Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), Tokyo, Japan; Ochadai Academic Production, Ochanomizu University, Tokyo, Japan.
Institute for Human Life Innovation, Ochanomizu University, Tokyo, Japan.
Brain Res. 2019 Dec 15;1725:146484. doi: 10.1016/j.brainres.2019.146484. Epub 2019 Sep 25.
Astrocytes exhibit an important role in neural lipid metabolism for the regulation of energy balance to supply fatty acids (FAs) and ketone bodies to other neural cells. Lipid droplets (LDs) consisting of neutral- and phospho-lipids increase in the brains of patients with neurodegenerative diseases, such as Alzheimer's disease and multiple sclerosis. However, the role of LDs and its lipid source remains largely unexplored. Here, we found that oleic acid (OA) was a potent inducer of astrocytic LD accumulation among various FAs. Lipidomic analysis using liquid chromatography equipped with tandem mass spectrometry revealed that the cellular triacylglycerol and phospholipid compositions in astrocytes during LD accumulation reflected the condition of extracellular FAs. Furthermore, the inhibition of diacylglycerol acyltransferase blocked OA-induced LD accumulation and caused lipotoxicity-induced cell death in astrocytes. The present study demonstrated that the formation of LDs, caused due to the increased extracellular OA, facilitated survival against lipotoxic condition.
星形胶质细胞在神经脂质代谢中发挥重要作用，以调节能量平衡，为其他神经细胞提供脂肪酸 (FAs) 和酮体。在神经退行性疾病患者的大脑中，如阿尔茨海默病和多发性硬化症，含有中性和磷酸脂质的脂滴 (LDs) 增加。然而，LDs 的作用及其脂质来源在很大程度上仍未得到探索。在这里，我们发现油酸 (OA) 是各种 FAs 中诱导星形胶质细胞 LD 积累的有效物质。使用配备串联质谱的液相色谱进行脂质组学分析表明，在 LD 积累期间，星形胶质细胞中的细胞三酰甘油和磷脂组成反映了细胞外 FAs 的情况。此外，二酰甘油酰基转移酶的抑制阻断了 OA 诱导的 LD 积累，并导致脂毒性诱导的星形胶质细胞死亡。本研究表明，由于细胞外 OA 的增加而形成的 LD 有助于对抗脂毒性条件下的存活。
