PROJECT: JTC2024 - Brain-Body: EMPATHY

Eating disorders are neuropsychiatric conditions characterised by severe and persistent disturbance in eating behaviours and associated distressing thoughts and emotions. Despite their individual and socio-economic burden, the aetiology of eating disorders is still poorly understood and suitable interventions are lacking. The risks for eating disorders are increased by the alterations of brain development in prenatal and perinatal period due to adverse maternal factors, such as unhealthy maternal diet and obesity. In particular, maternal high-fat diet affects the hypothalamus, the brain region involved in feeding control. Therefore, we aim to define how maternal metabolic programming during perinatal period disturbs the microglia-neuron interactions in the hypothalamus, increasing the risk of eating disorders in the offspring. We will employ both exploratory and hypothesis-driven approaches using a variety of models ranging from hiPSC-derived hypothalamic-like neurons and microglia as well as brain organotypic cultures, to Drosophila and mouse models. Finally, we will translationally validate the results obtained in animal models by examining the lipids and non-coding RNAs in human milk samples. Altogether, this interdisciplinary consortium will define molecular and cellular mechanisms of the development of eating disorders, contributing to our understanding of their aetiology and proposing possible targets as well as timing for risk-mitigating interventions.