RELINEU · Regulation of hormone-sensitive lipase in neurons

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.