Synthetic peptide acts on endocannabinoid system to combat obesity

An international team of researchers experimenting with the function of the endocannabinoid system have shown how it can be manipulated to combat obesity with the help of a synthetic peptide. The studies carried out on mice demonstrate how the treatment can prevent weight gain and keep diabetes at bay even on high-fat diets, and that it has the capacity to convert white fat into a more desirable brown form.

Discovered in the 1990s via research into the effects of cannabis on the human brain, the endocannabinoid system is a biological system that produces versions of the active constituents in cannabis. Research since has shown how these endocannabinoids can play a role in everything from reducing inflammation, to tackling depression, to shaping the gut microbiome.

The influence of the endocannabinoid system also extends to our metabolism, impacting our appetite, the way we break down fat and our energy expenditure. Scientists have been exploring ways this system might be manipulated to counter obesity and its many related effects on our health, and one promising approach concerns a peptide called Pep19 (DIIADDEPLT).

This is a synthetic and chemically identical version of a peptide that occurs naturally in human cells, but by delivering it in higher doses scientists have shown in animal trials it can benefit metabolic health without any adverse effects on the central nervous system.

In the new study, scientists in Brazil, Spain and Israel treated 50 mice with the peptide across 30 days, half of which were fed a standard diet and the other half a high-fat diet. Despite this unhealthy eating regime, the latter group put on little weight and showed reduced resistance to insulin, a hallmark of type 2 diabetes. The peptide also reduced inflammation, fattiness and signs of damage in the liver.

Interestingly, the team found that it also transformed some of the fat in the mice. White fat is the undesirable type that stores excess energy, and the scientists found the peptide was transforming some of this into brown fat, which helps us stay lean by burning calories to generate heat and keep us warm.

“This process is associated with activation of a type of respiratory chain uncoupling protein known as UCP1,” said study author Emer Suavinho Ferro, from the University of São Paulo’s Biomedical Sciences Institute. “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 scientists are looking to build on these promising findings with further experiments in animals, and plan to carry out trials on human subjects to eventually bring the peptide treatment closer to clinical use.

The research was published in the International Journal of Molecular Sciences.

Source: FAPESP via MedicalXpress

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