TY - JOUR
T1 - Dynamic metabolome analysis reveals the metabolic fate of medium-chain fatty acids in AML12 cells
AU - Fushimi, Tatsuya
AU - Izumi, Yoshihiro
AU - Takahashi, Masatomo
AU - Hata, Kosuke
AU - Murano, Yoshihiro
AU - Bamba, Takeshi
N1 - Funding Information:
This study was partly supported by the AMED-CREST programs (20gm0910010h0205, 20gm0910013h0004, and 20gm1010010s0203) from the Japan Agency for Medical Research and Development (AMED) (to Y.I. and T.B.); a grant from the CREST Program (JPMJCR15G4) of the Japan Science and Technology Agency (JST) (to Y.I., and T.B.); a Grant-in-Aid for Scientific Research on Innovative Areas (17H06304) (to Y.I. and T.B.); and a Grant-in-Aid for Scientific Research (B) (18H01800) (to T.B.) and a Grant-in-Aid for Scientific Research (C) (19 K05167) (to Y.I.) from the Japan Society for the Promotion of Science (JSPS).
PY - 2020/10/28
Y1 - 2020/10/28
N2 - 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.
AB - 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.
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U2 - 10.1021/acs.jafc.0c04723
DO - 10.1021/acs.jafc.0c04723
M3 - Article
C2 - 33073987
AN - SCOPUS:85094932163
VL - 68
SP - 11997
EP - 12010
JO - Journal of Agricultural and Food Chemistry
JF - Journal of Agricultural and Food Chemistry
SN - 0021-8561
IS - 43
ER -