The Glia-Neuron Lactate Shuttle and Elevated ROS Promote Lipid Synthesis in Neurons and Lipid Droplet Accumulation in Glia via APOE/D

• DOI: 10.1016/j.cmet.2017.08.024
• Publication Date: 2017-09-29T05:09:15Z
• Authors: Lucy Liu; Kevin R. MacKenzie; Nagireddy Putluri; Mirjana Maletić-S...; Hugo J. Bellen
• Keywords: Neuroglia; Lipid droplet; Apolipoprotein E

Elevated reactive oxygen species (ROS) induce the formation of lipids in neurons that are transferred to glia, where they form lipid droplets (LDs). We show glial and neuronal monocarboxylate transporters (MCTs), fatty acid transport proteins (FATPs), apolipoproteins critical for LD formation. MCTs enable glia secrete absorb lactate, which is converted pyruvate acetyl-CoA neurons. Lactate metabolites provide a substrate synthesis acids, processed by FATP apolipoproteins. In presence high ROS, inhibiting lactate transfer or lowering apolipoprotein levels decreases accumulation flies primary mouse glial-neuronal cultures. human APOE can substitute fly APOE4, an Alzheimer's disease susceptibility allele, impaired promotes neurodegeneration, providing insights into mechanisms.