AI Helps Scientists Discover a Natural Peptide That May Mimic Ozempic Without Key Side Effects

Researchers at Stanford Medicine have identified a naturally occurring peptide that suppresses appetite and promotes weight loss in animals through a mechanism similar to GLP-1 drugs such as semaglutide (Ozempic), but without several of the treatment's most common side effects. The findings were published in Nature.

The newly discovered molecule, called BRP (BRINP2-related peptide), was identified using an artificial intelligence algorithm designed to search the human proteome for previously unknown biologically active peptides.

Unlike semaglutide, which activates GLP-1 receptors found throughout the body—including the brain, gastrointestinal tract, and pancreas—BRP appears to act primarily in the hypothalamus, the brain region responsible for regulating appetite and energy balance. This more targeted mechanism could potentially reduce unwanted effects such as nausea, constipation, and muscle loss.

To identify the peptide, researchers developed an AI-based tool called Peptide Predictor, which analyzed approximately 20,000 human protein-coding genes. The algorithm identified proteins likely to generate biologically active peptide hormones, narrowing thousands of candidates to 373 prohormones capable of producing 2,683 potential peptides.

Laboratory testing revealed one previously unknown peptide consisting of only 12 amino acids that strongly activated neurons involved in appetite regulation. The researchers named the peptide BRP.

The team then evaluated BRP in lean mice and minipigs. A single intramuscular injection administered before feeding reduced food intake by up to 50% during the following hour in both species.

In obese mice treated with daily BRP injections for 14 days, body weight decreased by an average of 3 grams, with nearly all of the weight loss resulting from reduced body fat. In contrast, untreated animals gained approximately 3 grams over the same period. The treated mice also showed improved glucose tolerance and insulin sensitivity.

Importantly, the researchers did not observe several adverse effects commonly associated with GLP-1 receptor agonists. The animals showed no evidence of reduced physical activity, increased anxiety, decreased water intake, constipation, or nausea-related behaviors. Significant muscle loss, another concern with current weight-loss medications, was also not detected.

Further experiments suggested that BRP activates neural circuits distinct from those targeted by GLP-1, indicating that appetite suppression may occur through a different biological pathway.

Although the results are promising, the researchers emphasize that the findings are currently limited to animal studies. Future work will focus on identifying the receptor through which BRP acts, understanding its signaling mechanisms, and modifying the peptide to extend its duration of action before human clinical trials begin.

If future studies confirm its safety and effectiveness in humans, BRP could represent a new class of anti-obesity therapy that offers meaningful weight loss with fewer gastrointestinal and metabolic side effects than existing GLP-1-based medications.

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