ArticleCell metabolism2017
The Glia-Neuron Lactate Shuttle and Elevated ROS Promote Lipid Synthesis in Neurons and Lipid Droplet Accumulation in Glia via APOE/D.
Article in Cell metabolism, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 356 papers.
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Who cites it
356 citing papers in PubMed, 555 citations in OpenAlex.
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- Age-dependent changes in lipid droplet distribution and vascularization in naked mole rat vs. mouse hippocampus.GeroScience · 2026Article
- Cholesterol maintains the degradative capacity of lysosomes during clearance and recycling of dysfunctional mitochondria.Nature communications · 2026Article
- Progressive behavioral and cognitive decline inbioRxiv : the preprint server for biology · 2026Article
- ENT1 inhibition links oligodendrocyte lipid metabolism to connectivity in tauopathy.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Epilepsy-associated digenic variants affecting an actin/mitochondria/glutamate pathway promote seizure susceptibility.The Journal of clinical investigation · 2026Article
- Opposing roles of DGAT-mediated lipid droplet biogenesis in the regulation of ferroptosis sensitivity.The FEBS journal · 2026Article
- Lipid droplets promote aberrant liquid-liquid phase separation of alpha-synuclein impairing energy homeostasis.EMBO reports · 2026Article
- APOEε4 attenuates early TREM2-mediated microglial responses and influences disease trajectories in dementia with Lewy bodies.Research square · 2026Article
- Interplay between N6-methyladenosine RNA methylation and protein lactylation: a novel crosstalk linking metabolism and epigenetic regulation in human diseases.Journal of translational medicine · 2026Review
- A lipid-binding protein that boosts daytime wake is mainly located at the body surface and blocks light-induced lipid peroxidation in the brain.Current biology : CB · 2026Article
- Review
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- Lactate alleviates early brain damage after subarachnoid hemorrhage: Regulation of lipid metabolism.Neural regeneration research · 2026Article
- Protocol for acute oxidative stress induction in third-instar Drosophila melanogaster larvae.STAR protocols · 2026Article
- An optimized method to visualize lipid droplets in mouse brain tissue.Cell reports methods · 2026Article
- CYP46A1 activation by low-dose efavirenz uncovers the link between brain cholesterol metabolism, energetics, and vasculature.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2026Article
- Lactylation and lactate: insights into muscle cell epigenetic regulators in exercise.Molecular medicine (Cambridge, Mass.) · 2026Review
- Article
296 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
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.
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