Stanford Medicine researchers identify BRP as a naturally occurring alternative to GLP-1s.
Obesity is a major public health challenge. According to the US Centers for Disease Control and Prevention (CDC), approximately 40% of American adults are considered clinically obese. The World Health Organization reports that 1/8 people globally are obese and that “adult obesity has more than doubled since 1990” and that “adolescent obesity has quadrupled.”
While already a serious health concern, obesity also contributes to a range of chronic conditions. This includes diabetes, cardiovascular disease, and even some cancers.
In response, the demand for effective weight-loss therapies has risen. The popularity of glucagon-like peptide-1 (GLP-1) agonists – particularly Novo Nordisk’s Ozempic and Eli Lilly’s Mounjaro/Zepbound – has surged. These drugs mimic the effects of the natural GLP hormone which triggers the feeling of fullness. Through this mechanism, GLP-1s suppress appetite and helps patients to eat less and lose weight.
However, GLP-1-induced weight loss often comes at a cost. The use of such medications has been associated with serious side effects. Ozempic, also known as semaglutide, is reported to cause nausea, abdominal pain, muscular dystrophy, and kidney failure.
Now, researchers at Stanford Medicine have discovered a naturally occurring peptide that rivals the effects of available GLP-1 agonists – without the downsides. The Nature study explores how BRINP2-related peptide (BRP) could offer an alternative for patients struggling with obesity.
Artificial intelligence (AI) played an integral role in the discovery of BRP.
Laetitia Coassolo, lead author, and her colleagues developed an AI tool to identify “novel peptides with pharmacological potential.” Dubbed the Peptide Predictor, this computer algorithm facilitated a complex search of prohormones. These large, soluble proteins are inactive until they’re cleaved by enzymes into peptides.
Typically, identifying functional peptides derived from prohormones can be like finding a needle in a haystack. Each prohormone can produce several peptides, but only a few play a role in regulatory biological functions – in this case, appetite.
To overcome this, the researchers at Stanford reprogrammed the Peptide Predictor to focus on prohormone convertase 1/3 (PC1/3). Studies show that individuals deficient for this enzyme are more likely to be obese. Furthermore, PC1/3 is crucial for the cleavage of proglucagon into the appetite-suppressing GLP-1 hormone.
The team then took the candidate peptides and treated INS1 β-cell and neuronal Neuroscreen-1 (NS1) cell lines. They measure Fos gene expression as a proxy for bioactivity: the more Fos mRNA in the cells after peptide treatm
