Unravelling the hypothalamic epigenetic code behind obesity.
Despite titanic social and scientific efforts, rates of obesity continue to increase in Europe. Unfortunately, safe and effective treatments are currently unavailable. Obesity is a multifactorial disease that is largely the consequence of enigmatic and complex genetic-environmental interactions. Evidence suggests that the prevalent western-diet triggers epigenetic changes that contribute to the current obesity epidemics. Hypothalamic proopiomelanocortin (POMC)-expressing neurons are crucial elements of energy balance, and its dysfunction cause severe obesity in experimental models and humans. Our hypothesis is that over nutrition causes epigenetic changes in POMC neurons that in turn lead to dysregulated energy homeostasis and obesity. The objective of this proposal is to establish for the first time a genome-wide epigenetic map of POMC neurons in the context of over nutrition during adulthood and fetal programming. To pursue this aim we will use an innovative cell-specific in vivo strategy to tag and reliably isolate POMC neurons, followed by next generation sequencing to evaluate chromatin accessibility and histone marks distribution across the genome. As a result, we will provide a novel framework for understanding the underlying epigenetic signatures related with obesity development and susceptibility. Hence, this project is in line with the Horizon 2020 Framework for improving our knowledge of the causes underlying a disease. Furthermore, the outcomes of this project may have potential therapeutic implications for the treatment of obesity since most epigenetic marks are reversible and therefore potentially targetable. The multidisciplinary nature of the project is strong, involving a combination of genetic engineering techniques, molecular biology and bioinformatics. This proposal includes the transfer of knowledge to the host institution and the training of the candidate in new techniques and transferable skills.