Glutamate decreases oxidative stress and lipid droplet formation in astrocytes.

Astrocytes degrade fatty acids in response to glutamate while reducing the abundance of lipid droplets. But how glutamate regulates lipid droplets in astrocytes is unclear. Here, we used primary rat astrocytes to show that glutamate decreases the amount of reactive oxygen species, which, in turn, reduces autophagy and the amount of lipids in need of storage in lipid droplets. This decrease in lipid droplets and reactive oxygen species occurs independently of glutamate import through excitatory amino acid transporters (EAATs). However, activation of AMPK, downstream of EAATs, further promotes a decrease in lipid droplets. Glutamate also increases the pool of fused mitochondria capable of maintaining enhanced fatty acid metabolism. Our work reveals how astrocytic metabolism is regulated by glutamate, which can serve to coordinate astrocyte physiology with neuronal activity.