A team of researchers at Stanford Medicine has discovered a naturally occurring molecule, BRP, that may replicate some weight loss effects of the drug semaglutide, known as Ozempic, without the common side effects associated with it.
STANFORD, CA – Researchers at Stanford Medicine have unveiled a naturally occurring molecule that shows promise in mimicking the weight loss effects of semaglutide, commonly referred to as Ozempic, according to a study published in the journal Nature. This discovery could offer a new, more targeted approach to weight management and obesity treatment, potentially leading to effective therapies without the adverse side effects seen in current medications.
In animal studies, the molecule, designated as BRP, demonstrated an ability to significantly reduce both appetite and body weight. Notably, these effects were achieved without several common side effects associated with semaglutide, such as nausea, constipation, and muscle loss. This finding is particularly relevant given the rising rates of obesity and related health complications globally.
Katrin Svensson, PhD, an assistant professor of pathology and the senior author of the study, explained the mechanism behind BRP’s action. “The receptors targeted by semaglutide are found in the brain but also in the gut, pancreas, and other tissues. That’s why Ozempic has widespread effects, including slowing the movement of food through the digestive tract and lowering blood sugar levels,” Svensson noted. “In contrast, BRP appears to act specifically in the hypothalamus, which controls appetite and metabolism.”
Significance of the Discovery
The study’s lead author, senior research scientist Laetitia Coassolo, PhD, emphasized the importance of this research, stating, “The lack of effective drugs to treat obesity in humans has been a problem for decades. Nothing we’ve tested before has compared to semaglutide’s ability to decrease appetite and body weight.” This statement underscores the urgency for new therapeutic avenues in combating obesity, a condition that affects approximately 42% of adults in the United States, according to the Centers for Disease Control and Prevention (CDC).
Artificial Intelligence in Research
The discovery of BRP was significantly aided by artificial intelligence (AI), which played a crucial role in analyzing a vast array of molecules known as prohormones. These molecules are initially inactive but can be processed into smaller peptide fragments that can influence metabolic processes. Identifying functional peptide hormones through traditional laboratory methods is often challenging due to the multitude of inactive fragments generated during protein breakdown.
The research team utilized an AI tool dubbed “Peptide Predictor” to scan all 20,000 human protein-coding genes, identifying potential cleavage points for prohormones. Focusing on an enzyme known as prohormone convertase 1/3, which is linked to obesity, the team narrowed their search to 373 prohormones deemed suitable for further investigation. Ultimately, the algorithm predicted 2,683 possible peptides, of which 100 were selected for testing.
Svensson remarked, “The algorithm was absolutely key to our findings,” highlighting the innovative use of technology in modern biomedical research.
Preliminary Animal Studies
In experiments conducted on lean mice and minipigs—an animal model that more closely resembles human metabolism—BRP was found to significantly reduce food intake. A single injection administered before feeding resulted in a consumption reduction of up to 50% within one hour. In obese mice subjected to daily injections over a 14-day period, an average weight loss of 3 grams was observed, primarily from fat, while untreated mice gained approximately 3 grams during the same timeframe.
Furthermore, treated animals exhibited improvements in glucose and insulin tolerance, without alterations in movement, water intake, anxiety-like behavior, or digestion. These findings suggest that BRP operates through distinct brain and metabolic pathways compared to GLP-1 and semaglutide, potentially positioning it as a safer alternative for weight management.
Future Directions
The research team is now focused on identifying the specific receptors that interact with BRP and understanding its functional mechanisms within the body. They are exploring ways to extend the duration of its efficacy for potential human use. Svensson expressed enthusiasm about the forthcoming phases of research, stating, “We are very eager to learn if it is safe and effective in humans.”
Collaboration and Funding
This research project involved collaboration with scientists from the University of California, Berkeley; the University of Minnesota; and the University of British Columbia. Funding for the study was provided by the National Institutes of Health through multiple grants, as well as support from various Stanford programs, the American Heart Association, the Carlsberg Foundation, and the Wu Tsai Human Performance Alliance. Both Svensson and Coassolo are listed as inventors on patents related to BRP peptides targeting metabolic disorders, and Svensson has co-founded a company, Merrifield Therapeutics, which plans to initiate human clinical trials in the near future.
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