Obesity rates have more than doubled in adults and quadrupled in adolescents since 1990, making it a leading cause of noncommunicable diseases (NCDs) such as cardiovascular disease, diabetes, cancer, neurological disorders, chronic respiratory diseases, and digestive disorders. This growing global health crisis calls for effective obesity treatments to reduce the burden on healthcare systems.
Semaglutide, the weekly injectable drug better known by its brand names Ozempic and Wegovy, was initially approved for diabetes treatment but has since transformed the weight-loss industry. However, side effects like nausea and loss of muscle mass — rather than targeted fat reduction — may discourage long-term use or prevent some individuals from starting treatment altogether.
Now, researchers from Stanford Medicine have identified a naturally occurring molecule that mimics semaglutide’s effects but appears to avoid these drawbacks in a study recently published in Nature. This discovery could pave the way for an alternative approach to regulating body weight.
Small Molecule, Big Impact
The study used artificial intelligence to screen more than 2,600 previously uncharacterized human protein fragments in search of novel bioactive compounds. This method is more efficient than traditional approaches that involve manually isolating proteins and peptides from tissues using techniques like mass spectrometry.
Using this AI-driven strategy, the team identified a small peptide composed of just 12 amino acids, the building blocks of proteins, and named it BRINP2-related peptide (BRP). They focused on proteins that interact with enzymes linked to human obesity and are encoded by gene sequences likely to be biologically active in the brain.
“The algorithm was absolutely key to our findings,” said Katrin Svensson, assistant professor of pathology and senior author of the study, in a press release.
Testing the newly discovered molecule on mice and miniature pigs showed that injecting it before feeding reduced food intake by up to 50 percent. The treated obese mice experienced significant weight loss (primarily from fat) along with improved glucose and insulin tolerance compared to the control group. These effects were comparable to those of semaglutide treatment.
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New Molecule Directly Targets the Brain
Semaglutide works by mimicking GLP-1, a hormone that helps regulate blood sugar levels and appetite.
Further physiological and brain activity studies revealed that BRP activates metabolic and neuronal pathways distinct from those triggered by GLP-1 or semaglutide. Instead of stimulating the same receptors, BRP appears to target different neurons in the brain, potentially offering a more precise mechanism for body weight reduction.
“The receptors targeted by semaglutide are found not only in the brain but also in the gut, pancreas, and other tissues,” Svensson explained. “That’s why Ozempic has widespread effects, including slowing digestion and lowering blood sugar levels. In contrast, BRP appears to act specifically in the hypothalamus, which controls appetite and metabolism.”
Additional behavioral studies in mice and pigs showed no significant changes in movement, water intake, anxiety-like behavior, or fecal production among treated animals — suggesting that BRP could avoid the common side effects associated with current weight-loss medications.
Ozempic and Wegovy’s New Competitor?
“The lack of effective drugs to treat obesity in humans has been a problem for decades,” Svensson said in a statement. “Nothing we’ve tested before has compared to semaglutide’s ability to decrease appetite and body weight. We are very eager to learn if it is safe and effective in humans.”
As their research progresses, the team is working to identify the precise receptors BRP interacts with and to gain a deeper understanding of the molecular pathways it influences. Additionally, they are exploring strategies to enhance BRP’s stability in the body, which could enable longer-lasting effects and a more convenient dosing schedule if the molecule proves viable for human weight management.
Overall, this research introduces a promising method for identifying new bioactive proteins and offers hope for BRP’s future pharmacological application in weight management therapy.
Read More: Ozempic and Other GLP-1s May Have Broader Health Benefits but Greater Risks
Article Sources
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Having worked as a biomedical research assistant in labs across three countries, Jenny excels at translating complex scientific concepts – ranging from medical breakthroughs and pharmacological discoveries to the latest in nutrition – into engaging, accessible content. Her interests extend to topics such as human evolution, psychology, and quirky animal stories. When she’s not immersed in a popular science book, you’ll find her catching waves or cruising around Vancouver Island on her longboard.
