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Regulation of hormone-sensitive lipase in neurons

Project description

Exploring neuronal lipid enzymes in brain function

Maintaining proper neuronal function and overall brain health depends on brain lipid regulation. Lipids and lipid-derived molecules serve as structural components of cell membranes, energy sources, and signalling molecules, influencing synaptic activity, cerebral blood flow and neuroinflammation. With the support of the Marie Skłodowska-Curie Actions programme, the RELINEU project focuses on the role of hormone-sensitive lipase (HSL), an enzyme known for mediating lipolysis in peripheral tissues. Recent findings reveal that HSL is abundant in neurons and synapses, and its genetic deletion in mice results in memory impairments under ageing and metabolic stress. The research team will investigate the regulation of neuronal HSL, its role in brain lipid metabolism and its implications for brain physiology.

Objective

Several lipids and lipid-derived molecules play crucial roles in regulating brain function, affecting synaptic activity and plasticity, cerebral blood flow regulation, and neuroinflammatory processes. Outside of the central nervous system, the hormone-sensitive lipase (HSL) mediates the actions of catecholamines, glucagon, and insulin on lipolysis. While HSL is present in the brain, its role in brain lipid metabolism remains unknown. Recent findings from the host lab demonstrate that HSL is abundant in neurons and enriched in synapses. Additionally, genetic deletion of HSL in mice leads to memory impairment when exposed to aging or metabolic stress (e.g. high-fat diet feeding). Suggested mechanisms by which HSL deletion leads to brain dysfunction include the production of eicosanoids and endocannabinoids, and control over energy metabolism and neurovascular coupling. However, the mechanisms regulating HSL activity in neurons remain unknown. We propose here that HSL is a relay between neuronal activity and the production of bioactive lipids that control brain physiology. This pioneering project aims to explore the physiological regulation of neuronal HSL and its neurophysiological implications in neuronal cells. The research will be conducted at Lund University, supervised by Dr. João Duarte, combining his expertise in brain metabolism and behavior with my background in biochemistry and cell biology. This project holds immense potential for advancing our understanding of brain lipid regulation and its relevance to brain function.

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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(opens in new window) HORIZON-MSCA-2023-PF-01

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Coordinator

LUNDS UNIVERSITET
Net EU contribution

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€ 222 727,68
Address
Paradisgatan 5c
22100 Lund
Sweden

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Region
Södra Sverige Sydsverige Skåne län
Activity type
Higher or Secondary Education Establishments
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Total cost

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