An international team of researchers experimenting with the function of the endocannabinoid system has shown how it can be manipulated to fight obesity using a synthetic peptide. Studies in mice show how the treatment can prevent weight gain and prevent diabetes even on high-fat diets, and that it can convert white fat into the more desirable brown form.
The endocannabinoid system, discovered in the 1990s through studies of the effects of cannabis on the human brain, is a biological system that produces versions of the active components of cannabis. Since then, research has shown that these endocannabinoids may play a role in everything from reducing inflammation to fighting depression to shaping the gut microbiome.
The influence of the endocannabinoid system also extends to ours metabolism, affecting our appetite, the way fat is broken down and energy expenditure. Scientists are exploring ways to manipulate this system to combat obesity and its many associated health effects, and one promising approach involves a peptide called Pep19 (DIIADDEPLT).
It 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 studies that it can promote metabolic health without any negative effects on the central nervous system.
In the new study, scientists from Brazil, Spain and Israel treated 50 mice with the peptide for 30 days, half of which were fed a standard diet and the other half – a high-fat diet. Despite this unhealthy eating pattern, the latter group gained little weight and showed reduced insulin resistance, a hallmark of type 2 diabetes. The peptide also reduced inflammation, fat, and signs of liver damage.
Interestingly, the team found that it also transformed some of the fat in the mice. White fat is the unwanted type that stores excess energy, and scientists have discovered that the peptide turns 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 the activation of a type of protein that uncouples the respiratory chain known as UCP1,” said study author Emer Suavinho Ferro of the Biomedical Sciences Institute of the University of São Paulo. “White fat doesn’t normally produce the substance, but brown fat does. We further confirmed the connection in a visual analysis of animal fat. We saw that part of the beige showing that Pep19 led to the activation of UCP1”.
Scientists aim to build on these promising findings with further animal experiments and plan to conduct human trials to eventually bring peptide treatment closer to clinical use.