Lipid metabolism, remodelling and intercellular transfer in the CNS

Lipid metabolism encompasses the catabolism and anabolism of lipids, and is fundamental for the maintenance of cellular homeostasis, particularly within the lipid-rich CNS. Increasing evidence further underscores the importance of lipid remodelling and transfer within and between glial cells and neurons as key orchestrators of CNS lipid homeostasis. In this Review, we summarize and discuss the complex landscape of processes involved in lipid metabolism, remodelling and intercellular transfer in the CNS. Highlighted are key pathways, including those mediating lipid (and lipid droplet) biogenesis and breakdown, lipid oxidation and phospholipid metabolism, as well as cell-cell lipid transfer mediated via lipoproteins, extracellular vesicles and tunnelling nanotubes. We further explore how the dysregulation of these pathways contributes to the onset and progression of neurodegenerative diseases, and examine the homeostatic and pathogenic impacts of environment, diet and lifestyle on CNS lipid metabolism.