AI Helped Find "Natural Ozempic"

Drugs based on semaglutide, such as "Ozempic," have revolutionized the treatment of obesity. They help reduce appetite and body weight but can cause side effects — nausea, difficulty with bowel movements, and other digestive problems. Additionally, during weight loss, a person may lose not only fat but also muscle mass.

Semaglutide mimics the action of the natural hormone GLP-1, which is involved in regulating appetite and blood sugar levels. However, the receptors it acts upon are located not only in the brain but also in the intestines, pancreas, and other organs. Therefore, the drug's action is not limited to suppressing the feeling of hunger.

GLP-1 belongs to the group of peptide hormones. They are formed when special enzymes break down large protein molecules into smaller fragments — peptides. Some of these fragments become hormones that regulate various processes in the body, including metabolism and appetite.

The problem is that a huge number of peptides can be formed during protein breakdown. Determining which of them have important biological functions and which are simply byproducts of decomposition is extremely difficult.

As reported by Science Daily, researchers from Stanford University decided to search among them for new substances capable of regulating appetite. They focused on an enzyme involved in the formation of GLP-1 and other peptide hormones.

To avoid testing hundreds of thousands of potential molecules individually, scientists developed an artificial intelligence algorithm called Peptide Predictor. It analyzed about 20,000 human genes encoding proteins and helped identify 373 proteins from which 2,683 different peptides could be formed.

From these, the researchers selected a hundred substances for laboratory tests, including the already known hormone GLP-1. The scientists tested how these molecules affect the activity of nerve cells.

The most interesting result came from a previously unknown peptide of only 12 amino acids, named BRP (BRINP 2-related peptide). It increased the activity of nerve cells tenfold compared to control samples. For comparison, GLP-1 increased it threefold.

But can BRP not only activate neurons but also influence appetite?

What the studies showed

To test this, scientists administered BRP to mice and miniature pigs. The latter more accurately reflect human metabolism and eating habits than mice. Within an hour of injection, the animals ate up to 50% less food than usual.

In the next experiment, obese mice received the drug daily for two weeks. During this time, they lost an average of three grams of weight, whereas mice in the control group, conversely, gained about three grams. Almost all of the lost weight was fat, not muscle. The animals also showed improved glucose uptake and insulin response.

It is particularly interesting that the researchers found no significant changes in motor activity, water consumption, anxiety-related behaviors, or intestinal function.

Perhaps the reason is that BRP acts differently from semaglutide. According to the researchers, the molecule primarily affects the hypothalamus — a small part of the brain involved in regulating hunger and metabolism. Moreover, it activates different neural mechanisms than GLP-1. Such a more selective action could theoretically help avoid some of the side effects typical of existing weight loss drugs.

What's next?

However, BRP has only been tested on animals so far. It is unknown whether the molecule will be as effective in reducing appetite in humans and whether it truly causes fewer side effects.

Scientists also need to figure out exactly which cellular receptors BRP interacts with and how to prolong the molecule's action in the body. Peptides can break down quite quickly, so without further development, the drug might need to be administered too frequently.

The researchers are already preparing the next stage — human trials. Only these will show whether BRP can become a true alternative to Ozempic.

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