Metabolic control of microglia in health and disease

Metabolic states within cells are tightly linked to functional outcomes and finely regulated by nutrient availability. A growing body of the literature supports the idea that various metabolites can influence cellular functions, such as cell differentiation, migration, and proliferation in different contexts, with ample evidence coming from the immune system. Additionally, certain functional programs can trigger significant metabolic changes within cells, which are crucial not only to meet high energy demands, but also to produce intermediate metabolites necessary to support specific tasks. Microglia, the resident innate immune cells of the central nervous system, are constantly active, surveying the brain parenchyma and providing support to neighboring cells in the brain. They exhibit high metabolic flexibility, capable of quickly undergoing metabolic reprogramming based on nutrient availability and functional requirements. In this chapter, we will discuss the major metabolic pathways within cells and provide examples of how relevant enzymes and metabolites can impact microglial function in physiologic and pathologic contexts.