Stanford Uncovers Nature’s Ozempic — Same Weight Loss, No Side Effects

Stanford Medicine researchers have identified a naturally occurring molecule that suppresses appetite and reduces body weight in a manner similar to semaglutide, commonly known as Ozempic. Animal testing indicates that this molecule, 12-amino-acid BRP peptide, achieves these effects without some of semaglutide’s side effects, including nausea, constipation, and significant muscle loss. BRP operates through a distinct but related metabolic pathway, activating different neurons in the brain. This mechanism suggests a more targeted approach to weight reduction.

Researchers Develop Peptide Predictor to Identify BRP from 20,000 Prohormone-Encoding Genes

A research team led by Stanford Medicine sought to identify a natural alternative to semaglutide that could promote weight loss while minimizing its side effects. Their approach focused on prohormones, biologically inactive protein molecules that become active when broken down into smaller peptides by other proteins. Some of these peptides act as hormones within the body, making them potential candidates for weight-loss treatments.

To identify promising peptides, the researchers developed an algorithm called Peptide Predictor, which analyzed 20,000 prohormone-encoding genes and examined how they could be processed by other proteins. The algorithm predicted that prohormone convertase 1/3 would generate 2,683 unique peptides from 373 proteins. Researchers focused on sequences likely to be biologically active in the brain, screening 100 peptides, including GLP-1, for their ability to activate lab-grown neuronal cells. As expected, GLP-1 showed a robust effect, increasing neuronal activity threefold over control cells. 

However, a small peptide consisting of just 12 amino acids demonstrated an even more powerful effect, boosting neuronal activity tenfold compared to controls. The researchers named this peptide BRP, derived from its parent prohormone, BPM/retinoic acid inducible neural specific 2 (BRINP2). This discovery suggests that BRP may offer a more targeted mechanism for weight regulation, and researchers propose that a drug acting specifically on the brain could provide advantages over Ozempic, which affects the entire body.

“The receptors targeted by semaglutide are found in the brain but also in the gut, pancreas and other tissues,” said assistant professor of pathology Katrin Svensson, PhD. “That’s why Ozempic has widespread effects including slowing the movement of food through the digestive tract and lowering blood sugar levels. In contrast, BRP appears to act specifically in the hypothalamus, which controls appetite and metabolism.”

BRP Reduces Food Intake by 50% and Promotes Fat Loss in Obese Mice While Improving Glucose and Insulin Tolerance 

Since its U.S. release in 2017, the injectable drug Ozempic has helped thousands lose weight while demonstrating a range of health benefits, including potential effects in reducing alcohol addiction, alleviating osteoarthritis-related knee pain, lowering the risk of kidney failure in some type 2 diabetics, and mitigating the cardiovascular risks associated with obesity. However, despite its promise, Ozempic comes with various side effects, from mild symptoms like nausea, diarrhea, and dizziness to more severe conditions such as gallbladder disease, hypoglycemia, and pancreatitis. The drug has also been linked to suicidal ideation and a significantly increased risk of a rare form of blindness known as an “eye stroke.”

Researchers tested the effect of BRP on lean mice and minipigs, which more closely mirror human metabolism and eating patterns than mice. They found that an intramuscular injection of BRP before feeding reduced food intake by up to 50% over the next hour in both animal models. In obese mice treated with daily injections of BRP for 14 days, the animals lost an average of 3 grams, mostly due to fat loss, while control mice gained about 3 grams over the same period. Additionally, the BRP-treated mice showed improved glucose and insulin tolerance.

Behavioral studies on both the mice and minipigs revealed no differences in movement, water intake, anxiety-like behavior, or fecal production between treated and control animals. Further physiological and brain activity studies indicated that BRP activates metabolic and neuronal pathways separate from those activated by GLP-1 or semaglutide. The researchers aim to identify the cell-surface receptors that bind BRP and further explore its mechanisms of action. They are also investigating ways to extend the peptide’s effects in the body to potentially allow for a more convenient dosing schedule if it proves effective in regulating human body weight.

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Denisse Sandoval