Molecule with anti-obesity action is successfully tested in animals

A study conducted at the University of São Paulo (USP) showed that a synthetic molecule called Pep19 acts on the endocannabinoid system, which plays an important role in controlling metabolism, regulating appetite, lipolysis (breakdown of fat) and releasing energy.

Recently published in the International Journal of Molecular Sciences, the work was supported by Fapesp and the participation of researchers from the Federal University of Santa Catarina (UFSC), University of Malaga (Spain), Biomedical Research Center for Diabetes and Associated Metabolic Diseases (Spain). ) and the company Proteimax BioTechnology (Israel).

It is not new that scientists are working on ways to influence the functioning of the endocannabinoid system to help people lose weight. In 2008, a drug called rimonabant was used for this purpose, but its sale ended up suspended in Brazil due to serious side effects, such as anxiety and depression, in some cases with a suicidal tendency.

Since then, studies have been carried out to discover safer ways to turn the endocannabinoid system into an ally for those who need to lower the scales. And Pep19 – short for DIIADDEPLT peptide – is one of the big bets in this area, as it has already shown good results in animal tests without interfering with the central nervous system, which would cause side effects similar to those of rimonabant.

Promising performance

In the recently released study, researchers created a synthetic version of a peptide naturally found in human cells. Pep19 is chemically identical to the natural peptide, but can be used in more effective concentrations for the desired purpose. The molecule was then tested on 50 mice, which were divided into two groups. One of them was fed a normal diet for 30 days. The other received high-calorie food. Half of the animals in each group received a saline solution and the other half a saline solution with diluted Pep19.

The results of the experiment were very encouraging. The rodents that received the most caloric diet accompanied by Pep19 had attenuated weight gain and decreased insulin resistance – a phenomenon that can lead to problems such as type 2 diabetes and hypertension, among others. In addition, the molecule reduced inflammation in the liver, the accumulation and distribution of fat in the organ and the activity of alanine aminotransferase, a substance that indicates liver damage.

Another benefit noted by the researchers was that the synthetic peptide turned part of the white fat (which serves as an energy reserve for the body) into brown, which is very positive since it has a thermogenic function, that is, it burns calories to generate energy and heat. , stimulating the weight loss process.

“This process is related to the activation of a type of protein that uncouples the respiratory chain, known by the acronym UCP1. White fat normally does not produce this substance, unlike brown fat”, says Emer Suavinho Ferro, a professor at the Institute’s Pharmacology Department. of Biomedical Sciences (ICB-USP) and responsible for the Intracellular Peptides Pharmacology Laboratory of the institution, who participated in the analysis. “And we could be sure of this relationship when we visually analyzed the fat of the animals and saw that part of it had a beige tone, and thus we had the indication that Pep19 induced the activation of UCP1”, he explains.

According to Ferro, in animals, the gains offered by the use of Pep19 were not accompanied by side effects as in the case of rimonabant. “Its action is peripheral and does not happen directly on the central nervous system,” he explains.

The group now intends to do new work, including in humans, to try to transform this molecule into a viable option for those who need to lose weight.

The investigation is supported by Fapesp through two projects (16/04000-3 and 19/25943-1).