Project description DEENESFRITPL Maternal obesity as a potential cause of permanent changes in offspring's hypothalamic neurons Clinical and experimental studies show a correlation between obesity during pregnancy and congenital metabolic illnesses. Understanding the connection between maternal obesity and metabolic control deficits in the offspring requires an investigation of the hypothalamus as the neuroendocrine interface. The EU-funded FOODFORLIFE project is testing the hypothesis that maternal obesity causes permanent molecular changes in the offspring's hypothalamic neurons, damaging their plasticity and adaptive repertoire. The approach involves single-cell sequencing to discover permanent modifications to gene expression at the successive developmental stages in mouse models. The objective is to identify molecular, cellular and network-level changes in the hypothalamus of offspring born to obese mothers and to understand the life-long consequences of metabolic programming of the developing brain. Show the project objective Hide the project objective Objective Evolutionary success drives continuous human adaptation. A pervasive challenge is the substantial change in the composition and nutritional value of diets available. This is particularly relevant for child-bearing women because metabolic bias through diet composition can adversely affects pregnancy outcomes. Even though clinical and experimental studies correlate maternal obesity during pregnancy (affecting ~30% world-wide) with congenital metabolic illnesses, a causal relationship between maternal obesity, impairment in neuroendocrine development and ensuing deficits in metabolic control of affected offspring is as yet missing. The hypothalamus is the neuroendocrine interface linking the brain and periphery. Thus, we hypothesize that maternal obesity could evoke permanent molecular changes in hypothalamic neurons of the offspring to compromise their plasticity and adaptive repertoire. This notion is on the backdrop of our recent success in defining, by singe-cell RNA-seq and brain-wide imaging, the developmental trajectory of neurons that build the mammalian hypothalamus, and in discovering the function of novel neuronal subtypes. Here, we will determine molecular, cellular and network-level changes in the hypothalamus of offspring born to obese mothers. We will combine single-cell RNA-seq and ATAC-seq in the same neurons to precisely catalogue permanent modifications to gene expression at successive developmental stages in mice. We will particularly interrogate molecular determinants that can impair the neuronal circuitry controlling food intake, including leptin and endocannabinoid interplay as a candidate. We will complement these data by identifying novel cellular sites of hormone secretion that shape brain and bodily architecture and are sensitive to maternal obesity. Overall, our work will produce new understanding of the life-long consequences of metabolic programming of the developing brain. Fields of science medical and health sciencesclinical medicineobstetricsmedical and health scienceshealth sciencesnutritionobesity Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-2020-ADG - ERC ADVANCED GRANT Call for proposal ERC-2020-ADG See other projects for this call Funding Scheme ERC-ADG - Advanced Grant Coordinator MEDIZINISCHE UNIVERSITAET WIEN Net EU contribution € 2 498 960,00 Address Spitalgasse 23 1090 Wien Austria See on map Region Ostösterreich Wien Wien Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 Beneficiaries (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all MEDIZINISCHE UNIVERSITAET WIEN Austria Net EU contribution € 2 498 960,00 Address Spitalgasse 23 1090 Wien See on map Region Ostösterreich Wien Wien Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00
