News Release

Peptide with anti-obesity action is successfully tested in animal trial

In mice fed a high-fat diet, the molecule mitigated weight gain while reducing insulin resistance and liver fattiness

Peer-Reviewed Publication

Fundação de Amparo à Pesquisa do Estado de São Paulo

Chemical structure of Pep19

image: Chemical structure of Pep19 view more 

Credit: Researchers’ archive

A study conducted at the University of São Paulo (USP) in Brazil shows that the synthetic molecule Pep19 acts on the endocannabinoid system, which helps regulate and balance key metabolic functions, such as appetite, fat breakdown (lipolysis), and energy release.

An article presenting the results of the study is published in the International Journal of Molecular Sciences. The study was supported by FAPESP and involved collaboration by researchers at the Federal University of Santa Catarina (Brazil), the University of Málaga and the Biomedical Center for Research on Diabetes and Associated Metabolic Diseases (Spain), and Israeli company Proteimax BioTechnology.

Scientists have long sought ways of influencing the functioning of the endocannabinoid system to help people lose weight. Rimonabant, a drug that acted as a cannabinoid receptor antagonist, was launched in 2006 but banned in Brazil owing to severe adverse side effects, including anxiety and depression, with suicidal tendencies in some cases.

Studies have been performed since then to discover safer means to make the endocannabinoid system an ally of people who need to lose weight. Pep19 (DIIADDEPLT) is a novel peptide and one of the leading candidates in this field. It has obtained good results in animal trials without adverse effects on the central nervous system.

Promising performance

According to the recently published article, Pep19 is a synthetic version of a peptide naturally found in human cells. They are chemically identical, but Pep19 can be used in higher doses to achieve the desired effect. The researchers tested it on 50 mice divided into two groups, one fed a standard diet and the other a high-fat diet for 30 days. Pep19 diluted in saline was given to half of each group and saline only to the other half. 

The results of the experiment were highly encouraging. The mice given the high-fat diet and Pep19 put on little weight and exhibited reduced insulin resistance, which can lead to type 2 diabetes and hypertension, among other problems. The molecule also reduced liver inflammation and fattiness, as well as inhibiting alanine-aminotransferase (ALT) activity. ALT increases with liver damage and is used as a marker to screen for liver disease.

Another benefit detected by the researchers was that the synthetic peptide converted part of the organism’s white fat (its energy reserve) into brown fat, which is significant because brown fat is thermogenic, tending to assist weight loss by burning calories to generate energy and heat.

“This process is associated with activation of a type of respiratory chain uncoupling protein known as UCP1. White fat doesn’t normally produce the substance, but brown fat does,” said Emer Suavinho Ferro, last author of the article. Ferro is a professor in the Pharmacology Department of the University of São Paulo’s Biomedical Sciences Institute (ICB-USP) and heads the institution’s Intracellular Peptide Pharmacology Laboratory. “We further confirmed the link in a visual analysis of the animals’ fat. We saw that part of it had become beige, showing that Pep19 led to activation of UCP1.”

According to Ferro, Pep19 benefited the animals without the adverse side effects caused by rimonabant. “Its action is peripheral and doesn’t directly affect the central nervous system,” he said.

The researchers plan to conduct more experiments, including clinical trials involving human patients, in an attempt to make the molecule a viable option for people who need to lose weight.

The investigation is supported by FAPESP via two projects (16/04000-3, and 19/25943-1).

About São Paulo Research Foundation (FAPESP)

The São Paulo Research Foundation (FAPESP) is a public institution with the mission of supporting scientific research in all fields of knowledge by awarding scholarships, fellowships and grants to investigators linked with higher education and research institutions in the State of São Paulo, Brazil. FAPESP is aware that the very best research can only be done by working with the best researchers internationally. Therefore, it has established partnerships with funding agencies, higher education, private companies, and research organizations in other countries known for the quality of their research and has been encouraging scientists funded by its grants to further develop their international collaboration. You can learn more about FAPESP at and visit FAPESP news agency at to keep updated with the latest scientific breakthroughs FAPESP helps achieve through its many programs, awards and research centers. You may also subscribe to FAPESP news agency at






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