Ozempic or semaglutide, which was originally developed to treat type 2 diabetes by mimicking the hormone glucagon-like peptide-1 (GLP-1), has gained widespread use for weight loss. However, it comes with serious side effects, including nausea and muscle loss.
In a recent study published in Nature, Standford University scientists have identified a novel 12-amino acid peptide called BRINP2-related peptide or BRP, that significantly reduces appetite and reverses obesity in mice and pigs.
Unlike existing weight-loss treatments, BRP activates specific brain pathways that control food intake without triggering nausea or aversion, making it a promising candidate for future therapies.
Study: Prohormone cleavage prediction uncovers a non-incretin anti-obesity peptide. Image Credit: MillaF/Shutterstock.com
Weight-Loss Medications
Obesity is a growing global health crisis linked to numerous metabolic diseases, such as diabetes and cardiovascular disorders.
Current weight-loss treatments, including medications like GLP-1 receptor agonists, can be effective but often come with side effects such as nausea, vomiting, and loss of lean muscle mass.
Scientists have long sought alternatives that safely suppress appetite while maintaining metabolic health. Peptide-based therapies have emerged as a promising field due to their ability to target specific physiological pathways with minimal side effects.
However, the identification of new bioactive peptides has been largely limited to natural hormone discovery. A major challenge remains in predicting and designing peptides with therapeutic potential.
The Current Study
To address this challenge, the research team from Stanford University developed a computational tool called Peptide Predictor, which systematically identifies bioactive peptides based on their structural features and post-translational processing patterns.
This approach led to the discovery of BRP, a peptide that reduces appetite and body weight by acting on key neural pathways involved in hunger regulation. After synthesizing BRP, the team tested its effects by administering it to mice and pigs through intraperitoneal injection.
The study involved both lean and diet-induced obese mice. BRP-treated mice were monitored for food intake, body weight, and metabolic responses over two weeks.
The researchers measured food consumption using metabolic cages and analyzed physiological responses such as glucose tolerance and fat distribution. Additionally, histological analysis was performed on key metabolic tissues, including white adipose tissue, brown adipose tissue, liver, and skeletal muscle.
To explore the neural mechanisms underlying BRP’s effects, the study also included brain activation studies that assessed FOS protein expression, a marker of neuronal activity. In a parallel study with pigs, the researchers tested BRP’s effects on food intake and body weight over several days.
Major Findings
The results showed that BRP significantly reduces appetite and body weight in both mice and pigs. In diet-induced obese mice, daily administration of BRP led to a marked decrease in food intake, resulting in substantial weight loss within two weeks.
Notably, this weight reduction occurred without inducing aversive reactions, which are commonly associated with many appetite-suppressing drugs.
A key discovery was that BRP activates specific neuronal pathways in the hypothalamus while avoiding nausea-related brainstem circuits. Unlike GLP-1 receptor agonists, which often trigger nausea and gastrointestinal distress, BRP acted centrally on appetite control without causing discomfort.
The researchers found that BRP stimulates the cAMP–PKA–CREB–FOS pathway, which involves various signaling molecules such as cAMP (cyclic adenosine monophosphate), PKA (protein kinase A), CREB (cAMP response element-binding protein), and FOS, in neuronal cells, a mechanism linked to reduced food consumption.
Further analysis revealed that BRP treatment led to decreased fat mass while preserving lean muscle mass, a critical advantage over conventional weight-loss treatments.
Histological examination of metabolic tissues confirmed that BRP administration resulted in reduced fat accumulation in white adipose tissue and improved metabolic function in the liver and skeletal muscles.
In pigs, BRP demonstrated similar appetite-suppressing effects, reducing food intake without affecting overall energy expenditure. This cross-species consistency was promising as it suggested that BRP could be effective in larger mammals, increasing its potential for human applications.
Despite its promising effects, the study acknowledged some limitations. The precise receptor for BRP remains unidentified, and its long-term metabolic effects require further exploration. Additionally, while BRP was effective in inducing weight loss, future studies are needed to assess whether it is necessary for maintaining reduced body weight over extended periods.
Katrin Svensson, the senior researcher for the study, stated, “Nothing we’ve tested before has compared to semaglutide’s ability to decrease appetite and body weight. We are very eager to learn if [BRP] is safe and effective in humans.”
Conclusions
In summary, the findings suggested that BRP was a promising peptide with significant appetite-suppressing and weight-reducing effects.
Unlike existing treatments, BRP achieves these outcomes without nausea or adverse metabolic consequences, making it a compelling candidate for obesity management.
Future research will focus on identifying its receptor, optimizing its therapeutic potential, and evaluating its effects in humans. If successful, BRP could revolutionize weight-loss treatments, offering a safer and more targeted approach to combating obesity.
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