Damiano Fabrizio, De Benedetto Giuseppe E, Longo Serena, Giannotti Laura, Fico Daniela, Siculella Luisa, Giudetti Anna M
Department of Biological and Environmental Sciences and Technologies, University of Salento, Lecce, Italy.
Analytical and Isotopic Mass Spectrometry Laboratory, Department of Cultural Heritage, University of Salento, Lecce, Italy.
Front Neurosci. 2020 Jul 23;14:783. doi: 10.3389/fnins.2020.00783. eCollection 2020.
Medium-chain fatty acids (MCFA) are dietary components with a chain length ranging from 6 to 12 carbon atoms. MCFA can cross the blood-brain barrier and in the brain can be oxidized through mitochondrial β-oxidation. As components of ketogenic diets, MCFA have demonstrated beneficial effects on different brain diseases, such as traumatic brain injury, Alzheimer's disease, drug-resistant epilepsy, diabetes, and cancer. Despite the interest in MCFA effects, not much information is available about MCFA metabolism in the brain. In this study, with a gas chromatography-mass spectrometry (GC-MS)-based metabolomics approach, coupled with multivariate data analyses, we followed the metabolic changes of U87MG glioblastoma cells after the addition of octanoic (C8), or decanoic (C10) acids for 24 h. Our analysis highlighted significant differences in the metabolism of U87MG cells after the addition of C8 or C10 and identified several metabolites whose amount changed between the two groups of treated cells. Overall, metabolic pathway analyses suggested the citric acid cycle, Warburg effect, glutamine/glutamate metabolism, and ketone body metabolism as pathways influenced by C8 or C10 addition to U87MG cells. Our data demonstrated that, while C8 affected mitochondrial metabolism resulting in increased ketone body production, C10 mainly influenced cytosolic pathways by stimulating fatty acid synthesis. Moreover, glutamine might be the main substrate to support fatty acids synthesis in C10-treated cells. In conclusion, we identified a metabolic signature associated with C8 or C10 addition to U87MG cells that can be used to decipher metabolic responses of glioblastoma cells to MCFA treatment.
中链脂肪酸（MCFA）是一类饮食成分，其碳链长度为6至12个碳原子。MCFA能够穿过血脑屏障，在大脑中可通过线粒体β-氧化作用被氧化。作为生酮饮食的成分，MCFA已在不同脑部疾病中显示出有益作用，如创伤性脑损伤、阿尔茨海默病、耐药性癫痫、糖尿病和癌症。尽管人们对MCFA的作用很感兴趣，但关于其在大脑中的代谢情况却知之甚少。在本研究中，我们采用基于气相色谱-质谱联用（GC-MS）的代谢组学方法，并结合多变量数据分析，追踪了添加辛酸（C8）或癸酸（C10）24小时后U87MG胶质母细胞瘤细胞的代谢变化。我们的分析突出了添加C8或C10后U87MG细胞代谢的显著差异，并鉴定出两组处理细胞之间含量发生变化的几种代谢物。总体而言，代谢途径分析表明，柠檬酸循环、瓦伯格效应、谷氨酰胺/谷氨酸代谢和酮体代谢是受U87MG细胞添加C8或C10影响的途径。我们的数据表明，虽然C8影响线粒体代谢导致酮体生成增加，但C10主要通过刺激脂肪酸合成影响胞质途径。此外，谷氨酰胺可能是C10处理细胞中支持脂肪酸合成的主要底物。总之，我们确定了与U87MG细胞添加C8或C10相关的代谢特征，可用于解读胶质母细胞瘤细胞对MCFA治疗的代谢反应。
