Recently, lipid metabolism reprogramming has been further evidenced in malignancies via the observation of large amounts of lipid droplets (LDs) in human tumors, including in glioblastoma (GBM), the most lethal primary brain tumor. However, the role played by LDs in tumor cells remains unknown. Here, we show that triglycerides (TG), the major components of LDs, serve as a critical energy reservoir to support GBM cell survival. TG/LDs rapidly diminished in GBM cells upon glucose reduction, whereas inhibiting fatty acid oxidation or autophagy resulted in the accumulation of TG/LDs and strongly potentiated GBM cell death. Immunofluorescence imaging and time-lapse videos showed that LDs are hydrolyzed by autophagy to release free fatty acids that mobilize into mitochondria for energy production. Our study demonstrates that autophagy-mediated hydrolysis of TG/LDs maintains energy homeostasis and GBM survival upon glucose reduction, suggesting that limiting TG/LDs utilization might be necessary upon treating GBM.

最近，通过在人类肿瘤中观察到大量脂质滴（LDs），包括在最致命的原发性脑肿瘤胶质母细胞瘤（GBM）中，脂质代谢的重编程在恶性肿瘤中得到了进一步证明。然而，LDs在肿瘤细胞中所起的作用仍然未知。在这里，我们表明甘油三酯（TG），LDs的主要成分，作为支持GBM细胞存活的关键能量库。葡萄糖还原后，GBM细胞中的TG / LDs迅速减少，而抑制脂肪酸氧化或自噬导致TG / LDs的积累并强烈增强了GBM细胞的死亡。免疫荧光成像和延时录像显示，LDs通过自噬被水解，释放出游离脂肪酸，该游离脂肪酸动员到线粒体中以产生能量。