Lipid and Lipoprotein Metabolism in Microglia

Microglia, once viewed as static bystanders with limited homeostatic functions, are now considered key players in the development of neuroinflammatory and neurodegenerative diseases. Microglial activation is a salient feature of neuroinflammation involving a dynamic process that generates multitudinous microglial phenotypes that can respond to a variety of situational cues in the central nervous system. Recently, a flurry of single cell RNA-sequencing studies have defined microglial phenotypes in unprecedented detail, and have highlighted robust changes in the expression of genes involved in lipid and lipoprotein metabolism. Increased expression of genes such as Apolipoprotein E (ApoE), Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) and Lipoprotein Lipase (LPL) in microglia during development, damage, and disease, suggest that increased lipid metabolism is needed to fuel protective cellular functions such as phagocytosis. This review describes our current understanding of lipid and lipoprotein metabolism in microglia, and highlights microglial lipid metabolism as a modifiable target for the treatment of neurodegenerative diseases such as Alzheimer’s disease and multiple sclerosis.