Brazilian scientists have demonstrated that a new peptide has powerful anti-obesity properties in a rodent study and may help develop a potent weight loss drug.
In a mouse model study conducted at the University of São Paulo (USP), researchers have shown that a synthetic molecule – known as Pep19 – effectively influences the endocannabinoid system, which is essential for regulating and balancing metabolic processes, such as appetite, fat breakdown (lipolysis), and energy release.
The search for a weight loss drug
Researchers have long searched for an efficacious way to influence the endocannabinoid system to help people manage their weight. In 2006, scientists believed they had made a breakthrough with the development of a weightloss drug known as rimonabant that acted as a cannabinoid receptor antagonist.
However, the weight loss drug was swiftly outlawed in Brazil to the array of severe adverse side effects that some patients experienced, including anxiety, depression, and in some serious cases, suicidal tendencies.
Since then, various studies have been performed to design safer methods of harnessing the power of the endocannabinoid system to burn fat. One of the most exciting candidates so far – Pep19 (DIIADDEPLT) – has displayed good tolerability so far in animal trials without causing detrimental effects on the central nervous system.
What is Pep19, and how does it work?
Pep19 is a synthetic version of a peptide that is found naturally in human cells, and although they are chemically identical, Pep19 can be administered at higher doses to achieve more powerful effects.
To test the performance of Pep19, the team examined its effects on 50 mice who were divided into two groups. For 30 days, one group was fed a standard diet and the other a high-fat diet, with Pep19 diluted in saline given to half of each group and saline only to the other half.
The results illuminated that the mice given the high-fat diet and Pep19 only put on a small amount of weight and displayed reduced insulin resistance. Moreover, the peptide decreased liver inflammation and fattiness and inhibited alanine-aminotransferase (ALT) activity, which increases liver damage and is a marker to screen for liver disease.
The scientists also observed that Pep19 converted some of the white fat of the mice into brown fat, which is an exciting finding as brown fat is thermogenic and usually assists in weight loss by burning calories to produce energy and heat.
Emer Suavinho Ferro, the last author of the study and a professor in the Pharmacology Department of the University of São Paulo’s Biomedical Sciences Institute (ICB-USP), commented: “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. 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.”
The team explained that Pep19 did not cause any of the adverse side effects produced by the rimonabant weight loss drug.
Ferro concluded: “Pep19’s action is peripheral and doesn’t directly affect the central nervous system.”
The researchers are now aiming to perform clinical trials of Pep19 in humans to develop the peptide into an effective weight loss drug.