Dynamic Metabolome Analysis Reveals the Metabolic Fate of Medium-Chain Fatty Acids in AML12 Cells
Dynamic Metabolome Analysis Reveals the Metabolic Fate of Medium-Chain Fatty Acids in AML12 Cells
复制标题
DOI：
10.1021/acs.jafc.0c04723
复制
发表时间：
2020-10-23
影响因子：
6.1
通讯作者：
Bamba, Takeshi
中科院分区：
文献类型：
--
作者：
Fushimi, Tatsuya;Izumi, Yoshihiro;Bamba, Takeshi
一些肝细胞细胞系的研究报道了6-12碳的中链脂肪酸（MCFAs）与长链脂肪酸（LCFAs）表现出不同的代谢特性。然而，这些研究并未明确不同脂肪酸分子对肝细胞代谢的影响。本研究旨在捕捉在辛酸（FA 8:0）、癸酸（FA 10:0）或月桂酸（FA12:0）处理的AML12细胞中MCFA同化的代谢动力学[LCFA；油酸（FA 18:1）]通过代谢谱和c -13标记的动态代谢组分析。FA 8:0和FA 10:0处理的细胞培养液中总酮体浓度分别比FA 18:1处理的细胞培养液高3.22倍和3.69倍。与DMSO处理（对照组）相比，FA 12:0处理没有显著增加酮体水平，而FA 12:0处理使细胞内甘油三酯（TG）水平增加了15.4倍。FA 12:0处理样品的代谢谱与FA 8:0处理和FA 10:0处理样品的代谢谱不同，表明MCFA的代谢同化因MCFA类型的不同而有显著差异。此外，动态代谢组学分析清楚地表明，FA 8:0被快速定量氧化为乙酰辅酶a，并被同化为酮体、柠檬酸循环中间体和糖原氨基酸，但不易转化为tg。
Several studies in hepatocyte cell lines reported that medium-chain fatty acids (MCFAs) with 6-12 carbons showed different metabolic properties from long-chain fatty acids (LCFAs). However, these studies reported unclear effects of different fatty acid molecules on hepatocyte metabolism. This study is aimed to capture the metabolic kinetics of MCFA assimilation in AML12 cells treated with octanoic acid (FA 8:0), decanoic acid (FA 10:0), or lauric acid (FA12:0) [LCFA; oleic acid (FA 18:1)] via metabolic profiling and dynamic metabolome analysis with C-13-labeling. The concentrations of total ketone bodies in the media of cells treated with FA 8:0 or FA 10:0 were 3.22- or 3.69-fold higher than those obtained with FA 18:1 treatment, respectively. FA 12:0 treatment did not significantly increase ketone body levels compared to DMSO treatment (control), whereas FA 12:0 treatment increased intracellular triacylglycerol (TG) levels 15.4 times compared to the control. Metabolic profiles of FA 12:0treated samples differed from those of the FA 8:0-treated and FA 10:0-treated samples, suggesting that metabolic assimilation of MCFAs differed significantly depending on the MCFA type. Furthermore, the dynamic metabolome analysis clearly revealed that FA 8:0 was rapidly and quantitatively oxidized to acetyl-CoA and assimilated into ketone bodies, citrate cycle intermediates, and glucogenic amino acids but not readily into TGs.