Neuron-Astrocyte Metabolic Coupling Protects against Activity-Induced Fatty Acid Toxicity
| Autor: | H. Amalia Pasolli, Shu-Hsien Sheu, Doreen Matthies, Song Pang, Jennifer Lippincott-Schwartz, Chi-Lun Chang, Zhe Liu, Harald F. Hess, Hui Liu, Aubrey V. Weigel, Jesse Jackson, Maria S. Ioannou, C. Shan Xu |
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| Rok vydání: | 2018 |
| Předmět: |
Male
Biology Lipoprotein particle General Biochemistry Genetics and Molecular Biology Lipid peroxidation Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Apolipoproteins E Lipid droplet medicine Premovement neuronal activity Animals Homeostasis 030304 developmental biology Mice Knockout Neurons 0303 health sciences Fatty Acids Brain Lipid metabolism Lipid Droplets Lipid Metabolism Cell biology Mitochondria Rats Mice Inbred C57BL medicine.anatomical_structure nervous system Lipotoxicity chemistry Astrocytes Neuron Oxidation-Reduction 030217 neurology & neurosurgery Astrocyte |
| Zdroj: | Cell. 177(6) |
| ISSN: | 1097-4172 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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