Neuron-astrocyte metabolic coupling protects against activity-induced fatty acid toxicity.

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

Neuron-astrocyte metabolic coupling protects against activity-induced fatty acid toxicity. Hess LabLippincott-Schwartz LabLiu (Zhe) Lab

Ioannou MS, Jackson J, Sheu S, Chang C, Weigel AV, Liu H, Pasolli HA, Xu CS, Pang S, Matthies D, Hess HF, Lippincott-Schwartz J, Liu Z

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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.

PMID: 31130380 [PubMed - indexed for MEDLINE]

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Neuron-astrocyte metabolic coupling protects against activity-induced fatty acid toxicity.

Abstract

PMID: 31130380 [PubMed - indexed for MEDLINE]

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