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Development of hypothalamic circuits for the control of homeostasis

Project description

Childhood obesity and neuronal development

Obesity is a global burden, and childhood obesity is recognised as a major health problem. The EU-funded ONTOGENY project aims to discover the developmental processes important for the control of energy homeostasis. Hypothalamic agouti-related peptide (AgRP) neurons may stimulate food intake, while proopiomelanocortin (POMC) neurons inhibit feeding behaviour. The project will study the late ontogeny of AgRP and POMC neurons, measuring their activity during mouse development in response to nutrients and hormones involved in energy homeostasis. Ultimately, it will deliver important insights into AgRP and POMC neuron development in conditions relevant to childhood obesity and metabolic dysregulation.

Objective

Obesity is a significant global burden that is associated with adverse health outcomes. Adults are not alone in their struggles with obesity. Children now accumulate fat at an alarming rate, making childhood obesity a major health problem. Unfortunately, we do not know enough about the pathophysiology of these conditions to propose appropriate prevention strategies and more effective therapeutic approaches. In this ERC StG proposal, our goal is to discover the developmental processes important for proper con-trol of energy homeostasis. We will study Agrp and POMC neurons, located in the arcuate nucleus of the hypothalamus, that are heavily involved with control of energy homeostasis. Agrp and POMC neu-rons have delayed postnatal development, maturing their axonal projections around the third postnatal week in rodents. Here, we will study in detail this late ontogeny of Agrp and POMC neurons. In Aim 1, we will use novel approaches to measure Agrp and POMC neuronal activity during mouse development in response to nutrients and hormones involved in energy homeostasis. In Aim 2, we will use whole-brain imaging techniques to determine the anatomical development of Agrp and POMC neuronal projec-tions. We will also study the importance of a specific neuronal circuit in neonates to the development of obesity. Finally, in Aim 3, we will identify critical molecular mechanisms involved in the ontogeny of Agrp and POMC neurons by investigating their translatome over the course of postnatal development. Overall, this project will provide novel insights into Agrp and POMC neuron development in conditions relevant to childhood obesity and metabolic dysregulation. The functional, anatomical and molecular mechanisms illuminated here will provide the foundation for future studies aimed to dissect the devel-opment of other homeostatic systems.

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Keywords

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Programme(s)

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Topic(s)

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Funding Scheme

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ERC-STG - Starting Grant

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Call for proposal

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(opens in new window) ERC-2019-STG

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Host institution

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 1 999 973,00
Address
WELLINGTON SQUARE UNIVERSITY OFFICES
OX1 2JD Oxford
United Kingdom

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Region
South East (England) Berkshire, Buckinghamshire and Oxfordshire Oxfordshire
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 1 999 973,00

Beneficiaries (1)

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