Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Johns Hopkins University, Baltimore, Maryland, USA.
Department of Mechanical & Industrial Engineering, University of Toronto, Toronto, Canada.
Sci Rep. 2019 Dec 20;9(1):19593. doi: 10.1038/s41598-019-55985-z.
Glioblastoma multiforme (GBM) is the most common and lethal primary malignant brain tumor in adults. Despite the multimodal standard treatments for GBM, the median survival is still about one year. Analysis of brain tissues from GBM patients shows that lipid droplets are highly enriched in tumor tissues while undetectable in normal brain tissues, yet the identity and functions of lipid species in GBM are not well understood. The aims of the present work are to determine how GBM utilizes fatty acids, and assess their roles in GBM proliferation. Treatment of U138 GBM cells with a monounsaturated fatty acid, oleic acid, induces accumulation of perilipin 2-coated lipid droplets containing triglycerides enriched in C18:1 fatty acid, and increases fatty acid oxidation. Interestingly, oleic acid also increases glucose utilization and proliferation of GBM cells. In contrast, pharmacologic inhibition of monoacylglycerol lipase attenuates GBM proliferation. Our findings demonstrate that monounsaturated fatty acids promote GBM proliferation via triglyceride metabolism, suggesting a novel lipid droplet-mediated pathway which may be targeted for GBM treatment.
多形性胶质母细胞瘤（GBM）是成人中最常见和最致命的原发性恶性脑肿瘤。尽管对 GBM 采用了多模式标准治疗，但中位生存期仍约为一年。对 GBM 患者脑组织的分析表明，脂滴在肿瘤组织中高度富集，而在正常脑组织中无法检测到，但 GBM 中脂质种类的身份和功能尚未得到很好的理解。本研究的目的是确定 GBM 如何利用脂肪酸，并评估它们在 GBM 增殖中的作用。用单不饱和脂肪酸油酸处理 U138 GBM 细胞会诱导富含 C18:1 脂肪酸的甘油三酯的 perilipin 2 包被脂滴的积累，并增加脂肪酸氧化。有趣的是，油酸还会增加 GBM 细胞的葡萄糖利用和增殖。相比之下，单酰基甘油脂肪酶的药理学抑制会减弱 GBM 的增殖。我们的研究结果表明，单不饱和脂肪酸通过甘油三酯代谢促进 GBM 增殖，提示可能针对 GBM 治疗的新型脂滴介导途径。
