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Control of body weight by specialized brain-adipose loop neurons

Project description

A new era in understanding weight regulation’s complexities

Obesity is a problem worldwide because our bodies struggle to maintain the right energy balance. Current treatments often do not work well because our metabolism fights back. Additionally, we do not fully understand how our brains and fat cells communicate to regulate weight. With this in mind, the ERC-funded BrainLoops project will explore these brain circuits, hoping to find new ways to fight obesity. Specifically, it will study how the brain and fat cells talk to each other. Advanced techniques such as imaging and genetic tools will be used to observe the processes occurring. By understanding these connections better, they hope to develop treatments. This project could change how we think about weight and health.

Objective

Disruption of energy homeostasis can lead to obesity, a major health issue worldwide. Therapeutic efforts to reduce adiposity are nullified by metabolic adaptations. The mechanisms underlying these phenomena are unclear, precluding efficient intervention. Although it is well established that important hormonal factors control adiposity, it is less appreciated that fat (white adipose tissue, WAT) is innervated by sympathetic and sensory fibres forming, with discrete brain nuclei, loop circuits. These circuits are well-positioned for enabling WAT-brain bidirectional, non-hormonal communication, yet they remained uncharacterized.

This project will uncover the brain circuits processing sensory-sympathetic homeostatic control of body weight. Using labelling tracing strategies of the WAT, I will identify the brain areas containing loop neurons. I will interrogate their role in regulating body weight and processing WAT-derived inputs, using cutting-edge and complementary single-cell imaging and transcriptomic analysis. Complementarily, I will functionally manipulate, using opto- and chemo-genetics tools, the activity of loop neurons, and their brain→WAT outputs, in lean mice, mimicking activity changes in obesity, and assess system-wide effects on behavior, metabolism, and body weight.

My expertise in both central and peripheral systems gives me a unique perspective to address these fundamental questions. Uncovering the role of non-hormonal WAT-body communication in the regulation of energy homeostasis will revolutionise our understanding of weight regulation in health and disease. This project will identify new molecular targets to develop better therapeutic strategies for obesity while also creating a platform for synergy between brain circuits and body organs, facilitating a host of future advances and new research directions.

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2023-STG

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Host institution

KAROLINSKA INSTITUTET
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.

€ 1 499 521,00
Address
NOBELS VAG 5
171 77 STOCKHOLM
Sweden

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Region
Östra Sverige Stockholm Stockholms län
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.

€ 1 499 521,00

Beneficiaries (1)

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