have also shown that they are effective without side effects such as significant losses of nausea, constipation and muscle mass.
The newly discovered molecule, BRP, acts through a separate similar metabolic path and activates other neurons in the brain to provide a more targeted approach to weight loss.
Pathology Professor Katrin Svensson, Ph.D.
“This is why Ozempic has a wide range of effects, such as slowing down the movement of food through the digestive tract and lowering blood sugar levels. In contrast, BRP seems to work specifically in the hypothalamus that controls appetite and metabolism.”
Svensson co -established a company and started a human molecular clinical trial in the near future.
SVENSSON is the chief author of the researchIt has been published nature. Senior Research Scientist Dr. Laetitia Coassolo is the chief author of this study.
This study would have been impossible without using artificial intelligence.
Prohormones are biologically inert molecules activated when cut into small pieces called peptides by other proteins; Some of these peptides function as hormones that control complex biological results, including energy metabolism in brain and other organs.
Each Tormon can be divided into various ways. However, as a traditional protein separation method, it is difficult to pick peptide hormones (relatively rare) from the biological soup of much more natural by -products of protein decomposition and processing.
The researchers focused on the Prohormone Converase 1/3 (also called PCSK1/3), known to separate prohormones from certain amino acid sequences and to be involved in human obesity.
One of the peptide products is glucagon-like peptide 1 or GLP-1 that controls appetite and blood sugar levels; Semaglutide works with the effect of GLP-1 in the body. The team switches to artificial intelligence to help you identify other peptides related to energy metabolism.
Peptide
Instead of identifying hundreds of thousands of peptides by manually separating proteins and peptides from tissues and using technologies such as mass analysis, researchers designed a computer algorithm called “peptide prediction factor” to check the typical Prohormone converter razet cutting site in 20,000 human protein-coding genes.
Then we focused on the gene (core characteristics of hormones) encoding proteins secreted outside of cells and focused on genes with four or more possible cutting sites. That way, the search has narrowed to 373 prohormones, which are managed numbers that can select biological effects.
“The algorithm was absolutely the key to our findings.
The peptide predictor predicted that the pro -hormone converter 1/3 would produce 2,683 unique peptides from 373 proteins. CoASSOLO and SVENSSON focused on sequences that are likely to be biologically activated in the brain. They screened 100 peptides, including GLP-1, for the ability to activate neuron cells that grew up in the laboratory.
As expected, the GLP-1 peptide has a strong effect on neuron cells and triples their activity for control cells. However, a small peptide consisting of just 12 amino acids increased the activity of cells by 10 times more than the control. The researchers have nominated this peptide BRP based on their parents’ Prohormone, BPM/RETINO ACID -guided neuroscopic 2 or Brinp2 (Brinp2 -related peptide).
When the researchers tested the effects of BRP on the Lin Mouse and the mini -pigs (reflect human metabolism and meal patterns more closely than the mouse), the muscles of the BRP were found to reduce the food intake by up to 50%in the next time in the two animal models.
Obesity mice treated as BRP’s daily injections for 14 days lost an average of 3 grams (almost entirely due to fat loss, the control animal also got about 3 grams for the same period, and the mouse also showed improved glucose and insulin resistance.
Action studies on mice and pigs have found that there is no difference in actions such as movements, water intake, anxiety of the treated animals. Further studies on physiological and brain activity showed that BRP activated the metabolism and neuron paths separated from the GLP-1 or Semaglutide.
Researchers hope to identify cell surface receptors that combine with BRP and add the path of action. In addition, if the peptide is effective in regulating the human body weight, we are investigating how the effect of the peptide lasts longer in order to allow more convenient administration schedules.
Svensson said, “The lack of effective drugs to treat human obesity has been a problem for decades. “We have tested that we have never compared with the appetite and weight loss of Semagluide. We want to learn whether it is safe and effective for humans.”
Researcher at the University of California at Berkeley; Minnesota University; British Columbia University has contributed to this work.
Svensson and CoASSOLO are inventors of patents on BRP peptides for metabolic disorders. Svensson is a co -founder of Merrifield Therapeutics.
Additional information:
Laetitia Coosolo et al, prohormone cutting prediction reveals non -human anti -besity peptides. nature (2025). Doi: 10.1038/S41586-025-08683-Y
recall: Ozempic, Sidesteps side effect of naturally occurring molecular rival weight loss (March 6, 2025) March 9, 2025
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