Jack Nash Jack Nash26 July 2022 Open Science
Image for weight loss and Pep19.

Pep19: The Molecule that Meddles with Metabolism

The science of weight loss is big business, as the world wrestles with an obesity epidemic. A team of scientists from the University of São Paulo in Brazil, in collaboration with scientists from the University of Malaga, Spain, have made a novel molecule called Pep19 (DIIADDEPLT). It acts on the system which regulates and balances key metabolic functions, such as appetite, fat breakdown and energy release.

There are multiple contributors responsible for our currently overweight population, such as genetic, behavioural and social factors. Obesity is commonly linked to type 2 diabetes and high blood pressure, often leading to lower life expectancy. Although healthy lifestyle is key to reducing global obesity, research into the biochemistry of obesity is also needed.

The research, published in IJMS, was performed by Silverio et al. Pep19 interacts with the endocannabinoid system, which controls metabolic function. The endocannabinoid system has been a target for weight loss drugs for the past 15 years, however many previous attempts to develop drugs which interact with the cannabinoid receptor have lead to severe side effects, such as anxiety and depression.

What is Pep19?

Pep19 is a synthetic version of a peptide found naturally in animal and human cells. The novel peptide interacts with the endocannabinoid system. Constructed of amino acids, the molecule is structurally identical to a naturally occurring peptide. Pep19 can be used, in conjunction with the naturally occurring molecule, to boost the dosage to achieve weight loss effects.

How Does It Aid Weight Loss?

The study involved 50 mice, fed either a standard or high fat diet for 30 days. Half of the mice from each group was given Pep19, and the other half a placebo. The results of the investigation were encouraging. The mice given the high-fat diet and Pep19 put on little weight compared to the other high-fat group.

The researchers also noted that Pep19 reduced liver inflammation. It also inhibited alanine-aminotransferase (ALT) activity. High levels of ALT can be used as a marker for liver disease.

Another benefit is that Pep19 converted part of the mice’s white fat (its energy reserve) into brown fat. This is significant as brown fat is easier to burn during weight loss. “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, one of the co-authors of the article. Ferro is a professor in the Pharmacology Department of the University of São Paulo’s Biomedical Sciences Institute (ICB-USP) and leads 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.

Pep19 did not cause the same adverse side effects caused by previously discovered weight loss molecules. “Its action is peripheral and doesn’t directly affect the central nervous system,” states Ferro.

The researchers plan to conduct follow-up experiments. This may include clinical trials involving human patients, attempting to make the molecule an option for people wishing to lose weight.