Obesity has become one of the main enemies of health in advanced societies and, therefore, a priority objective for the biomedical community. One of its approaches to combat it is to regulate, with pharmacological help, the levels of ghrelin, also known as “the hunger hormone” , a peptide that is generated mainly in the stomach walls and is directly related to the sensation of appetite – such as have shown different studies with MRIs in the brains of volunteers – and the accumulation of fat.
Experts believe that a good option for overweight people to reduce their excessive food intake is to block the bond of ghrelin with its receptors, which would reduce the desire to eat. The problem is that both the hormone and these receptors perform other important functions in the body, such as the stimulation of growth hormone or the regulation of metabolism and mood. For this reason, drugs to put ghrelin in “off mode” – several have already been developed in recent years, some based on cannabinoids – have undesirable side effects .
Selective treatment
A new study published in the journal Proceedings of the National Academy of Sciences (PNAS) offers hope that a ghrelin-inhibiting pill will finally be designed without the potential collateral damage. The work, developed jointly by scientists from the universities of Copenhagen (Denmark) and Montreal (Canada), focuses on selectively blocking biochemical signaling between the hormone and its receptors to reduce only the sensation of appetite and preserve the rest of the functions.
Specifically, they have focused on a metabolic pathway in which the GQ / 11 protein is involved, directly responsible for increasing the desire to eat. Researchers have observed, for example, that a molecule – called YIL781 – activates the metabolic action of GQ / 11 through experiments on mice.
The trial consisted of administering YIL781 to animals genetically modified so that they were incapable of producing GQ / 11 and to other normal specimens: while the former showed no signs of being hungrier, the latter tripled, on average.
Although, in reality, YIL781 produces the opposite effects to those sought, those responsible for the finding believe that this opens a door to create an effective anti-obesity drug , since they have shown that ghrelin receptors are susceptible to be selectively manipulated.
More information: “Translating biased signaling in the ghrelin receptor system into differential in vivo functions,” by Franziska Mende, Michel Bouvier, and others. October 2018. PNAS (Proceedings of the National Academy of Sciences). https://doi.org/10.1073/pnas.1804003115
