What if we tell you that a naturally occurring molecule can do wonders like Ozempic, but without the side effects. Hard to believe, isn't it? However, Stanford Medicine researchers have found a molecule that acts similar to semaglutide, by suppressing appetite and reducing body weight. The trials on animals have also shown that it worked without some of the drug's side effects, including nausea, constipation and significant loss of muscle mass. The paper was published on March 5 in Nature, and led by Laetitia Coassolo, PhD, Kartin Svensson, assistant professor of pathology.What Is This Naturally Occurring Molecule?This newly discovered molecule is BRP. This acts, though, in a separate pathway, but has similar metabolic effects. It can activate different neurons in the brain and offer a more targeted approach to body weight reduction. Stanford Medicine's release quoted Svensson, PhD, who explained, "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. In contrast, BRP appears to act specifically in the hypothalamus, which controls appetite and metabolism.”Svensson has also co-founded a company to launch clinical trials of the molecule in humans in the near future. How Was The Study Conducted?This study would not have been possible without the help of AI, notes the release. Researchers used AI to sift through dozens of proteins in a group called prohormones.Prohormones are molecules that do not do anything on their own at first. They become active only after being cut into smaller pieces, called peptides, by other proteins. Some of these peptides then act as hormones, controlling important functions in the body, such as energy use in the brain and other organs.Each prohormone can be cut in different ways, producing many possible peptides. Among these, only a few actually work as hormones, while most are just byproducts of protein breakdown. Traditional lab methods make it hard to find the useful peptides in this mix.The researchers focused on an enzyme called prohormone convertase 1/3, which cuts prohormones at specific points in the amino acid chain. This enzyme has been linked to obesity in humans. One of the peptides it produces is GLP-1, which helps control appetite and blood sugar levels. The drug semaglutide works by mimicking GLP-1. The team wanted to see if there were other peptides from this enzyme that also play a role in energy metabolism.To do this, they created a computer program called Peptide Predictor. Instead of manually sorting through proteins, the program scanned all 20,000 human protein-coding genes to find likely cutting sites for prohormone convertase 1/3. They focused only on proteins that are secreted outside the cell, a key feature of hormones, and that had at least four cutting sites. This narrowed the list to 373 prohormones.The program predicted that these could produce 2,683 unique peptides. The team then looked at those most likely to act in the brain and tested 100 of them, including GLP-1, on lab-grown nerve cells.GLP-1 increased cell activity about three times compared to normal cells, as expected. But one small peptide, just 12 amino acids long, increased activity tenfold. They named it BRP, based on the name of its parent protein BRINP2.What Did The Result Reveal?Tests on lean mice and minipigs showed promising results. An injection of BRP before feeding reduced food intake by up to 50% over the next hour. In obese mice, daily injections for two weeks led to an average weight loss of 3 grams, mostly fat, while untreated mice gained about 3 grams. The treated mice also had better blood sugar control.Importantly, BRP did not change the animals’ movement, water intake, anxiety levels, or digestion. It also works through different brain and body pathways than GLP-1 or semaglutide, which could make it useful for people who do not respond well to those drugs.What's Next?Researchers now want to find the exact cell receptors BRP binds to and figure out how to make its effects last longer in the body. If it proves safe and effective in humans, BRP could offer a new option for treating obesity.The study was a collaboration between scientists at the University of California, Berkeley, the University of Minnesota, and the University of British Columbia.
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