Microglia Lipid Droplets in Physiology and Neurodegeneration

Lipid droplets (LDs) are dynamic organelles found in organisms ranging from yeast to humans. Originally thought of as inert lipid-storing structures, a growing body of research suggests LDs have roles beyond supplying lipids for metabolism and membrane expansion. Lipid droplets are present under normal physiological conditions in certain cell types, such as hepatocytes and adipocytes. In these metabolically active cells, LDs are thought to primarily serve as lipid reservoirs (Walther and Farese, Annu Rev Biochem 81:687–714, 2012). In other cell types, such as macrophages and glia, lipid droplets primarily form under pathological conditions. For instance, macrophages form lipid laden foam cells during atherosclerosis, and microglia, which are brain resident macrophages, accumulate lipid droplets in many neurodegenerative diseases (Ralhan et al., J Cell Biol 220:e202102136, 2021; Gutierrez, Arq Bras Cardiol 119:542–543, 2022). Understanding the roles of lipid droplets across cell types in health and disease is an area of active research. The focus of this book chapter is to provide a brief overview of general lipid droplet biology followed by a discussion on our current knowledge of the formation and function of lipid droplets in microglia.