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Unravelling the hypothalamic epigenetic code behind obesity.

Project description

The genetics behind obesity

Obesity is a huge healthcare problem worldwide and its prevalence has risen dramatically in the past four decades due to genetic predisposition, unhealthy diet, sedentary lifestyle, and more. Control of food intake is regulated by many neural and hormonal signals that interact with the central nervous system. The western diet is also associated with factors that contribute to current obesity epidemics. The EU-funded EPIOBESITY seeks to understand the underlying dynamics in obesity. Project outcomes may provide clues for developing targeted therapies for this metabolic disease that is slated to become the biggest cause of mortality in the near future.

Objective

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.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Call for proposal

(opens in new window) H2020-MSCA-IF-2018

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Coordinator

FUNDACIO DE RECERCA CLINIC BARCELONA-INSTITUT D INVESTIGACIONS BIOMEDIQUES AUGUST PI I SUNYER
Net EU contribution
€ 160 932,48
Address
CARRER ROSSELLO 149
08036 Barcelona
Spain
Region
Este Cataluña Barcelona
Activity type
Research Organisations
Links
Total cost
€ 160 932,48