A team of researchers has identified common epigenetic mechanisms in researchers and humans related to food addiction. The article, published in the Journal of Clinical Investigation, was led by Rafael Maldonado and Elena Martín, from the Neuropharmacology-Neurophar research group of the UPF Fabra and attached to the Hospital de la Mar Institute for Medical Research (IMIM), and José Manuel Fernández-Real, from the Nutrition, Eumetabolism and Health group of the Institute for Biomedical Research of Girona Dr. Josep Trueta Josep Trueta (IDIBGI) and CIBEROBN.
Food addiction is related to a loss of intake control that is associated with obesity and eating disorders. It is a chronic, multifactorial and complex brain disorder resulting from the interaction of multiple genes and environmental factors. Its prevalence is increasing worldwide and there are no effective treatments.
In a previous article, researchers identified the neurobiological mechanisms that enable the development of food addiction behavior. Specifically, they identified the involvement of certain cortical areas in the brain in the loss of control over eating.
"Once the mechanism was identified, we asked ourselves why there are individuals who are resilient, while others are addicted. To do this, we focused on epigenetic factors, i.e. those external factors, from the environment, that modify gene expression," explains Elena Martín.
The scientists selected extreme populations of rodents addicted and not addicted to food. Specifically, they looked for epigenetic marks in the areas of the cerebral cortex related to this addiction. Among the different epigenetic mechanisms that exist, in this case, they focused on microRNAs, which are small RNA molecules that regulate gene expression in a complex and dynamic way.
On the other hand, they also examined circulating microRNAs in healthy volunteers and passed a questionnaire that is an instrument to measure the degree of food addiction. "What was most fascinating was that the same microRNAs that were affected in the mouse brain were also found to be altered in human plasma. Intriguingly, the same microRNAs were associated with the degree of food addiction quantified by this questionnaire," explains José Manuel Fernández-Real.
Bru Cormand and Noèlia Fernàndez, from the University of Barcelona, the Institute of Biomedicine of the University of Barcelona (IBUB), the Sant Joan de Déu Research Institute (IRSJD) and CIBERER explain that "the main microRNAs identified are involved in processes relevant to food addiction, such as lipid and carbohydrate digestion, morphological changes in the brain, insulin resistance or even addiction to certain substances, such as methamphetamines".
Within this multifactorial disease with multiple expressions, they have identified two main components of behavioral alteration: high motivation for food, and compulsive seeking despite the negative effects of this behavior. "Interestingly, we have seen that two specific epigenetic changes appear to be responsible for these behavioral components of the disease," details Rafael Maldonado. "The similarities between the results in mice and humans give the study important translational value. The role of epigenetics in the vulnerability to food addiction opens the door to the identification of biomarkers for early diagnosis of the disease and to the investigation of future therapies by modifying miRNA expression," he concludes.
The researchers Alejandra García Blanco, Laura Domingo-Rodriguez, Judit Cabana Domínguez and Noèlia Fernàndez-Castillo are the first authors of the article. Scientists from the Center for Biomedical Research Network Physiopathology of Obesity and Nutrition (CIBEROBN), Center for Biomedical Research Network on Rare Diseases (CIBERER), Sant Joan de Déu Research Institute, Center for Genomic Regulation, Vilnius University (Lithuania), University College Cork (Ireland) and the Teagasc Food Research Centre (Ireland) have also participated in the work.
Reference article: García-Blanco A et al. MicroRNAs signatures associated with vulnerability to food addiction in mice and humans. J Clin Invest. 2022.