AI-Powered Discovery of a Novel"Magic Peptide"for Weight Loss,Expected to Surpass Semaglutide!
Over the past few decades,the problem of obesity has spread rapidly worldwide,posing numerous health risks.Despite this,effective obesity treatment drugs have been scarce until the advent of the GLP-1 receptor agonist semaglutide,which brought a glimmer of hope to obesity treatment.However,although GLP-1 class drugs like semaglutide can effectively reduce appetite and blood sugar levels to aid weight loss,their side effects,such as nausea,vomiting,anorexia,and significant muscle loss,have also caused considerable distress to patients.Therefore,how to reduce these side effects while achieving weight loss goals has become a key direction for the development of the next generation of weight loss drugs.
On March 5,2025,a research team led by Katrin Svensson from Stanford University School of Medicine published a groundbreaking research paper titled"Prohormone cleavage prediction uncovers a non-incretin anti-obesity peptide"in the international top academic journalNature.The study utilized AI algorithms to develop a peptide predictor called"Peptide Predictor,"successfully mapping 2,683 peptides generated by prohormone convertase cleavage that had not been fully characterized before.From this,they identified a novel bioactive peptide composed of only 12 amino acids—BRP(BRINP2-related peptide).To everyone's delight,BRP demonstrated effects on appetite suppression and weight reduction comparable to semaglutide,but without the common side effects associated with GLP-1 class drugs like semaglutide,bringing new hope to the field of weight loss treatment.
Prohormones are precursors of hormones,typically existing as inactive protein states that need to be processed by specific enzymatic cleavage,such as being cut into smaller peptide fragments,to become mature hormones with biological activity.These mature hormones then regulate complex biological processes,including energy metabolism in the brain and other organs.Each prohormone can be decomposed in various ways to produce a large number of functional peptide products,but only a few peptides can act as hormones.Traditional protein separation methods have difficulty isolating peptide hormones from the numerous natural by-products generated during protein degradation and processing,posing a significant challenge to related research.
In this study,Katrin Svensson's team focused on prohormone convertase 1/3(PCSK1/3),an enzyme that can cleave prohormones at specific amino acid sequences and is known to be closely related to human obesity.One of the peptide products is the well-known glucagon-like peptide-1(GLP-1),which regulates appetite and blood sugar levels.The widely used weight loss drug semaglutide works by mimicking the effects of GLP-1 in the body.
Unlike previous approaches,the research team did not use the traditional method of manually separating proteins and peptides from tissues and identifying hundreds of thousands of peptides using mass spectrometry.Instead,they cleverly employed artificial intelligence(AI)technology.They designed the"Peptide Predictor"AI algorithm to identify typical prohormone convertase cleavage sites in approximately 20,000 human protein-coding genes.The corresponding author of the paper emphasized that the AI algorithm played a crucial role in this study,and without AI,such a groundbreaking achievement would have been nearly impossible.
Subsequently,the research team narrowed down the screening scope to genes encoding proteins secreted outside the cell,as secretion outside the cell is a key characteristic of hormones,and these genes have four or more potential prohormone convertase cleavage sites.In this way,they successfully reduced the screening scope to 373 prohormone proteins.Peptide Predictor predicted that PCSK1/3 would generate 2,683 unique peptides from these 373 prohormone proteins.The research team focused on peptide sequences that might have biological activity in the brain and screened 100 peptides(5-25 amino acids in length),including GLP-1,to test their ability to activate cultured neuronal cells in the laboratory.
As expected,GLP-1 significantly affected the neuronal cells,increasing their activity threefold compared to control cells.However,surprisingly,a peptide composed of only 12 amino acids—BRP—increased neuronal cell activity tenfold compared to control cells.BRP is named after the BRINP2 protein from which it originates.
Next,the research team tested the effects of BRP in lean mice and mini pigs(whose metabolism and dietary patterns are closer to humans than mice).The experimental results showed that intramuscular injection of BRP in these two animal models before feeding reduced their food intake by up to 50%in the following hour.Obese mice that received daily BRP injections for 14 consecutive days lost an average of 3 grams in weight,almost entirely fat,while the control group of mice gained about 3 grams during the same period.Moreover,mice treated with BRP also showed improved glucose levels and insulin tolerance.Behavioral studies on mice and pigs found no changes in activity,water intake,anxiety-like behavior,or defecation after treatment.Further physiological and brain activity research indicated that the metabolic and neural pathways activated by BRP are completely different from those activated by GLP-1 class drugs(such as semaglutide).Mechanistically,BRP triggers central FOS activation,that is,it activates neurons in the hypothalamic brain regions related to appetite and metabolism,independently of leptin,GLP-1 receptors,and melanocortin 4 receptors.
Katrin Svensson pointed out that the receptors targeted by semaglutide are not only present in the brain but also in other tissues such as the intestines and pancreas,which explains its broad effects,including slowing down the movement of food in the digestive tract and lowering blood sugar levels.In contrast,BRP seems to act only in the hypothalamus,which controls appetite and metabolism,perhaps explaining why it does not have the common side effects of GLP-1 class drugs like semaglutide.
Currently,the research team is planning to further identify the cell surface receptors that bind to BRP and to deeply analyze its mechanism of action.They are also exploring ways to prolong the duration of BRP's effects in the body so that,once confirmed to effectively regulate human body weight,a more long-acting dosing regimen can be developed.In addition,Katrin Svensson has founded a company called Merrifield Therapeutics,which plans to conduct clinical trials in humans in the near future,bringing new breakthroughs and hope to the field of obesity treatment.
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