Weight loss is encouraged by a naturally occurring molecule that suppresses appetite.
Researchers from Stanford Medicine have discovered a naturally occurring molecule that functions similarly to semaglutide, commonly marketed as Ozempic, in terms of appetite suppression and weight loss. Interestingly, studies conducted on animals also revealed that it was effective without some of the negative effects of the medication, including nausea, constipation, and a marked loss of muscle mass.
The recently identified molecule, BRP, appears to provide a more focused method of body weight loss by activating distinct neurons in the brain and acting through a different but comparable metabolic pathway. In addition to the brain, semaglutide also targets receptors in the pancreas, gut, and other tissues. Because of this, Ozempic has a variety of effects, such as lowering blood sugar levels and slowing the passage of food through the digestive system. BRP, on the other hand, seems to have a specific effect on the hypothalamus, which regulates metabolism and appetite.
Without using artificial intelligence to sort through dozens of proteins in a class known as prohormones, the study would not have been feasible. Prohormones are physiologically inert molecules that become active when other proteins break them down into smaller molecules known as peptides. Some of these peptides then act as hormones to control intricate biological processes in the brain and other organs, such as energy metabolism.
Numerous functional peptide progeny can be produced by splitting each prohormone in different ways. However, it is challenging to separate peptide hormones which are comparatively uncommon from the biological soup of the far more common natural byproducts of protein processing and degradation using conventional protein isolation techniques. The prohormone convertase 1/3, which is known to play a role in human obesity, was the focus of the study. It separates prohormones at particular amino acid sequences. Glucagon-like peptide 1, or GLP-1, is one of the peptide products that control blood sugar and appetite; semaglutide functions by simulating GLP-1’s physiological effects. To find additional peptides involved in energy metabolism, the team looked to artificial intelligence.
Peptide predictor
The researchers created a computer algorithm they called Peptide Predictor to find common prohormone convertase cleavage sites in all 20,000 human protein-coding genes, eliminating the need to manually separate proteins and peptides from tissues and use methods like mass spectrometry to identify hundreds of thousands of peptides. They then concentrate on genes that encode proteins with four or more potential cleavage sites and that are secreted outside of the cell, which is a crucial feature of hormones. By doing this, the search was reduced to 373 prohormones, which is a manageable quantity to check for biological effects.
Prohormone convertase 1/3 was expected to produce 2,683 distinct peptides from the 373 proteins, according to Peptide Predictor. Coassolo and Svensson concentrated on sequences that the brain is probably biologically active. They tested 100 peptides, including GLP-1, for their capacity to stimulate neuronal cells cultured in a lab. The GLP-1 peptide, as anticipated, had a strong effect on the neurons, causing them to become three times more active than the control cells. However, a tiny peptide consisting of only 12 amino acids increased the cells’ activity ten times more than controls. Based on its parent prohormone, BPM/retinoic acid inducible neural specific 2, also known as BRINP2 (BRINP2-related-peptide), the researchers called this peptide BRP.
An intramuscular injection of BRP before feeding decreased food intake over the following hour by up to 50% in both animal models, according to the researchers’ testing of the drug’s effects on lean mice and minipigs, which more closely resemble human metabolism and eating patterns than mice do. Over 14 days, obese mice given daily injections of BRP lost an average of 3 grams, almost entirely as a result of fat loss, whereas control mice gained roughly 3 grams. Additionally, the mice showed enhanced insulin and glucose tolerance.
Behavioral studies of the pigs and mice revealed no differences in the fecal production, water intake, anxiety-like behavior, or movement of the treated animals. Additionally, additional research on brain and physiological activity revealed that BRP activates metabolic and neuronal pathways independently of those triggered by semaglutide or GLP-1. In addition to further deconstructing the mechanisms of action of BRP, the researchers aim to identify the cell-surface receptors that bind it. If the peptide is successful in controlling human body weight, they are also looking into ways to prolong its effects on the body so that a more convenient dosing schedule can be used.
According to Svensson, the dearth of efficient medications to treat obesity in people has existed for many years. The ability of semaglutide to reduce appetite and body weight is superior to anything we have tested previously. We are very interested in finding out if it works and is safe for people. The study included contributions from researchers at the University of British Columbia, the University of Minnesota, and the University of California, Berkeley.
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