Correlation Between the Presence of COMT Val158Met Polymorphism and Dopaminergic Transporter Density (DAT) in Obese Young Women

The prevalence of obesity remains increasingly alarming in Brazil and worldwide. The most widely recommended therapy for obesity is lifestyle modification, however, implementing these changes that can lead to weight loss is difficult and maintaining a long-term weight loss is even more challenging. Consequently, an academic effort is required to understand the pathophysiology and treat obesity for the establishment of new approaches to reducing food intake.

Recent evidence in the field of obesity and brain-based integration indicates a potential for designing new therapeutic interventions. Noninvasive neuromodulation of brain activity has been shown to be a technique that can help reduce food cravings and food intake and, more recently, body weight, offering a new way to treat obesity. However, recent studies have shown that this biomedical intervention could have a paradoxical effect related to COMT Val158Met polymorphism, which impacts dopamine levels in the prefrontal cortex. The potential mechanisms underlying this effect are unclear and future studies are needed to promote this clarification.

This study aims to verify the influence of the COMT Val158Met polymorphism on the density of dopaminergic transporters in the presynaptic membrane of dopaminergic neurons, exploring the 3 dopaminergic pathways: via nigroestrital, mesolimbic and mesocortical. This investigation will be carried out through the cerebral SPECT using the radiopharmaceutical 99mTecnécio-TRODAT-1 in young obese women with and without COMT Val158Met polymorphism. In baseline conditions, the investigators will compare the SPECT 99mTc-TRODAT-1 of obese women with and without the COMT Val158Met polymorphism with a database of non-obese volunteers.

Our hypothesis is that the study will facilitate understanding of the variability of the individual response of carriers and non-carriers of the Met allele of the COMT Val158Met polymorphism, affecting dopamine levels in the brain and to design, in the future, for the treatment of obesity based on the individuals' genotypic differences.