Project description
Understanding sex differentiation in the brain leading to obesity
Obesity leads to about 1.6 million deaths annually, influenced by sex differences. In the brain, the hypothalamus regulates energy balance; disruptions can lead to obesity. Astrocytes supply energy to hypothalamic neurons, but it is unclear if nutritional challenges affect these cells differently by sex. Oestrogen signalling is key in sexual differentiation in the brain. Supported by the Marie Skłodowska-Curie Actions programme, the SHAPE project will explore oestrogen signalling in astrocytes and its role in hypothalamic adaptations to obesity and energy metabolism in lean and obese conditions. It will combine expertise in astrocyte biology and metabolic control to better understand the sex-dependent contributions of hypothalamic astrocytes to obesity development.
Objective
Obesity is a complex condition that causes around 1.6 million deaths each year. The metabolic alterations to an obesigenic environment are highly dependent on the sex of the individual. In the brain, the hypothalamus controls energy homeostasis by fine tuning feeding and energy expenditure to nutrient availability. Disruption of this regulation results in obesity. While hypothalamic neurons are crucial for the control of energy balance, their activity is tightly dependent on adequate delivery of energy substrates provided by astrocytes, the major type of glial cells in the brain. Whether nutritional challenges evoke sex-specific astrocyte adaptations and its contribution to the sex-dimorphism in the pathogenesis of obesity remains unknown. Interestingly, estrogen signaling is an essential target that mediates sexual differentiation in the brain. This project’s main aim is to determine the role of estrogen signaling in astrocytes in: 1) hypothalamic astrocytic adaptations to obesity, 2) energy metabolism in lean and obese conditions and 3) in the beneficial effects of incretin-based therapies against obesity. The present proposal intends to combine interdisciplinary expertise in astrocyte biology and neural control of metabolism to expand the understanding on the involvement of hypothalamic astrocytes in the development of obesity in a sex-dependent manner. The cutting-edge approach of ex vivo and in vivo astrocyte-selective targeting of estrogen signaling in specific hypothalamic areas, extends beyond the neuro-centrist approach by demonstrating that functional remodeling of hypothalamic astrocytes in response to nutrient overload represents a key step for the development of novel cell-selective therapeutic approaches for treating obesity and associated pathologies.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences basic medicine pathology
- medical and health sciences basic medicine physiology homeostasis
- medical and health sciences health sciences nutrition obesity
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-MSCA-2024-PF-01
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2333 ZA Leiden
Netherlands
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