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 13C-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 12:0-treated 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.