Scientists at Stanford Medicine have identified a natural molecule that reduces appetite and body weight in animal tests. The peptide, called BRP, acts in a more targeted way than semaglutide, the active ingredient in Ozempic, and avoided several common side effects in the experiments carried out.
The discovery paves the way for obesity treatments with a distinct mechanism. Pesquisadores tested BRP in mice and minipigs. The results indicate a significant reduction in food intake without causing nausea, constipation or loss of muscle mass.
Use of artificial intelligence in peptide identification
The team developed a computational tool called Peptide Predictor. The algorithm analyzed human protein-coding genes to locate prohormones that could generate active peptides.
The researchers focused their search on secreted proteins with specific cleavage points associated with an enzyme linked to obesity. Isso Narrowed down thousands of possibilities to 373 candidate prohormones.
From there, the system predicted more than 2,600 potential peptides. The team selected 100 of them for testing on brain cells grown in the laboratory. A small peptide, composed of 12 amino acids, stood out for strongly increasing neuronal activity.
- BRP is derived from the prohormone BRINP2
- It has 12 amino acids in sequence
- Acts mainly on the hypothalamus
- Activates distinct groups of neurons
The peptide was named BRP in reference to its precursor molecule. Testes confirmed that it operates through different biological pathways than GLP-1, which semaglutide mimics.
Assistant Professor of Pathology Katrin Svensson led the study as senior author. Senior researcher Laetitia Coassolo served as lead author. Svensson is also a co-founder of a company planning human clinical trials.
Results in tests with lean and obese animals
A single injection of BRP before feeding reduced food consumption by up to 50% over the next hour in lean mice and minipigs. Minipigs serve as a closer model of human metabolism than mice.
In obese mice, daily injections for 14 days resulted in an average loss of 3 grams of weight, almost all of it from fat. Animais of the control group gained about 3 grams in the same period.
The researchers also observed improvements in glucose and insulin tolerance in the treated animals. Não There were changes in movements, water intake or behaviors indicative of anxiety. Digestion also remained normal.
Long paragraphs allowed us to detail these findings because they involve multiple developments of the experiments. The specific action on the hypothalamus explains why BRP avoids impacts on other tissues, unlike medications that reach receptors in the intestine, pancreas and other areas.
Tests have shown that BRP does not induce food aversion or significantly affect muscle mass. Esses points represent potential advantages over current treatments available for weight control.
Mechanism of action different from semaglutide
Semaglutide activates receptors present in the brain, but also in the intestine and pancreas. Isso generates broad effects, such as slowing gastric emptying and reducing blood sugar levels.
In contrast, BRP appears to act more precisely in the hypothalamus, a region that regulates appetite and metabolism. Ele activates different neurons and follows a related but distinct biological pathway.
This selectivity can reduce unwanted side effects. Researchers continue to investigate the exact receptors that interact with BRP to better understand how it works in the body.
Collaboration between institutions and next steps
The work included the participation of scientists from Universidade, Califórnia, Berkeley, Universidade, Minnesota, and Universidade, Colúmbia Britânica. The funding involved Institutos Nacionais from Saúde from Estados Unidos and other programs from Califórnia0, in addition to entities such as Califórnia1 from Califórnia2.
Svensson and Coassolo appear as inventors on patents relating to the use of BRP peptides for metabolic disorders. The team is now looking to expand the effects of the molecule to make it more practical for future applications, if it proves effective in humans.
The authors highlight that the lack of effective options to treat obesity has persisted for decades. Eles express interest in evaluating the safety and efficacy of BRP in human clinical trials.
Technical details of the peptide and discovery
BRP consists of a specific sequence of 12 amino acids. Ele arises from the cleavage of a larger protein by enzymes called prohormone convertases.
Tool Peptide Predictor focused on typical cleavage sites of this enzyme to map promising candidates. The process made it possible to identify peptides that traditional laboratory methods would have difficulty detecting among inactive fragments.
- Initial analysis covered 20,000 human genes
- Focus on secreted proteins with multiple cleavage points
- Tests on brain cells confirmed high BRP activity
- Direct comparison with GLP-1 showed superior response in neurons
The study was published in the journal Nature. Ele introduces a computational method to discover new bioactive peptides with therapeutic potential.
