Open Close
Reference
Citation
Liu, L., MacKenzie, K.R., Putluri, N., Maletić-Savatić, M., Bellen, H.J. (2017). The Glia-Neuron Lactate Shuttle and Elevated ROS Promote Lipid Synthesis in Neurons and Lipid Droplet Accumulation in Glia via APOE/D.  Cell Metab. 26(5): 719--737.e6.
FlyBase ID
FBrf0237138
Publication Type
Research paper
Abstract

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

Graphical Abstract
Obtained with permission from Cell Press.
PubMed ID
PubMed Central ID
PMC5677551 (PMC) (EuropePMC)
Related Publication(s)
Personal communication to FlyBase

Additional constructs and insertions related to Liu et al 2017.
Bellen, 2017.11.14, Additional constructs and insertions related to Liu et al 2017. [FBrf0237394]

Note

Glial Cell Evolution: The Origins of a Lipid Store.
Nave et al., 2017, Cell Metab. 26(5): 701--702 [FBrf0237215]

Associated Information
Comments
Associated Files
Other Information
Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Cell Metab.
    Title
    Cell Metabolism
    Publication Year
    2005-
    ISBN/ISSN
    1550-4131
    Data From Reference
    Alleles (42)
    Genes (19)
    Human Disease Models (5)
    Natural transposons (2)
    Insertions (8)
    Experimental Tools (2)
    Transgenic Constructs (31)
    Transcripts (1)