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Cell. 2019 May 30;177(6):1522-1535.e14. doi: 10.1016/j.cell.2019.04.001. Epub 2019 May 23.

Neuron-Astrocyte Metabolic Coupling Protects against Activity-Induced Fatty Acid Toxicity.

Author information

1
Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA. Electronic address: ioannou@ualberta.ca.
2
Department of Physiology, University of Alberta, Edmonton, AB T6G 2H7, Canada; Neuroscience and Mental Health Institute, Edmonton, AB T6G 2E1, Canada.
3
Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA.
4
Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA. Electronic address: lippincottschwartzj@janelia.hhmi.org.
5
Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA. Electronic address: liuz11@janelia.hhmi.org.

Abstract

Metabolic coordination between neurons and astrocytes is critical for the health of the brain. However, neuron-astrocyte coupling of lipid metabolism, particularly in response to neural activity, remains largely uncharacterized. Here, we demonstrate that toxic fatty acids (FAs) produced in hyperactive neurons are transferred to astrocytic lipid droplets by ApoE-positive lipid particles. Astrocytes consume the FAs stored in lipid droplets via mitochondrial β-oxidation in response to neuronal activity and turn on a detoxification gene expression program. Our findings reveal that FA metabolism is coupled in neurons and astrocytes to protect neurons from FA toxicity during periods of enhanced activity. This coordinated mechanism for metabolizing FAs could underlie both homeostasis and a variety of disease states of the brain.

KEYWORDS:

ApoE; NMDA; astrocyte; fatty acid; lipid droplet; lipid peroxidation; lipoprotein particle; lipotoxicity; neuron; neuronal activity

PMID:
31130380
DOI:
10.1016/j.cell.2019.04.001

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