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

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Neuron-Astrocyte Metabolic Coupling Protects against Activity-Induced Fatty Acid Toxicity.
Cell ( IF 45.5 ) Pub Date : 2019-05-23 , DOI: 10.1016/j.cell.2019.04.001
Maria S Ioannou ₁ , Jesse Jackson ₂ , Shu-Hsien Sheu ₁ , Chi-Lun Chang ₁ , Aubrey V Weigel ₁ , Hui Liu ₁ , H Amalia Pasolli ₁ , C Shan Xu ₁ , Song Pang ₁ , Doreen Matthies ₁ , Harald F Hess ₁ , Jennifer Lippincott-Schwartz ₁ , Zhe Liu ₁

Affiliation

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.

中文翻译：

神经元-星形胶质细胞代谢偶联可防止活动诱导的脂肪酸毒性。

神经元和星形胶质细胞之间的代谢协调对于大脑的健康至关重要。然而，脂质代谢的神经元-星形细胞偶联，特别是对神经活动的应答，在很大程度上仍未表征。在这里，我们证明在ApoE阳性脂质颗粒中，在过度活跃的神经元中产生的有毒脂肪酸（FAs）被转移到星形胶质液滴上。星形胶质细胞响应于神经元活性，通过线粒体β-氧化消耗脂质滴中储存的FA，并启动解毒基因表达程序。我们的发现表明，FA代谢在神经元和星形胶质细胞中耦合，以在活动增强期间保护神经元免受FA毒性。这种代谢FA的协调机制可能是体内稳态和大脑多种疾病状态的基础。

更新日期：2019-05-23

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