美国俄亥俄州立大学医学院的Deliang Guo研究小组发现，靶向DGAT1可通过增加脂肪代谢和氧化应激治疗胶质母细胞瘤。2020年6月18日，国际知名学术期刊《细胞—代谢》在线发表了这一成果。

研究人员发现，胶质母细胞瘤（GBM）上调二酰基甘油-酰基转移酶1（DGAT1），以将多余的游离脂肪酸（FA）存储到甘油三酸酯和脂质滴中。抑制DGAT1会破坏脂质稳态，并导致过多的FA进入线粒体进行氧化，从而导致高水平的活性氧（ROS）、线粒体损伤、细胞色素c释放和细胞凋亡。添加N-乙酰半胱氨酸或抑制FA穿梭进入线粒体可降低ROS和DGAT1抑制诱导的细胞死亡。研究人员在异种移植模型中显示，靶向DGAT1可阻止脂质液滴形成，诱导肿瘤细胞凋亡并显著抑制GBM生长。

总之，这项研究表明DGAT1上调可通过促进多余FA的储存来保护GBM免受氧化损伤并维持脂质稳态。靶向DGAT1可能是GBM的一种有前途的治疗方法。

据介绍，GBM是一种主要致死性脑瘤，它获取大量的FA以促进细胞生长。但是，癌症如何避免脂毒性尚不清楚。

附：英文原文

Title: Targeting DGAT1 Ameliorates Glioblastoma by Increasing Fat Catabolism and Oxidative Stress

Author: Xiang Cheng, Feng Geng, Meixia Pan, Xiaoning Wu, Yaogang Zhong, Chunyan Wang, Zhihua Tian, Chunming Cheng, Rui Zhang, Vinay Puduvalli, Craig Horbinski, Xiaokui Mo, Xianlin Han, Arnab Chakravarti, Deliang Guo

Issue&Volume: 2020-06-18

Abstract: Glioblastoma (GBM), a mostly lethal brain tumor, acquires large amounts of free fattyacids (FAs) to promote cell growth. But how the cancer avoids lipotoxicity is unknown.Here, we identify that GBM upregulates diacylglycerol-acyltransferase 1 (DGAT1) tostore excess FAs into triglycerides and lipid droplets. Inhibiting DGAT1 disruptedlipid homeostasis and resulted in excessive FAs moving into mitochondria for oxidation,leading to the generation of high levels of reactive oxygen species (ROS), mitochondrialdamage, cytochrome c release, and apoptosis. Adding N-acetyl-cysteine or inhibiting FA shuttling intomitochondria decreased ROS and cell death induced by DGAT1 inhibition. We show inxenograft models that targeting DGAT1 blocked lipid droplet formation, induced tumorcell apoptosis, and markedly suppressed GBM growth. Together, our study demonstratesthat DGAT1 upregulation protects GBM from oxidative damage and maintains lipid homeostasisby facilitating storage of excess FAs. Targeting DGAT1 could be a promising therapeuticapproach for GBM.

DOI: 10.1016/j.cmet.2020.06.002

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30303-X