Dynamic Metabolome Analysis Reveals the Metabolic Fate of Medium-Chain Fatty Acids in AML12 Cells

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.